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Cited by 179Neuroinflammation and Neurodegeneration MechanismsStress Responses and CortisolTraumatic Brain Injury and Neurovascular Disturbances

Novel glucocorticoid effects on acute inflammation in the CNS

Dinkel, Klaus, MacPherson, Anna, Sapolsky, Robert M.·2003·Journal of Neurochemistry
DOI 10.1046/j.1471-4159.2003.01604.x
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Abstract

The CNS can mount an inflammatory reaction to excitotoxic insults that contributes to the emerging brain damage. Therefore, anti-inflammatory drugs should be beneficial in neurological insults. In contrast, glucocorticoids (GCs), while known for their anti-inflammatory effects, can exacerbate neurotoxicity in the hippocampus after excitotoxic insults. We investigated the effect of GCs on the inflammatory response after a neurological insult. Intact control (INT; intact stress response GC profile), adrenalectomized/GC-supplemented (ADX; low basal GC profile) and GC-treated (COR; chronically high GC profile) rats were injected with kainic acid into the hippocampal CA3 region. Lesion size was determined 8-72 h later. The inflammatory response was characterized using immunohistochemistry, RNAse protection assay and ELISA. The INT and COR rats developed larger CA3 lesions than ADX rats. We found that GCs surprisingly caused an increase in relative numbers of inflammatory cells (granulocytes, monocytes/macrophages and microglia). Additionally, mRNA and protein (IL-1beta and TNF-alpha) levels of the pro-inflammatory cytokines IL-1alpha, IL-1beta and TNF-alpha were elevated in COR rats compared with INT and ADX rats. These data strongly question the traditional view of GCs being uniformly anti-inflammatory and could further explain how GCs worsen the outcome of neurological insults.

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Crossref · 10.1046/j.1471-4159.2003.01604.x

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  • There are exceptions to glucocorticoid inhibition of pro-inflammatory cytokines: pro-inflammatory effects of glucocorticoids that depend on dose and cell or tissue type.

    “Yet, there are exceptions – pro-inflammatory effects of glucocorticoids that depend on dose and cell or tissue type (Dinkel et al., 2003; MacPherson et al., 2005).”

    From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Dinkel et al., 2003

  • Proinflammatory effects of glucocorticoids depend on dose and cell or tissue type.

    “Yet, there are exceptions - proinflammatory effects of glucocorticoids that depend on dose and cell or tissue type.6,7”

    From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [6]

  • 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).”

    From The Stressed CNS: When Glucocorticoids Aggravate Inflammation (2009) · cites this paper as Dinkel et al., 2003

  • 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).”

    From The Stressed CNS: When Glucocorticoids Aggravate Inflammation (2009) · cites this paper as Dinkel et al., 2003

  • Subacute 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).”

    From The Stressed CNS: When Glucocorticoids Aggravate Inflammation (2009) · cites this paper as Dinkel et al., 2003

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Authors
Dinkel, K., MacPherson, A., & Sapolsky, R. M.
Affiliations
Stanford University (US)
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2003-01-31
Volume
84
Issue
4
Pages
705-716
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1046/j.1471-4159.2003.01604.x
OpenAlex
W1538656778
Cited by
179
References
52
Citations by year
2025: 2 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 9 · 2020: 9 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 8 · 2015: 7 · 2014: 12 · 2013: 9 · 2012: 7
FWCI
6.35
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (2r01mh053814-04)
  • National Institute of Mental Health (R01 MH 53814)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
glucocorticoids, acute inflammation, central nervous system, excitotoxicity, kainic acid, hippocampus, neuroinflammation, adrenalectomy, stress response, inflammatory cytokines, IL-1β, TNF-α, microglia, macrophages, granulocytes, neurotoxicity
MeSH terms
Acute Disease, Adrenalectomy, Animals, Cell Count, Encephalomyelitis, Glucocorticoids, Granulocytes, Hippocampus, Interleukin-1, Kainic Acid, Macrophages, Male, RNA, Messenger, Steroids, Tumor Necrosis Factor-alpha, Cytokines, Rats, Sprague-Dawley, Microglia, Excitatory Amino Acid Agonists, Rats

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