The Stressed CNS: When Glucocorticoids Aggravate Inflammation
Open accessAbstract
Glucocorticoids (GCs) are hormones released during the stress response that are well known for their immunosuppressive and anti-inflammatory properties; however, recent advances have uncovered situations wherein they have effects in the opposite direction. The CNS is a particularly interesting example, both because of its unique immune environment, and because GCs affect immune responses differently in different brain regions. In this minireview we discuss the contexts wherein GCs increase CNS inflammation and point out directions for future investigation.
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- Premisecitation
Subacute stress induces GR-dependent microglia proliferation.
“indeed subacute stress induces GR-dependent microglia proliferation (Nair and Bonneau, 2006)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Nair and Bonneau, 2006
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- Premisecitation
In the periphery, acute stress 24 hr prior to LPS treatment augments LPS-induced increases in plasma levels of IL-1β, TNF-α, and IL-6.
“For example, acute stress 24 hr prior to lipopolysaccharide (LPS) treatment augments LPS-induced increases in plasma levels of IL-1β, TNF-α, and IL-6 (Johnson et al., 2002).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Johnson et al., 2002 source
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- Premisecitation
CORT decreases glucose transport into neurons and glia in the hippocampus.
“One mechanism to explain these endangering effects of CORT is that the hormone decreases glucose transport into neurons and glia in the hippocampus.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sapolsky, 1999 source
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- Premisecitation
Glucocorticoids decrease immune activation via protein-protein interactions between GR and NF-κB in the nucleus.
“GCs also decrease immune activation via protein-protein interactions between GR and NF-κB in the nucleus (Figure 1) (De Bosscher et al., 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites De Bosscher et al., 2003 source
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- Premisecitation
In the absence of injury, acute stress can activate inflammatory mediators in the CNS.
“In the absence of injury, acute stress can activate inflammatory mediators in the CNS.”
Quote in the paperSubstantial claim
- Interpretationreasoning
GC-augmented inflammation may contribute to the endangerment of neurons by glucocorticoids.
“GC-augmented inflammation may also contribute to this endangerment.”
- Also stated in: § Functional Implications: GCs Endanger Injured Neurons · hedged
“The former conclusion is likely because GCs can augment LPS-induced CNS inflammation in the absence of neuronal death.”
Quote in the paperSubstantial claim - Also stated in: § Functional Implications: GCs Endanger Injured Neurons · hedged
- Premisecitation
Impaired CORT secretion is implicated in several autoimmune disorders.
“indeed, impaired CORT secretion is implicated in several autoimmune disorders (Wick et al., 1993).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wick et al., 1993
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- Premisecitation
In the periphery, acute stress post-LPS decreases the production of IL-1β, TNF-α, and IL-6.
“By contrast, acute stress post-LPS decreases the production of these same cytokines (Goujon et al., 1995).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Goujon et al., 1995 source
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- Premisecitation
Microglia extracted from CORT pretreated rats and challenged ex vivo with LPS upregulate MHCII and TLR-4 and produce more IL-1β and TNF-α than microglia from control rats.
“Microglia are important in this response because when they are extracted from CORT pretreated rats and challenged ex vivo with LPS, they upregulate MHCII and toll-like receptor-4 (TLR-4) and produce more IL-1β and TNF-α than microglia extracted from control rats do (Frank et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Frank et al., 2009
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- Premisecitation
MAPK (ERK and JNK) can decrease GR nuclear transport and affinity to cofactors via phosphorylation.
“Reciprocally, MAPK (ERK and JNK) can decrease GR nuclear transport and affinity to cofactors via phosphorylation (Rogatsky et al., 1998).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rogatsky et al., 1998 source
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- Premisecitation
Proinflammatory stimuli such as LPS induce MKP-1 expression, creating a negative feedback loop that downregulates production of TNF-α, IL-1β, and IL-6.
“Proinflammatory stimuli such as LPS also induce MKP-1 expression, creating a negative feedback loop that downregulates production of TNF-α, IL-1β, and IL-6 (Zhao et al., 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Zhao et al., 2005 source
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- Premisecitation
At least some of the stress effects on CNS inflammatory mediators are GC dependent and GR mediated.
“At least some of these stress effects are GC dependent and GR mediated (Garcia-Bueno et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Garcia-Bueno et al., 2008 source
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- Interpretationreasoning
Glucocorticoids can augment LPS-induced CNS inflammation in the absence of neuronal death.
“The former conclusion is likely because GCs can augment LPS-induced CNS inflammation in the absence of neuronal death.”
Quote in the paperSubstantial claim - Premisecitation
GC signaling via GR makes neurons, most notably in the hippocampus, less capable of surviving a variety of insults.
“Numerous studies demonstrate that GC signaling via GR makes neurons (most notably in the hippocampus) less capable of surviving a variety of insults.”
Quote in the paperSubstantial claim - Premisecitation
Acute stress directs leukocytes to leave circulation and relocate to tissues where they might be needed.
“Instead, acute stress directs these cells to leave circulation and relocate to the tissues where they might be needed, a redeployment from the “barracks” to the “battle stations” (McEwen et al., 1997).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites McEwen et al., 1997 source
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- Premisecitation
Prior acute stress worsens stroke damage by increasing IL-1β levels in the postischemic cortex.
“As evidence, prior acute stress worsens stroke damage by increasing IL-1β levels in the postischemic cortex (Caso et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Caso et al., 2007 source
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- Premisecitation
In humans, plasma levels of TNF-α and IL-6 are higher if cortisol is given 12 hr prior to, but not concurrent with, LPS.
“In humans, plasma levels of TNF-α and IL-6 are higher if cortisol is given 12 hr prior to, but not concurrent with, LPS (Barber et al., 1993).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Barber et al., 1993 source
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- Premisecitation
In one study, chronic stress occurred after injury but still increased LPS-induced TNF-α expression and microglia activation.
“Importantly, in this study, chronic stress occurred after the injury, but still increased LPS-induced TNF-α expression and microglia activation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites de Pablos et al., 2006 source
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- Interpretationreasoning
Whether glucocorticoids increase or decrease CNS inflammation depends on the dose, timing, duration of GC exposure, and the type of GC.
