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Review
. 2014 Oct;5(5):543-53.
doi: 10.1007/s12975-014-0349-7. Epub 2014 Jun 5.

Molecular and cellular immune responses to ischemic brain injury

Hilary A Seifert  1 , Keith R Pennypacker
Affiliations
Review

Molecular and cellular immune responses to ischemic brain injury

Hilary A Seifert et al. Transl Stroke Res. 2014 Oct.

Abstract

Despite extensive research into stroke pathology, there have not been any major recent advancements in stroke therapeutics. Animal models of cerebral ischemia and clinical data have been used to investigate the progressive neural injury that occurs after an initial ischemic insult. This has lead researchers to focus more on the peripheral immune response that is generated as a result of cerebral ischemia. The therapies that have been developed as a result of this research thus far have proven ineffective in clinical trials. The failure of these therapeutics in clinical trials is thought to be due to the broad immunosuppression elicited as a result of the treatments and the cerebral ischemia itself. Emerging evidence indicates a more selective modulation of the immune system following stroke could be beneficial. The spleen has been shown to exacerbate neural injury following experimental stroke and would provide a strong therapeutic target. Selecting facets of the immune system to target would allow the protective and regenerative properties of the immune response to remain intact while blunting the pro-inflammatory response generated towards the injured brain.

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Figures

Fig. 1
Fig. 1
The generation of an interferon gamma driven immune response following stroke After a stroke there is an increase in systemic circulating catecholamines that causes a decrease in spleen size. At the same time there is an increase in splenic interferon gamma (IFNγ). There is then a delayed increase in the expression of IFNγ in the brain, which activates microglia and macrophages. Activation of these cells causes increased expression of interferon-inducible protein 10 (IP-10) and increased neural injury. The elevated levels of IP-10 create a pro-inflammatory loop by recruiting more IFNγ producing cells to the brain (a). Blocking or interfering with IFNγ signaling is a potential therapeutic option as blocking IFNγ would decrease microglia/macrophage activation, IP-10 expression, and prevent further increases in IFNγ in the brain resulting in decreased neural injury following stroke (b).
See this image and copyright information in PMC

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