The Stressed CNS: When Glucocorticoids Aggravate Inflammation

In the paper

“indeed subacute stress induces GR-dependent microglia proliferation (Nair and Bonneau, 2006)”

What the sources say

• Not checked yetcites Nair and Bonneau, 2006

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).”

What the sources say

• Not checked yetcites Johnson et al., 2002 source

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.”

What the sources say

• Not checked yetcites Sapolsky, 1999 source

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).”

What the sources say

• Not checked yetcites De Bosscher et al., 2003 source

In the paper

“In the absence of injury, acute stress can activate inflammatory mediators in the CNS.”

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.”

In the paper

“indeed, impaired CORT secretion is implicated in several autoimmune disorders (Wick et al., 1993).”

What the sources say

• Not checked yetcites Wick et al., 1993

In the paper

“By contrast, acute stress post-LPS decreases the production of these same cytokines (Goujon et al., 1995).”

What the sources say

• Not checked yetcites Goujon et al., 1995 source

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).”

What the sources say

• Not checked yetcites Frank et al., 2009

In the paper

“Reciprocally, MAPK (ERK and JNK) can decrease GR nuclear transport and affinity to cofactors via phosphorylation (Rogatsky et al., 1998).”

What the sources say

• Not checked yetcites Rogatsky et al., 1998 source

In the paper

“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).”

What the sources say

• Not checked yetcites Zhao et al., 2005 source

In the paper

“At least some of these stress effects are GC dependent and GR mediated (Garcia-Bueno et al., 2008).”

What the sources say

• Not checked yetcites Garcia-Bueno et al., 2008 source

In the paper

“The former conclusion is likely because GCs can augment LPS-induced CNS inflammation in the absence of neuronal death.”

In the paper

“Numerous studies demonstrate that GC signaling via GR makes neurons (most notably in the hippocampus) less capable of surviving a variety of insults.”

In the paper

“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).”

What the sources say

• Not checked yetcites McEwen et al., 1997 source

In the paper

“As evidence, prior acute stress worsens stroke damage by increasing IL-1β levels in the postischemic cortex (Caso et al., 2007).”

What the sources say

• Not checked yetcites Caso et al., 2007 source

In the paper

“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).”

What the sources say

• Not checked yetcites Barber et al., 1993 source

In the paper

“Importantly, in this study, chronic stress occurred after the injury, but still increased LPS-induced TNF-α expression and microglia activation.”

What the sources say

• Not checked yetcites de Pablos et al., 2006 source

In the paper

“Whether GCs increase or decrease CNS inflammation depends on the dose, timing, duration of GC exposure, and the type of GC”

In the paper

“By contrast, CORT diminishes the expression of these same cytokines when given 1 hr post LPS.”

What the sources say

• Not checked yetcites Frank et al., 2009

In the paper

“Moreover, chronic exposure to GCs (particularly synthetic GCs at supra-physiological levels) inhibits both innate and adaptive immunity.”

What the sources say

• Not checked yetcites De Bosscher et al., 2003 source

In the paper

“and prior CORT exposure primes cytokine release from microglia ex vivo (Frank et al., 2006).”

What the sources say

• Not checked yetcites Frank et al., 2006 source

In the paper

“Supporting this conclusion, adrenoceptor antagonists inhibit stress-induced increases in CNS cytokine production (Johnson et al., 2005).”

What the sources say

• Not checked yetcites Johnson et al., 2005 source

In the paper

“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.”

In the paper

“Subacute CORT treatment increases inflammatory cell recruitment and cytokine production at an excitotoxic injury site (Dinkel et al., 2003).”

What the sources say

• Not checked yetcites Dinkel et al., 2003 source

In the paper

“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).”

What the sources say

• Not checked yetcites de Pablos et al., 2006 source

In the paper

“Moreover, animals with higher basal CORT levels have a greater accumulation of proinflammatory mediators (Perez-Nievas et al., 2007).”

What the sources say

• Not checked yetcites Perez-Nievas et al., 2007 source

In the paper

“This was seen in one study where GCs increased inflammatory cell infiltration prior to the emergence of neuronal death (Dinkel et al., 2003).”

What the sources say

• Not checked yetcites Dinkel et al., 2003 source

In the paper

“CORT given prior to LPS challenge increases IL-1β and TNF-α expression in the hippocampus (Frank et al., 2009).”

What the sources say

• Not checked yetcites Frank et al., 2009

In the paper

“these GC actions can exacerbate injury-induced neuronal death.”

In the paper

“If stress occurs prior to immune activation, it can have a “priming” effect that makes the subsequent response greater.”

In the paper

“Acute GC exposure induces sustained expression of MKP-1 in a variety of cells including macrophages (Roger et al., 2005).”

What the sources say

• Not checked yetcites Roger et al., 2005 source

In the paper

“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).”

What the sources say

• Not checked yetcites de Pablos et al., 2006 source

In the paper

“In addition to GR phosphorylation, the balance between NF-κB and GR signaling is important in predicting GC actions.”

In the paper

“As discussed, GR activation is required for chronic-stress-augmented NF-κB activation”

In the paper

“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).”

What the sources say

• Not checked yetcites Bladh et al., 2005 source