“Whether GCs increase or decrease CNS inflammation depends on the dose, timing, duration of GC exposure, and the type of GC”
Quote in the paperSubstantial claim - Premisecitation
In the CNS, CORT diminishes the expression of IL-1β and TNF-α when given 1 hr post LPS.
“By contrast, CORT diminishes the expression of these same cytokines when given 1 hr post LPS.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Frank et al., 2009
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- Premisecitation
Chronic exposure to glucocorticoids, particularly synthetic glucocorticoids at supra-physiological levels, inhibits both innate and adaptive immunity.
“Moreover, chronic exposure to GCs (particularly synthetic GCs at supra-physiological levels) inhibits both innate and adaptive immunity.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites De Bosscher et al., 2003 source
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- Premisecitation
Prior CORT exposure primes cytokine release from microglia ex vivo.
“and prior CORT exposure primes cytokine release from microglia ex vivo (Frank et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Frank et al., 2006 source
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- Premisecitation
Adrenoceptor antagonists inhibit stress-induced increases in CNS cytokine production.
“Supporting this conclusion, adrenoceptor antagonists inhibit stress-induced increases in CNS cytokine production (Johnson et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Johnson et al., 2005 source
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- Interpretationcitation
Glucocorticoids affect immune responses differently in different brain regions.
“GCs affect immune responses differently in different brain regions.”
- Also stated in: § Brain Regional Differences in GC Effects · plain
“There are also brain regional differences in how GCs modulate the inflammatory response to LPS.”
Quote in the paperSubstantial claim - Also stated in: § Brain Regional Differences in GC Effects · plain
- Premisecitation
Subacute CORT treatment increases inflammatory cell recruitment and cytokine production at an excitotoxic injury site.
“Subacute CORT treatment increases inflammatory cell recruitment and cytokine production at an excitotoxic injury site (Dinkel et al., 2003).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Dinkel et al., 2003 source
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- Premisecitation
Chronic stress increases both neuronal death and astrocytic death in a GR-dependent manner after direct LPS injection into the cortex.
“Finally, chronic stress increases both neuronal death and astrocytic death in a GR-dependent manner after direct LPS injection into the cortex (de Pablos et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites de Pablos et al., 2006 source
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- Premisecitation
Animals with higher basal CORT levels have a greater accumulation of proinflammatory mediators.
“Moreover, animals with higher basal CORT levels have a greater accumulation of proinflammatory mediators (Perez-Nievas et al., 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Perez-Nievas et al., 2007 source
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- Premisecitation
Glucocorticoids increased inflammatory cell infiltration prior to the emergence of neuronal death.
“This was seen in one study where GCs increased inflammatory cell infiltration prior to the emergence of neuronal death (Dinkel et al., 2003).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Dinkel et al., 2003 source
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- Premisecitation
In the CNS, CORT given prior to LPS challenge increases IL-1β and TNF-α expression in the hippocampus.
“CORT given prior to LPS challenge increases IL-1β and TNF-α expression in the hippocampus (Frank et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Frank et al., 2009
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- Interpretationreasoning
Glucocorticoid actions can exacerbate injury-induced neuronal death.
“these GC actions can exacerbate injury-induced neuronal death.”
Quote in the paperSubstantial claim - Interpretationcitation
Acute stress or CORT exposure can prime a subsequent inflammatory response, making it greater.
“If stress occurs prior to immune activation, it can have a “priming” effect that makes the subsequent response greater.”
Quote in the paperSubstantial claim - Premisecitation
Acute glucocorticoid exposure induces sustained expression of MKP-1 in a variety of cells including macrophages.
“Acute GC exposure induces sustained expression of MKP-1 in a variety of cells including macrophages (Roger et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Roger et al., 2005 source
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- Premisecitation
In the frontal cortex, GR signaling is essential for chronic stress to increase LPS-induced activation of several components of the MAPK signaling pathway involved in activating NF-κB.
“Supporting these results, in the frontal cortex, GR signaling is essential for chronic stress to increase LPS-induced activation of several components of the MAPK signaling pathway involved in activating NF-κB (de Pablos et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites de Pablos et al., 2006 source
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- Premisereasoning
The balance between NF-κB and GR signaling is important in predicting glucocorticoid actions.
“In addition to GR phosphorylation, the balance between NF-κB and GR signaling is important in predicting GC actions.”
Quote in the paperSubstantial claim - Premisenone given
GR activation is required for chronic-stress-augmented NF-κB activation.
“As discussed, GR activation is required for chronic-stress-augmented NF-κB activation”
Quote in the paperNot a substantial claim - Premisecitation
Different GR domains are responsible for NF-κB and AP-1 interactions.
“This role may not be the same as that for NF-κB because different GR domains are responsible for NF-κB and AP-1 interactions (Bladh et al., 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bladh et al., 2005 source
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- May combine two claims. 13
- Classified as probably not a substantial claim. 1
May combine two claims.
InterpretationreasoningBoth glucocorticoids and stress can augment aspects of inflammation in the CNS in a GC- and GR-dependent manner.
“Both GCs and stress (in a GC-and GR-dependent manner) can augment aspects of inflammation in the CNS”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningGlucocorticoids are not uniformly anti-inflammatory; they can have pro-inflammatory effects in some situations, including in the injured CNS.
“As the key point, a class of stress hormones renowned for their capacity to suppress inflammation often fails to do so, and can even worsen inflammation in the injured CNS.”
- Also stated in: § Conclusions · plain
“GCs, while renowned for their anti-inflammatory actions, are not uniformly anti-inflammatory, including in the context of CNS inflammation.”
Quote in the paperSubstantial claim- Also stated in: § Conclusions · plain
May combine two claims.
PremisecitationBasal CORT levels induce SHIP1, which increases NF-κB activation by inhibiting AKT.
“Basal CORT levels induce SHIP1, which increases NF-κB activation by inhibiting AKT (Zhang and Daynes, 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Zhang and Daynes, 2007
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Classified as probably not a substantial claim.
PremisecitationCORT secretion during stress mediates recovery from the initial immune activation.
