The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index; none of the 41 sources its claims cite is checked for support yet.
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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39 Not checked yet · 8 Own interpretation · 3 No basis given
In the paper
“indeed subacute stress induces GR-dependent microglia proliferation (Nair and Bonneau, 2006)”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Putative Mechanisms underlying the Inflammation-Enhancing Effects of GCs
What the sources say
- Not checked yetcites Nair and Bonneau, 2006
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Acute CORT Exposure Primes a Subsequent Inflammatory Response
What the sources say
- Not checked yetcites Johnson et al., 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“One mechanism to explain these endangering effects of CORT is that the hormone decreases glucose transport into neurons and glia in the hippocampus.”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Functional Implications: GCs Endanger Injured Neurons
What the sources say
- Not checked yetcites Sapolsky, 1999 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“GCs also decrease immune activation via protein-protein interactions between GR and NF-κB in the nucleus (Figure 1) (De Bosscher et al., 2003).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > When GCs Are Immunosuppressive
What the sources say
- Not checked yetcites De Bosscher et al., 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“In the absence of injury, acute stress can activate inflammatory mediators in the CNS.”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Stress and the Uninjured CNS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Functional Implications: GCs Endanger Injured Neurons
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Functional Implications: GCs Endanger Injured Neurons · hedged
In the paper
“indeed, impaired CORT secretion is implicated in several autoimmune disorders (Wick et al., 1993).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > When GCs Are Immunosuppressive
What the sources say
- Not checked yetcites Wick et al., 1993
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“By contrast, acute stress post-LPS decreases the production of these same cytokines (Goujon et al., 1995).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Acute CORT Exposure Primes a Subsequent Inflammatory Response
What the sources say
- Not checked yetcites Goujon et al., 1995 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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In the paper
“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).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Acute CORT Exposure Has Priming Effects on Inflammation in the CNS
What the sources say
- Not checked yetcites Frank et al., 2009
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Reciprocally, MAPK (ERK and JNK) can decrease GR nuclear transport and affinity to cofactors via phosphorylation (Rogatsky et al., 1998).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Putative Mechanisms underlying the Inflammation-Enhancing Effects of GCs
What the sources say
- Not checked yetcites Rogatsky et al., 1998 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- It may state two separate claims as one. 13
- Probably not a substantial claim. 1
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both GCs and stress (in a GC-and GR-dependent manner) can augment aspects of inflammation in the CNS”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Abstract
plainconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Conclusions · plain
In the paper
“Basal CORT levels induce SHIP1, which increases NF-κB activation by inhibiting AKT (Zhang and Daynes, 2007).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Putative Mechanisms underlying the Inflammation-Enhancing Effects of GCs
What the sources say
- Not checked yetcites Zhang and Daynes, 2007
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This led to the theory that CORT secretion during stress actually mediates recovery from this initial immune activation (Munck et al., 1984).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > When GCs Are Immunosuppressive
What the sources say
- Not checked yetcites Munck et al., 1984 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Functional Implications: GCs Endanger Injured Neurons
