Amelioration of hippocampal neuronal damage after transient forebrain ischemia in cyclooxygenase-2-deficient mice.

Abstract

Several studies have suggested that cyclooxygenase-2 (COX-2) plays a role in ischemic neuronal death. Genetic disruption of COX-2 has been shown to reduce susceptibility to focal ischemic injury and N-methyl-d-aspartate-mediated neurotoxicity. The purpose of this study was to examine the effects of COX-2 deficiency on neuronal vulnerability after transient forebrain ischemia. Marked upregulation of COX-2 immunostaining in neurons was observed at the early stage and prominent COX-2 staining persisted in the CA1 medial sector and CA2 sector over 3 days after ischemia. The immunohistologic pattern of COX-2 staining in these sectors gradually condensed to a perinuclear location. The degree of hippocampal neuronal injury produced by global ischemia in COX-2-deficient mice was less than that in wild-type mice, coincident with attenuation of DNA fragmentation in the hippocampus. Also, treatment with a selective COX-2 inhibitor, nimesulide, after ischemia decreased hippocampal neuronal damages. These results of genetic disruption and chemical inhibition of cyclooxygenase-2 show that inhibition of COX-2 ameliorates selective neuronal death after transient forebrain ischemia in mice.

• Authors: Tsutomu Sasaki, Kazuo Kitagawa, Kanato Yamagata, Takako Takemiya, Shigeru Tanaka, Emi Omura-Matsuoka, Shiro Sugiura, Masayasu Matsumoto, Masatsugu Hori
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 24 Issue 1 Pg. 107-13 (Jan 2004) ISSN: 0271-678X [Print] United States
• PMID: 14688622 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Isoenzymes
• Sulfonamides
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• nimesulide

Topics

• Animals
• Cell Death (physiology)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• DNA Fragmentation
• Hippocampus (pathology)
• Immunohistochemistry
• Ischemic Attack, Transient (genetics, pathology)
• Isoenzymes (deficiency, genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neurons (pathology)
• Prostaglandin-Endoperoxide Synthases (deficiency, genetics, metabolism)
• Sulfonamides (pharmacology)
• Up-Regulation (physiology)