“This led to the theory that CORT secretion during stress actually mediates recovery from this initial immune activation (Munck et al., 1984).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Munck et al., 1984 source
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PremisecitationSubacute CORT treatment worsens CA1 hippocampal neuron loss caused by global ischemia and CA3 neuron loss caused by excitotoxins.
“For example, subacute CORT treatment worsens CA1 hippocampal neuron loss caused by global ischemia (Sapolsky and Pulsinelli, 1985) and CA3 neuron loss caused by excitotoxins (Dinkel et al., 2003).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Sapolsky and Pulsinelli, 1985
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- cites Dinkel et al., 2003 source
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PremisecitationSubacute stress induces an increase in TNF-α levels in the cortex, and blocking this increase lessens stroke damage.
“Moreover, subacute stress induces an increase in TNF-α levels in the cortex, and blocking this increase lessens stroke damage (Caso et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Caso et al., 2006 source
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Premisenone givenHigher levels of CORT antagonize MAPK signaling by inducing expression of MKP-1, which reduces NF-κB activation.
“Higher levels of CORT antagonize MAPK signaling by inducing expression of MAPK phosphatase-1 (MKP-1), which reduces NF-κB activation.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationAcute stress increases NF-κB activity, intracellular TNF-α-convertase activity, extracellular TNF-α, and prostaglandin E2 and COX-2 levels in the cortex.
“Acute stress increases NF-κB activity (Madrigal et al., 2001), intracellular TNF-α-convertase activity, extracellular TNF-α (Madrigal et al., 2002), and prostaglandin E2 and COX-2 levels (Madrigal et al., 2003) in the cortex.”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationChronic glucocorticoid exposure reduces circulating leukocyte counts and decreases the production of proinflammatory cytokines including IL-1β and TNF-α.
“For example, chronic GC exposure reduces circulating leukocyte counts and decreases the production of a large variety of proinflammatory cytokines including IL-1β and TNF-α (De Bosscher et al., 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites De Bosscher et al., 2003 source
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PremisecitationIn cultured macrophages, CORT treatment 24 or 12 hr prior to LPS increases LPS-induced TNF-α, IL-6, and nitrite levels, while CORT treatment at 6, 3, or 0 hr prior to LPS does not.
“Similarly, in cultured macrophages, CORT treatment 24 or 12 hr prior to LPS increases LPS-induced TNF-α, IL-6, and nitrite levels, while CORT treatment at 6, 3, or 0 hr prior to LPS does not (Smyth et al., 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Smyth et al., 2004 source
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PremisecitationGR activation during chronic stress increases LPS-induced NF-κB activation and TNF-α, IL-1β, and iNOS expression in the hippocampus and frontal cortex, but has opposite effects in the hypothalamus.
“For example, GR activation during chronic stress increases LPS-induced NF-κB activation and TNF-α, IL-1β, and iNOS expression in the hippocampus and frontal cortex, but has opposite effects in the hypothalamus (Munhoz et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Munhoz et al., 2006 source
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PremisecitationBasal levels of CORT are required for the synthesis of epinephrine in the adrenals and for proper norepinephrine signaling.
“CORT plays a role in this immune activation as well because basal levels of CORT are required for the synthesis of E in the adrenals (Wurtman and Axelrod, 1966) and for proper NE signaling (Joels and de Kloet, 1989).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Wurtman and Axelrod, 1966
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- cites Joels and de Kloet, 1989 source
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PremisecitationWidespread use of glucocorticoids in clinical neurology to control CNS inflammation and poststroke edema is often ineffective and can even worsen clinical outcome.
“While there is widespread use of GCs in clinical neurology to control CNS inflammation in general and poststroke edema in particular, such interventions are often ineffective and can even worsen clinical outcome (Gomes et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gomes et al., 2005 source
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PremisecitationDEX can decrease human monocyte expression of many anti-inflammatory genes while simultaneously increasing expression of a number of proinflammatory chemokines, complement proteins, and cytokines.
“In one study, microarray profiling demonstrates that while DEX can decrease human monocyte expression of many anti-inflammatory genes, it simultaneously increases the expression of a number of proinflammatory chemokines, complement proteins, and cytokines (Galon et al., 2002).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Galon et al., 2002 source
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The paper relies on this without support.
Findings from animal models of CNS inflammation and injury are relevant to human clinical neurology.
“Because of the obvious clinical implications of these findings, it is imperative to determine how GCs affect CNS inflammation, particularly when they make it worse.”
The paper relies on this without support.
LPS-induced CNS inflammation is a valid model for injury-induced CNS inflammation.
“Until now we have primarily considered situations wheren inflammation occurs in the absence of neuronal death (i.e., after LPS administration).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Excess cortisol may increase binding to mineralocorticoid receptors, which can produce a pro-inflammatory response.
“Additionally, excess cortisol may increase the binding to Mineralocorticoid Receptors that can produce a pro-inflammatory response [23,24].”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [23]
In “An Introduction to Glucocorticoids and the Stress Response” (page unavailable), the paper says mineralocorticoid receptors are already heavily occupied at basal CORT levels; moderate to severe stress instead heavily occupies glucocorticoid receptors. Although the paper describes circumstances in which CORT enhances inflammation, it does not attribute that response to increased mineralocorticoid-receptor binding from excess cortisol. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThis may lead to sustained production of pro-inflammatory cytokines like IL-6 and TNF-α.
“This may lead to sustained production of pro-inflammatory cytokines like IL-6 and TNF-α [23].”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [23]
The section “Acute CORT Exposure Primes a Subsequent Inflammatory Response” reports increased TNF-α and IL-6 after stress or CORT exposure before an LPS challenge. It does not establish sustained production of those cytokines; the reported increases depend on the timing of exposure and the inflammatory challenge. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measured
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Novel glucocorticoid effects on acute inflammation in the CNS
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Induction of cyclooxygenase-2 accounts for restraint stress-induced oxidative status in rat brain
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Crosstalk between glucocorticoids and mitogen-activated protein kinase signalling pathways
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The role of tumor necrosis factor-alpha in stress-induced worsening of cerebral ischemia in rats
Caso, J. R., Lizasoain, I., Lorenzo, P., Moro, M. A., & Leza, J. C. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.06.009 · Cited by 45 · see citing works
Self-citationSapolsky, R. M. (2004) · Cited by 22 · see citing works
Self-citation
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Coutinho, A. E., & Chapman, K. E. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.04.005 · Cited by 1,815 · see citing works
“This was true in both the brain and the liver, raising the possibility that chronic hypothalamic–pituitary–adrenal (HPA) axis activation (as may occur during chronic inflammation for example) exaccerbates inflammation in the brain and elsewhere (reviewed in Sorrells et al. (2009)).”
