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Review
. 2014;21(18):2076-97.
doi: 10.2174/0929867321666131228205146.

Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets

J Y Kim, M Kawabori, M A Yenari  1
Affiliations
Review

Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets

J Y Kim et al. Curr Med Chem. 2014.

Abstract

Stroke is a frequent cause of long-term disability and death worldwide. Ischemic stroke is more commonly encountered compared to hemorrhagic stroke, and leads to tissue death by ischemia due to occlusion of a cerebral artery. Inflammation is known to result as a result of ischemic injury, long thought to be involved in initiating the recovery and repair process. However, work over the past few decades indicates that aspects of this inflammatory response may in fact be detrimental to stroke outcome. Acutely, inflammation appears to have a detrimental effect, and anti-inflammatory treatments have been been studied as a potential therapeutic target. Chronically, reports suggest that post-ischemic inflammation is also essential for the tissue repairing and remodeling. The majority of the work in this area has centered around innate immune mechanisms, which will be the focus of this review. This review describes the different key players in neuroinflammation and their possible detrimental and protective effects in stroke. A better understanding of the roles of the different immune cells and their temporal profile of damage versus repair will help to clarify more effective modulation of inflammation post stroke.

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Figures

Figure 1
Figure 1
The structure of the active NADPH oxidase complex in stroke. The NADPH oxidase comprises a cytosolic subunits (p47phox, p67phox, p40phox and Rac) and membrane subunits (gp91phox and p22phox) which associate with this complex in the activated enzyme. The NADPH-binding domain is predicted to be on one side of the membrane, whereas O2•–generation is predicted to occur on the other in stroke.
Figure 2
Figure 2
Several transcription factors have been documented in the inflammatory response, Ischemic injury activates IKK and MAPK cascade to stimulate IkB, SAPK/JNK, p38 MAPKs and ERK phosphorylation, leading to transcription factors; NF-kB (subunit p50 and p65) and AP-1 (phosphorylation of c-Jun and upregulation of c-Fos) activation and then enhances pro-inflammatory genes expression.
See this image and copyright information in PMC

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