Expression of COX-1, COX-2, iNOS and p38 in Human Brain with Stroke Lesions
Titel:
Expression of COX-1, COX-2, iNOS and p38 in Human Brain with Stroke Lesions
Auteur:
Zaher A. Radi Nasir K. Khan
Verschenen in:
International journal of pharmacology
Paginering:
Jaargang 4 (2008) nr. 2 pagina's 108-113
Jaar:
2008
Inhoud:
The expression profile of COX-1, COX-2, iNOS and p38, in both the normal and post-ischemic human brain was studied. Focal cerebral ischemia is associated with a marked inflammatory reaction that contributes to the evolution and progression of brain tissue injury. Studies employing anti-inflammatory compounds and transgenic mouse models have suggested that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mediate the deleterious effects of ischemic brain injury. A potential role for the mitogen-activated protein kinase (MAPK) p38 in cytokine production following stroke has been hypothesized. In order to evaluate the expression profiles of COX-1, COX-2, iNOS and p38 in normal and post-ischemic human brain, we evaluated the brain tissue from 12 patients with a pathological diagnosis of cerebrovascular disease (CVD) or cerebrovascular accident (CVA) for expression of COX-1, COX-2, p38 and iNOS via immunohistochemistry (IHC) and in situ hybridization (ISH). Corresponding brain sections from six normal patients served as controls. COX-1, COX-2 and iNOS were all present in the normal brain. However, in infarcted brains, an increase in iNOS and COX-2 expression was observed, with no concomitant change in COX-1 staining or p38 noted. Our data demonstrate up-regulation of both iNOS and COX-2, but not p38 or COX-1, in infarcted brains, bolstering the hypothesis that iNOS, COX-2 and their reaction products contribute to the progression of post-ischemic cerebral injury via cytotoxic, rather than cerebrovascular mechanisms.
Uitgever:
Asian Network for Scientific Information, Pakistan (provided by DOAJ)