Towards a glutamate hypothesis of depression
Sanacora, G., Treccani, G., & Popoli, M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.07.036 · Cited by 1,036 · see citing works
“…response is a complex physiological mechanism and, although much of this mechanism has been unveiled in recent years (de Kloet et al., 2005; McEwen, 2010; Sorrells et al., 2009), the way whereby an incorrect stress response is linked to pathophysiology is still far from being completely understood.”
BackgroundPenninx, B. W., Milaneschi, Y., Lamers, F., & Vogelzangs, N. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-129 · Cited by 839 · see citing works
“However, the relationship between HPA-activation and its effect on inflammation is extremely complex; whether glucocorticoids increase or decrease inflammation may depend on factors such as dose, duration and timing of glucocorticoids exposure and the brain area involved [134].”
BackgroundInflammation: The Common Pathway of Stress-Related Diseases
Liu, Y.-Z., Wang, Y.-X., & Jiang, C.-L. (2017) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2017.00316 · Cited by 800 · see citing works
“Four-week chronic stress exposure significantly upregulates the inflammatory cytokines such as TNFα, IL-18, IL-1β and inflammatory inducible NOS (iNOS) expression (Peng et al., 2012).”
BackgroundInfluentialThe neurobiology of depression: An integrated view
Dean, J., & Keshavan, M. (2017) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2017.01.025 · Cited by 765 · see citing works
Neuropathogenesis of Delirium: Review of Current Etiologic Theories and Common Pathways
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Sex differences in stress-related psychiatric disorders: neurobiological perspectives
Bangasser, D. A., & Valentino, R. J. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.03.008 · Cited by 737 · see citing works
“Appropriate glucocorticoid negative feedback is critical because the metabolic and immune changes induced by glucocorticoid release that are adaptive in the short term, are detrimental to health if they endure [29; 49; 50].”
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Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure
Maldonado, J. R. (2018) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4823 · Cited by 617 · see citing works
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“…activity by priming heightened inflammatory reactivity, stimulating immune cell trafficking, and promoting glucocorticoid insensitivity/resistance (Sorrells et al. 2009). www.annualreviews.org • Social Safety Theory 271 Social signal transduction: process by which neurocognitive representations…”
BackgroundThe HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain
Bellavance, M.-A., & Rivest, S. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00136 · Cited by 419 · see citing works
Stress and the brain: Individual variability and the inverted-U
Sapolsky, R. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4109 · Cited by 413 · see citing works
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“have other effects in the brain (Sorrells et al., 2009).”
Palma-Gudiel, H., Córdova-Palomera, A., Leza, J. C., & Fañanás, L. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.016 · Cited by 347 · see citing works
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The role of neuroimmune signaling in alcoholism
Crews, F. T., Lawrimore, C. J., Walter, T. J., & Coleman, L. G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.031 · Cited by 321 · see citing works
“Intriguingly, glucocorticoids have pro-inflammatory effects under the right circumstances (Sorrells et al., 2009).”
The mouse that roared: neural mechanisms of social hierarchy
Wang, F., Kessels, H. W. H. G., & Hu, H. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.07.005 · Cited by 261 · see citing works
Neuroinflammation and neurodegeneration in overnutrition-induced diseases
Cai, D. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.11.003 · Cited by 256 · see citing works
Sierra, A., Beccari, S., Díaz‐Aparicio, I., Encinas, J. M., Comeau, S., & Tremblay, M. (2014) · Neural Plasticity · doi:10.1155/2014/610343 · Cited by 249 · see citing works
“In contrast, glucocorticoids are considered to be proinflammatory in the chronically stressed brain [81], where among other changes they can promote inflammation, oxidative stress, neurodegeneration, andmicroglial activation [82].”
BackgroundToll-like receptors in chronic pain
Nicotra, L. L., Loram, L. C., Watkins, L. R., & Hutchinson, M. R. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.09.038 · Cited by 250 · see citing works
“The concept of rebound proinflammatory effects of glucocorticoid administration (Frank, et al., 2007; Sorrells et al., 2009; Sorrells and Sapolsky, 2007) has recently been extended to pain, where prior glucocorticoids potentiated mechanical allodynia induced by LPS (Loram, et al., 2011 “in press”).”
BackgroundTian, R., Hou, G., Li, D., & Yuan, T. (2014) · The Scientific World JOURNAL · doi:10.1155/2014/780616 · Cited by 237 · see citing works
“These inconsistencies are suggested to be results of the type, duration and intensity of stressors, detection methods, and individual differences [3, 33].”
BackgroundRos-Bernal, F., Hunot, S., Herrero, M. T., Parnadeau, S., Corvol, J.-C., Lu, L., Alvarez-Fischer, D., Carrillo-de Sauvage, M. A., Saurini, F., Coussieu, C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017820108 · Cited by 231 · see citing works
“GC-GR responses to neuronal injury are complex, for instance, an excess of GCs (such as occurs in chronic stress) was found to exacerbate neuronal injury in experimental ischemia (9), while an important neuronal survival effect of GR was demonstrated in an acute lipopolysaccharide (LPS)-induced inflammatory lesion mod…”
BackgroundGenomic and epigenomic mechanisms of glucocorticoids in the brain
Gray, J. D., Kogan, J. F., Marrocco, J., & McEwen, B. S. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.97 · Cited by 242 · see citing works
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“Moreover, peripheral and central IL-1 can initiate neuroendocrine responses that promote activation and redistribution of peripheral myeloid cells (Bierhaus et al., 2003; Sternberg, 2006; Sorrells et al., 2009; Dhabhar et al., 2012).”
