Modulation of Neuro-Inflammation and Vascular Response by Oxidative Stress Following Cerebral Ischemia-Reperfusion Injury

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Abstract:

The mechanisms leading to cellular damage from ischemia-reperfusion (I/R) injury are complex and multi-factorial. Accumulating evidence suggests an important role for oxidative stress in the regulation of neuro-inflammation following stroke. Gene expression studies have revealed that the increase in oxygen radicals post-ischemia triggers the expression of a number of pro-inflammatory genes. These genes are regulated by the transcription factor, nuclear factor-kappa-B (NF-??B) which is redox-sensitive. It is hypothesised that changes in the oxidative state may modulate alterations in the neuro-inflammatory response following an I/R injury. Furthermore, NF-??B is involved in the transcriptional regulation of adhesion molecules, which play an important role in leukocyte-endothelium interactions. Recent studies have demonstrated that adhesion molecule-mediated leukocyte recruitment is associated with increased tissue damage in stroke, while mice lacking key adhesion molecules conferred neuro-protection. Nevertheless, the involvement of oxidative stress in leukocyte recruitment and the subsequent regulated cell injury is yet to be elucidated. While leukocyte infiltration into the ischemic brain is detrimental, leukocyte accumulation in the microvasculature was shown to be one of the many factors implicated in reduced reperfusion. Although this “no-reflow” phenomenon was confirmed in a variety of animal models of cerebral ischemia, the exact mechanism is still uncertain. This review aims to highlight the impact that oxidative stress has in the regulation of post-ischemic neuro-inflammation and the implication for the cerebral microvasculature after injury.

Keywords: Glutathione Peroxidase; Ischemic strokes; NADPH; Reactive Oxygen Species; Superoxide Dismutase; cerebral ischemia

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986708783330665

Affiliations: Department of Pharmacology, The University of Melbourne, Parkville, Victoria, 3010, Australia.

Publication date: January 1, 2008

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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