What the sources say
- Not checked yetcites Sapolsky and Pulsinelli, 1985
- Not checked yetcites Dinkel et al., 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, subacute stress induces an increase in TNF-α levels in the cortex, and blocking this increase lessens stroke damage (Caso et al., 2006).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Functional Implications: GCs Endanger Injured Neurons
What the sources say
- Not checked yetcites Caso et al., 2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Higher levels of CORT antagonize MAPK signaling by inducing expression of MAPK phosphatase-1 (MKP-1), which reduces NF-κB activation.”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Putative Mechanisms underlying the Inflammation-Enhancing Effects of GCs
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Stress and the Uninjured CNS
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > When GCs Are Immunosuppressive
What the sources say
- Not checked yetcites De Bosscher et al., 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Acute CORT Exposure Primes a Subsequent Inflammatory Response
What the sources say
- Not checked yetcites Smyth et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Brain Regional Differences in GC Effects
What the sources say
- Not checked yetcites Munhoz et al., 2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Basal GC Concentrations Are Required for Immune Activation
What the sources say
- Not checked yetcites Wurtman and Axelrod, 1966
- Not checked yetcites Joels and de Kloet, 1989 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Conclusions
What the sources say
- Not checked yetcites Gomes et al., 2005 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ The Stressed CNS: When Glucocorticoids Aggravate Inflammation > Putative Mechanisms underlying the Inflammation-Enhancing Effects of GCs
What the sources say
- Not checked yetcites Galon et al., 2002 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
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“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]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measured
Citations
Cites
(2005) · Choice Reviews Online · doi:10.5860/choice.43-0626 · Cited by 4,726
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396
Physiological functions of glucocorticoids in stress and their relation to pharmacological actions
MUNCK, A., GUYRE, P. M., & HOLBROOK, N. J. (1984) · Endocrine Reviews · doi:10.1210/edrv-5-1-25 · Cited by 3,083
Brain corticosteroid receptor balance in health and disease
de Kloet, E. R., Vreugdenhil, E., Oitzl, M. S., & Joëls, M. (1998) · Endocrine Reviews · doi:10.1210/edrv.19.3.0331 · Cited by 2,614
The IκB-NF-κB Signaling Module: Temporal Control and Selective Gene Activation
Hoffmann, A., Levchenko, A., Scott, M. L., & Baltimore, D. (2002) · Science · doi:10.1126/science.1071914 · Cited by 1,890
Dhabhar, F. S., & McEwen, B. S. (1997) · Brain Behavior and Immunity · doi:10.1006/brbi.1997.0508 · Cited by 1,014
De Bosscher, K., Vanden Berghe, W., & Haegeman, G. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0006 · Cited by 898
McEwen, B. S., Biron, C. A., Brunson, K. W., Bulloch, K., Chambers, W. H., Dhabhar, F. S., Goldfarb, R. H., Kitson, R. P., Miller, A. H., Spencer, R. L., et al. (1997) · Brain Research Reviews · doi:10.1016/s0165-0173(96)00012-4 · Cited by 837
Karst, H., Berger, S., Turiault, M., Tronche, F., Schütz, G., & Joëls, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507572102 · Cited by 774
Glucocorticoids Potentiate Ischemic Injury to Neurons: Therapeutic Implications
Sapolsky, R. M., & Pulsinelli, W. A. (1985) · Science · doi:10.1126/science.4035356 · Cited by 678
Self-citation
Cited by
Sorted by citations
Coutinho, A. E., & Chapman, K. E. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.04.005 · Cited by 1,815
“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
“…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
“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
“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
Neuropathogenesis of Delirium: Review of Current Etiologic Theories and Common Pathways
Maldonado, J. R. (2013) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2013.09.005 · Cited by 745
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
“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].”