BackgroundInnate Immunity and Neuroinflammation
Shastri, A., Bonifati, D. M., & Kishore, U. (2013) · Mediators of Inflammation · doi:10.1155/2013/342931 · Cited by 201 · see citing works
“Glucocorticoids have also been considered to play a regulatory role for innate immunity in CNS by regulation of microglial TNF-α [22, 23] although there are debatable views to the same [24].”
BackgroundPerinatal high fat diet alters glucocorticoid signaling and anxiety behavior in adulthood
Sasaki, A., de Vega, W. C., St-Cyr, S., Pan, P., & McGowan, P. O. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.02.044 · Cited by 194 · see citing works
“…molecules I-kappa-B-alpha (IkBa), mitogen-activated protein kinase phosphatase-1 (MKP-1) and interleukin-1 receptor antagonist (IL-1Ra) via changes in GR, NFkB and IL-6 signaling (Sorrells et al., 2009), but their regulation in the context of the inflammatory response to high-fat diet is unknown.”
BackgroundInfluentialDiscrimination and systemic inflammation: A critical review and synthesis
Cuevas, A. G., Ong, A. D., Carvalho, K., Ho, T., Chan, S. W., Allen, J. D., Chen, R., Rodgers, J., Biba, U., & Williams, D. R. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.07.017 · Cited by 189 · see citing works
Regulatory and Mechanistic Actions of Glucocorticoids on T and Inflammatory Cells
Liberman, A. C., Budziñski, M. L., Sokn, C., Gobbini, R. P., Steininger, A., & ARZT, E. S. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00235 · Cited by 185 · see citing works
Won, E., & Kim, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186546 · Cited by 184 · see citing works
“Excess cortisol increases mineralocorticoid receptor affinity, and when bound to the mineralocorticoid receptor, cortisol has proinflammatory effects [21].”
BackgroundDysregulated neuronal–microglial cross-talk during aging, stress and inflammation
Jurgens, H. A., & Johnson, R. W. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2010.11.014 · Cited by 179 · see citing works
“as the timing of stress or stress hormone exposure relative to immune activation (Dhabhar, 2009; Sorrells et al., 2009).”
BackgroundChronic stress as a risk factor for Alzheimer’s disease
Machado, A., Herrera, A. J., de Pablos, R. M., Espinosa‐Oliva, A. M., Soto, M. S., Ayala, A., Venero, J. L., Santiago, M., Villarán, R. F., Delgado‐Cortés, M. J., et al. (2014) · Reviews in the Neurosciences · doi:10.1515/revneuro-2014-0035 · Cited by 177 · see citing works
“Thus, it was hard to discuss that GCs increased inflammation under chronic stress, as has been perfectly shown by Sapolsky’s group (Sorrells et al., 2009).”
BackgroundMunhoz, C. D., Sorrells, S. F., Caso, J. R., Scavone, C., & Sapolsky, R. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0303-09.2010 · Cited by 169 · see citing works
“Nonetheless, an emerging literature shows that, counter to expectations, there are circumstances following an inflammatory challenge or insult where GCs or stress enhance rather than blunt inflammation (for review, see Sorrells et al., 2009).”
BackgroundResultInfluentialSelf-citationNeuroimmune Mechanisms of Alcohol and Drug Addiction
Cui, C., Shurtleff, D., & Harris, R. A. (2014) · International review of neurobiology · doi:10.1016/b978-0-12-801284-0.00001-4 · Cited by 163 · see citing works
Microglia in neuronal plasticity: Influence of stress
Delpech, J.-C., Madore, C., Nadjar, A., Joffre, C., Wohleb, E. S., & Layé, S. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.12.034 · Cited by 157 · see citing works
“glial activation (Silverman and Sternberg, 2012; Sorrells et al., 2009; Sorrells and Sapolsky, 2007).”
Herbert, J., & Lucassen, P. J. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.12.001 · Cited by 150 · see citing works
“Persistent elevations of GCs are pro-rather than anti-inflammatory in the brain (Sorrells et al., 2009).”
BackgroundStress induced microglial activation contributes to depression
Li, B., Yang, W., Ge, T., Wang, Y., & Cui, R. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106145 · Cited by 147 · see citing works
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“This is important because corticosterone generally suppresses inflammatory signaling but also has pleiotropic effects (Sorrells et al., 2009).”
BackgroundLehmann, M. L., Weigel, T. K., Poffenberger, C. N., & Herkenham, M. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.0184-19.2019 · Cited by 138 · see citing works
“More recently, the role of glucocorticoids in influencing CNS neuroinflammation has been explored (Sorrells et al., 2009; Frank et al., 2015), and less emphasis has been placed on oxidative stress.”
BackgroundGanguly, P., & Brenhouse, H. C. (2015) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2014.07.001 · Cited by 136 · see citing works
“Altered trajectories in neuroinflammation and behavior after early life adversity Prabarna Ganguly, Heather C. Brenhouse ∗”
BackgroundThe Gut Microbiome Regulates Psychological-Stress-Induced Inflammation
Xu, C., Lee, S. K., Zhang, D., & Frenette, P. S. (2020) · Immunity · doi:10.1016/j.immuni.2020.06.025 · Cited by 131 · see citing works
“Thus, the effects of glucocorticoids on the immune system are complex as glucocorticoids may promote immune responses in certain circumstances (Sorrells et al., 2009).”
BackgroundChecks and balances: The glucocorticoid receptor and NFĸB in good times and bad
Bekhbat, M., Rowson, S. A., & Neigh, G. N. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.05.001 · Cited by 133 · see citing works
Stress, Definitions, Mechanisms, and Effects Outlined
Fink, G. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800951-2.00001-7 · Cited by 137 · see citing works
Piirainen, S., Youssef, A. M., Song, C., Kalueff, A. V., Landreth, G. E., Malm, T., & Tian, L. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.046 · Cited by 125 · see citing works
“The major mechanism by which stress primes microglia involves the hypothalamic-pituitary-adrenal (HPA) axis, as stress induces systemic glucocorticoid (GC) secretion via the HPA axis, which regulates microglia and their expression of immune genes (Sorrells et al., 2009).”
Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period
Whiteus, C., Freitas, C., & Grutzendler, J. (2013) · Nature · doi:10.1038/nature12821 · Cited by 122 · see citing works
The etiology of poststroke-depression: a hypothesis involving HPA axis
Zhou, L., Wang, T., Yu, Y., Li, M., Sun, X., Song, W., Wang, Y., Zhang, C., & Fu, F. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113146 · Cited by 126 · see citing works
Mediators of allostasis and systemic toxicity in bipolar disorder.
Grande, I., Magalhães, P., Kunz, M., Vieta, E., & Kapczinski, F. (2012) · Physiology and Behavior · doi:10.1016/j.physbeh.2011.10.029 · Cited by 121 · see citing works
“Although renowned for their anti-inflammatory actions, these hormones, under the right conditions, worsen neuroinflammation by rendering neurons less capable to remove glutamate from the synapse and quench free radicals [50].”
Systemic lupus erythematosus, the brain, and anti-NR2 antibodies
Lauvsnes, M. B., & Omdal, R. (2011) · Journal of Neurology · doi:10.1007/s00415-011-6232-5 · Cited by 115 · see citing works
“Increased susceptibility for neuronal loss due to ischemia and excitotoxins [57, 67] 624 J Neurol (2012) 259:622–629”
BackgroundFactors Affecting Blast Traumatic Brain Injury
Kamnaksh, A., Kövesdi, E., Kwon, S.-K. C., Wingo, D., Ahmed, F. A. K. M., Grunberg, N. E., Long, J. B., & Agoston, D. V. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.1983 · Cited by 117 · see citing works
“Abnormal serum CORT levels can alter the inflammatory response (Garcia-Bueno et al., 2008; Miller et al., 2009; Sorrells et al., 2009).”
The Relationship between Stress, Inflammation, and Depression
Kim, I. B., Lee, J.-H., & Park, S. (2022) · Biomedicines · doi:10.3390/biomedicines10081929 · Cited by 126 · see citing works
Chronic Stress and Diabetes Mellitus: Interwoven Pathologies
Sharma, V. K., & Singh, T. G. (2020) · Current Diabetes Reviews · doi:10.2174/1573399815666191111152248 · Cited by 116 · see citing works
Maternal high-fat diet alters anxiety behavior and glucocorticoid signaling in adolescent offspring
Sasaki, A., Vega, W. D., Sivanathan, S., St-Cyr, S., & McGowan, P. O. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.012 · Cited by 116 · see citing works
“In conditions of chronic stress, increased GR expression is required for an enhanced inflammatory response when NFkB expression is elevated (Sorrells et al., 2009).”
InfluentialThe Pro-inflammatory Effects of Glucocorticoids in the Brain
Duque, É. D. A., & Munhoz, C. D. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00078 · Cited by 115 · see citing works
Self-citationNeuroimmune and neuroendocrine abnormalities in depression: two sides of the same coin
Horowitz, M. A., & Zunszain, P. A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12781 · Cited by 110 · see citing works
Audet, M., Jacobson‐Pick, S., Wann, B. P., & Anisman, H. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.03.010 · Cited by 111 · see citing works
“…having immunosuppressive properties, it appears that under certain conditions glucocorticoids may act in a proinflammatory fashion, depending on a constellation of factors, including the timing of corticosterone elevation relative to an immune challenge (Frank et al., 2010; Sorrells et al., 2009).”
BackgroundVezzani, A., Dingledine, R. J., & Rossetti, A. O. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1079130 · Cited by 109 · see citing works
“Different studies, however, reported evidence of glucocorticoid-induced aggravation of brain inflammation [116], and exacerbation of cerebral edema and brain injury following dexamethasone in a model of pilocarpine-induced SE [117].”
Backgroundvan de Garde, M. D. B., Martínez, F. O., Melgert, B. N., Hylkema, M. N., Jonkers, R. E., & Hamann, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302138 · Cited by 108 · see citing works
“Many of these diseases are treated with GCs, but recent studies have shown that GCs can have little effect in controlling inflammation in macrophage-dominated diseases (9, 16).”
BackgroundCalorie Restriction as a New Treatment of Inflammatory Diseases
Kökten, T., Hansmannel, F., Ndiaye, N. C., Heba, A.-C., Quilliot, D., Dreumont, N., Arnone, D., & Peyrin‐Biroulet, L. (2020) · Advances in Nutrition · doi:10.1093/advances/nmaa179 · Cited by 104 · see citing works
“The anti- or pro-inflammatory effects of glucocorticoids are context dependent, with variable responses depending upon concentration, time of exposure, the compound type, and also the nature of the stimulus (43).”
BackgroundMeasurement of Steroid Concentrations in Brain Tissue: Methodological Considerations
Taves, M. D., Ma, C., Heimovics, S. A., Saldanha, C. J., & Soma, K. K. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00039 · Cited by 104 · see citing works
“REVIEW ARTICLE published: 26 September 2011 doi: 10.3389/fendo.2011.00039 Measurement of steroid concentrations in brain tissue: methodological considerations”
BackgroundInfluentialChronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation
Nunez, S. G., Rabelo, S. P., Subotic, N., Caruso, J. W., & Knezevic, N. N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26209994 · Cited by 138 · see citing works
“Additionally, excess cortisol may increase the binding to Mineralocorticoid Receptors that can produce a pro-inflammatory response [23,24].”
Restraint stress increases hemichannel activity in hippocampal glial cells and neurons
Orellana, J. A., Moraga‐Amaro, R., DÃaz-Galarce, R., Rojas, S., Maturana, C. J., Stehberg, J., & Sáez, J. C. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00102 · Cited by 99 · see citing works
“The term stress defines all physiological and/or psychological responses to events that Frontiers in Cellular Neuroscience | www.frontiersin.org 1 April 2015 | Volume 9 | Article 102 require behavioral adjustment to overcome them (Sorrells et al., 2009; Popoli et al., 2011).”