BackgroundHannibal, K. E., & Bishop, M. D. (2014) · Physical Therapy · doi:10.2522/ptj.20130597 · Cited by 729
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
Kim, Y.-K., Na, K.-S., Myint, A.-M., & Leonard, B. E. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.06.008 · Cited by 620
Slavich, G. M. (2020) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032816-045159 · Cited by 502
“…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
Stress and the brain: Individual variability and the inverted-U
Sapolsky, R. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4109 · Cited by 413
Self-citationBorsook, D., Maleki, N., Becerra, L. R., & McEwen, B. S. (2012) · Neuron · doi:10.1016/j.neuron.2012.01.001 · Cited by 370
“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
Busillo, J. M., & Cidlowski, J. A. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.11.005 · Cited by 339
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
“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 276
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
Sierra, A., Beccari, S., Díaz‐Aparicio, I., Encinas, J. M., Comeau, S., & Tremblay, M. (2014) · Neural Plasticity · doi:10.1155/2014/610343 · Cited by 268
“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 258
“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 248
“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
“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
Wohleb, E. S., Patterson, J. M., Sharma, V., Quan, N., Godbout, J. P., & Sheridan, J. F. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3723-13.2014 · Cited by 209
“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 207
“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
“…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., Ong, A., Carvalho, K., Ho, T., Chan, S.-W., Allen, J., Chen, R., Rodgers, J., Biba, U., & Williams, D. R. (2020) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2020.07.017 · Cited by 166
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 190
Won, E., & Kim, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186546 · Cited by 192
“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
“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 187
“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
“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 172
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 161
“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
“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 151
Niraula, A., Wang, Y., Godbout, J. P., & Sheridan, J. F. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.2568-17.2018 · Cited by 137
“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
“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
“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 137
“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 142
Stress, Definitions, Mechanisms, and Effects Outlined
Fink, G. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800951-2.00001-7 · Cited by 166
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 130
“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 130
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 128
Mediators of allostasis and systemic toxicity in bipolar disorder
Grande, I., Magalhães, P. V. D. S., Kunz, M., Vieta, E., & Kapczinski, F. P. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.10.029 · Cited by 119
“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
“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
“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 133
Chronic Stress and Diabetes Mellitus: Interwoven Pathologies
Sharma, V. K., & Singh, T. G. (2020) · Current Diabetes Reviews · doi:10.2174/1573399815666191111152248 · Cited by 116
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
“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 118
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 119
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 119
“…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 110
“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 112
“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 109
“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
“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
“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 104
“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
“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 100
“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 99
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
“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 101
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
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 97
“, 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
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 91
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 85
“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 83
“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 102
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
“…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 81
“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
“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
The Impact of Obesity on Microglial Function: Immune, Metabolic and Endocrine Perspectives
Alexaki, V. I. (2021) · Cells · doi:10.3390/cells10071584 · Cited by 84
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 71
“…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 80
“…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 71
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
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 77
“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 73
“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
“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 68
“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 72
“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 77
UFRGS-UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL
Saúde, B. D., & Pós-Graduação, P. R. D. (2009) · Cited by 68
Neuroinflammation, Early-Life Adversity, and Brain Development
Andersen, S. L. (2022) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000325 · Cited by 73
Exercise is not beneficial and may accelerate symptom onset in a mouse model of Huntington’s disease
Potter, M. C., Yuan, C., Ottenritter, C., Mughal, M. R., & van Praag, H. (2010) · PLoS Currents · doi:10.1371/currents.rrn1201 · Cited by 68
“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
Pfaffenseller, B., Fries, G. R., Wollenhaupt-Aguiar, B., Colpo, G. D., Stertz, L., Panizzutti, B., Magalhães, P. V., & Kapczinski, F. (2013) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2013.811981 · Cited by 68
Prowse, N. A., & Hayley, S. P. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.09.018 · Cited by 72
Komatsuzaki, Y., Hatanaka, Y., Murakami, G., Mukai, H., Hojo, Y., Saito, M., Kimoto, T., & Kawato, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034124 · Cited by 67
“hours) may be very different from that of chronic stress [6].”
BackgroundChronic glucocorticoid exposure activates BK-NLRP1 signal involving in hippocampal neuron damage
Zhang, B., Zhang, Y., Wu, W., Xu, T., Yin, Y., Zhang, J., Huang, D., & Li, W. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0911-9 · Cited by 66
Bidirectional relations between depression symptoms and chronic kidney disease
Liu, M., Zhang, Y., Yang, S., Wu, Q., Ye, Z., Zhou, C., He, P., Zhang, Y., Hou, F. F., & Qin, X. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.05.104 · Cited by 65
Santarsieri, M., Niyonkuru, C., McCullough, E. H., Dobos, J. A., Dixon, C., Berga, S. L., & Wagner, A. K. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.3177 · Cited by 60
“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
Bale, T. L. (2009) · Neuron · doi:10.1016/j.neuron.2009.09.036 · Cited by 62
Doolin, K., Farrell, C. M., Tozzi, L., Harkin, A., Frodl, T., & O’Keane, V. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102226 · Cited by 64
“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
“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
Metadata
- 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.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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