BackgroundRegulatory role of the cannabinoid CB2receptor in stress‐induced neuroinflammation in mice
Zoppi, S., Madrigal, J. L. M., Caso, J. R., García‐Gutiérrez, M. S., Manzanares, J., Leza, J. C., & García‐Bueno, B. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12607 · Cited by 99 · see citing works
“The relationship between stress and the immune system has been extensively studied over the last few decades (Licinio and Wong, 1999; Sorrells et al., 2009), but the precise mechanisms involved are still a matter of debate, probably due to the complex interactions existing between the periphery and the CNS (Capuron an…”
BackgroundSelf-citationMurray, C., Skelly, D., & Cunningham, C. M. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-50 · Cited by 98 · see citing works
“Thus glucocorticoids can exacerbate CNS inflammation rather than suppress it in certain situations (reviewed in [48]).”
BackgroundOrellana, A. M., Vasconcelos, A. R., Leite, J. A., Lima, L. D. S., Andreotti, D. Z., Munhoz, C. D., Kawamoto, E. M., & Scavone, C. (2015) · Aging · doi:10.18632/aging.100853 · Cited by 96 · see citing works
Self-citationSivanathan, S., Thavartnam, K., Arif, S., Elegino, T., & McGowan, P. O. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.02.036 · Cited by 93 · see citing works
“The behavioural impacts of alterations in corticosteroid receptors and associated downstream inflammatory processes in the context of dysregulated corticosterone receptor expression are increasingly recognized but remain poorly understood [18].”
BackgroundInfluentialFrank, M. G., Fonken, L. K., Dolzani, S. D., Annis, J. L., Siebler, P. H., Schmidt, D., Watkins, L. R., Maier, S. F., & Lowry, C. A. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.05.020 · Cited by 91 · see citing works
Glucocorticoids Increase Excitotoxic Injury and Inflammation in the Hippocampus of Adult Male Rats
Sorrells, S. F., Munhoz, C. D., Manley, N. C., Yen, S., & Sapolsky, R. M. (2014) · Neuroendocrinology · doi:10.1159/000367849 · Cited by 90 · see citing works
Self-citationMaternal Obesity as a Risk Factor for Brain Development and Mental Health in the Offspring
Cirulli, F., Musillo, C., & Berry, A. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.01.023 · Cited by 90 · see citing works
“, 2014) investigated the expression of several inflammatory genes linked to GC signaling (Sorrells et al., 2009) as a result of perinatal exposure to HFD (Bilbo and Tsang, 2010).”
BackgroundAcute phase proteins in cattle and swine: A review
Saco, Y., & Bassols, A. (2022) · Veterinary Clinical Pathology · doi:10.1111/vcp.13220 · Cited by 93 · see citing works
Luarte, A., Cisternas, P., Caviedes, A., Bátiz, L. F., Lafourcade, C., Wyneken, Ú., & Henzi, R. (2017) · Stem Cells International · doi:10.1155/2017/1719050 · Cited by 87 · see citing works
Lotrich, F. E., Butters, M. A., Aizenstein, H. J., Marron, M. M., Reynolds, C. F., & Gildengers, A. G. (2013) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4048 · Cited by 83 · see citing works
“Additionally, elevated glucocorticoids may worsen this ongoing neuroinflammatory response by rendering neurons less capable of removing synaptic glutamate and stopping free radical formation—ultimately resulting in premature cell death (Sorrells et al., 2009).”
BackgroundKelly, K. A., Miller, D. B., Bowyer, J. F., & O'Callaghan, J. P. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07864.x · Cited by 82 · see citing works
“The mechanisms through which CORT acts chronically to exert a proinflammatory effect in the intact or injured CNS have been proposed (Sorrells et al. 2009), but largely remain to be identified and characterized (Sorrells and Sapolsky 2007; Sorrells et al. 2009).”
Wesarg, C., van den Akker, A. L., Oei, N. Y. L., Hoeve, M., & Wiers, R. W. H. J. (2020) · European Journal of Developmental Psychology · doi:10.1080/17405629.2020.1748594 · Cited by 81 · see citing works
Epigenetic programming of neurodegenerative diseases by an adverse environment
Babenko, O., Kovalchuk, I., & Metz, G. A. S. (2012) · Brain Research · doi:10.1016/j.brainres.2012.01.038 · Cited by 80 · see citing works
“…compromised chemoresistance to oxidative stress (Landriscina et al., 2009), exaggerated activation of inflammatory cascades (Matsunaga et al., 2011; Sorrells et al., 2009), altered neurotrophic factor expression (Smith et al., 1995) or facilitated cytoplasmic protein accumulation (Sotiropoulos et…”
BackgroundInfluentialTargeting Microglial Activation in Stroke Therapy: Pharmacological Tools and Gender Effects
Chen, Y., Won, S. J., Xu, Y., & Swanson, R. A. (2014) · Current Medicinal Chemistry · doi:10.2174/0929867321666131228203906 · Cited by 74 · see citing works
“It has also been reported that corticosteroids have a direct proapoptotic effect on certain neuronal populations [21], and in some settings they can paradoxically exacerbate inflammation [22, 23].”
BackgroundStress-Induced Cytokines and Neuronal Dysfunction in Alzheimer's Disease
Ricci, S., Fuso, A., Ippoliti, F., & Businaro, R. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110821 · Cited by 76 · see citing works
“In particular several studies demonstrated that GC binding to GR makes neurons, especially those localized within the hippocampus, less capable to survive a variety of insults [40].”
Stress disinhibits microglia via down-regulation of CD200R: A mechanism of neuroinflammatory priming
Frank, M. G., Fonken, L. K., Annis, J. L., Watkins, L. R., & Maier, S. F. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.11.001 · Cited by 77 · see citing works
The Impact of Obesity on Microglial Function: Immune, Metabolic and Endocrine Perspectives
Alexaki, V. I. (2021) · Cells · doi:10.3390/cells10071584 · Cited by 83 · see citing works
Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects
Walter, T. J., Vetreno, R. P., & Crews, F. T. (2017) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13511 · Cited by 75 · see citing works
“…Alcohol Clin Exp Res, Vol 41, No 12, 2017: pp 2066–2081 ALCOHOLISM: CLINICAL AND EXPERIMENTAL RESEARCH Vol. 41, No. 12 December 2017 hypothesized to have the opposite effect of enhancing brain innate immune signaling under some circumstances (Frank et al., 2015; Sorrells et al., 2009).”
BackgroundInfluentialKuang, N., Liu, Z., Yu, G., Wu, X., Becker, B., Fan, H., Peng, S., Zhang, K., Zhao, J., Kang, J., et al. (2023) · BMC Medicine · doi:10.1186/s12916-023-02920-9 · Cited by 79 · see citing works
“…that results in a poorly defined gray–white boundary [43] and therefore thicker gray matter [44] during development, while astrocyte/microglia over activation [51] accompanied by more pro-inflammatory cytokines in children [80, 81] may lead to a reduction in neuronal/synaptic density [79].”
BackgroundMatisz, C. E., & Gruber, A. J. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.12.020 · Cited by 70 · see citing works
Stress and social isolation increase vulnerability to stroke
Stuller, K. A., Jarrett, B. L., & DeVries, A. C. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.01.016 · Cited by 74 · see citing works
Social neuroscience: The social brain, oxytocin, and health
Norman, G. J., Hawkley, L. C., Cole, S. W., Berntson, G. G., & Cacioppo, J. T. (2011) · Social Neuroscience · doi:10.1080/17470919.2011.568702 · Cited by 72 · see citing works
“Given the broad influence of glucocorticoids on immune function (McEwen & Gianaros, 2010 ; Sorrells, Caso, Munhoz, & Sapolsky, 2009 ), the dysregulation of cortisol signaling may also mediate the relationship between perceived social isolation, immune function, and health.”
BackgroundBuga, A.-M., Napoli, M. D., & Popa‐Wagner, A. (2013) · Biogerontology · doi:10.1007/s10522-013-9465-0 · Cited by 71 · see citing works
“The response of the normal adult brain to ischemiainduced neuroinflammation greatly depends upon the type and duration of the ischemia (Pal et al. 2012).”
BackgroundGreater glucocorticoid receptor activation in hippocampus of aged rats sensitizes microglia
Barrientos, R. M., Thompson, V. M., Kitt, M. M., Amat, J., Hale, M. W., Frank, M. G., Crysdale, N. Y., Stamper, C. E., Hennessey, P. A., Watkins, L. R., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.12.003 · Cited by 70 · see citing works
“However, a more complex view that CORT actually has pleiotropic actions has emerged over the last dozen years (Busillo et al., 2011; Sorrells and Sapolsky, 2007; Sorrells et al., 2009).”
BackgroundLea, A. J., Akinyi, M. Y., Nyakundi, R. K., Mareri, P., Nyundo, F., Kariuki, T., Alberts, S. C., Archie, E. A., & Tung, J. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811967115 · Cited by 66 · see citing works
“Given that glucocorticoids, and perhaps testosterone, can suppress some immune responses [although glucocorticoids can promote inflammation in some cases (53, 54)], males that can maintain active innate immune defense systems in the face of these hormone signals may be of particularly high quality (55, 56).”
BackgroundMicroglia and HPA axis in depression: An overview of participation and relationship
Pereira, G. C., Piton, E., dos Santos, B. M., Ramanzini, L. G., Camargo, L. F. M., da Silva, R. M., & Bochi, G. V. (2021) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2021.1939154 · Cited by 69 · see citing works
“Studies suggest the GCs as mediators of stress-related inflammation by modulating microglia in the CNS (Sorrells et al. 2009; Munhoz et al. 2010).”
BackgroundThe hormesis principle of neuroplasticity and neuroprotection
Mattson, M. P., & Leak, R. K. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.022 · Cited by 75 · see citing works
UFRGS-UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL
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Neuroinflammation, Early-Life Adversity, and Brain Development
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Exercise is not beneficial and may accelerate symptom onset in a mouse model of Huntington’s disease
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“Applying physical exercise to a mouse genetically predisposed to develop HD may have caused unwelcome stress to an already vulnerable system [38] .”
BackgroundNeurotrophins, inflammation and oxidative stress as illness activity biomarkers in bipolar disorder
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“hours) may be very different from that of chronic stress [6].”
BackgroundChronic glucocorticoid exposure activates BK-NLRP1 signal involving in hippocampal neuron damage
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Bidirectional relations between depression symptoms and chronic kidney disease
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“74 With some neurological insults, such as trauma, stroke, and seizure, glucocorticoids can increase cytokine activation, thereby exacerbating neurotoxicity and contributing to neuronal loss, particularly of hippocampal neurons.”
Neuroendocrine and Immune Influences on the CNS: It's a Matter of Sex
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“Inflammation is known to be a biological consequence of stress and HPA axis alterations [18].”
BackgroundGlucocorticoid sensitization of microglia in a genetic mouse model of obesity and diabetes
Dey, A., Hao, S., Erion, J., Wosiski‐Kuhn, M., & Stranahan, A. M. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.01.013 · Cited by 60 · see citing works
“In the context of protracted exposure, such as that which occurs in chronic stress, anti-inflammatory effects are reversed, and glucocorticoids convert from anti-inflammatory to pro-inflammatory (Sorrells et al., 2009).”
Background
- Authors
- Sorrells, S. F., Caso, J. R., Munhoz, C. D., & Sapolsky, R. M.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Universidade de São Paulo (BR)
- Corresponding author
- Sorrells, Shawn F.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 64
- Issue
- 1
- Pages
- 33-39
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4782919
- OpenAlex
- W2062298786
- Cited by
- 425
- References
- 52
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 26 · 2023: 22 · 2022: 30 · 2021: 31 · 2020: 28 · 2019: 20 · 2018: 34 · 2017: 29 · 2016: 19 · 2015: 27 · 2014: 35 · 2013: 22 · 2012: 28
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS059918, F31NS063491)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- glucocorticoids, neuroinflammation, stress response, neuroendocrine-immune interaction
- MeSH terms
- Animals, Brain, Encephalitis, Glucocorticoids, Humans, Inflammation, Models, Neurological, Myelitis, Neurons, Spinal Cord, Stress, Physiological, Neuroimmunomodulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.
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