title: Caveolin-1 deletion reduces early brain injury after experimental intracerebral hemorrhage.
abstract: Intracerebral hemorrhage (ICH) is a subtype of stroke with high rates of morbidity and mortality. Caveolin-1 (Cav-1) is the main structural protein of caveolae and is involved in regulating signal transduction and cholesterol trafficking in cells. Although a recent study suggests a protective role of Cav-1 in cerebral ischemia, its function in ICH remains unknown. In this study, we examined the role of Cav-1 and in a model of collagenase-induced ICH and in neuronal cultures. Our results indicate that Cav-1 was up-regulated in the perihematomal area predominantly in endothelial cells. Cav-1 knockout mice had smaller injury volumes, milder neurologic deficits, less brain edema, and neuronal death 1 day after ICH than wild-type mice. The protective mechanism in Cav-1 knockout mice was associated with marked reduction in leukocyte infiltration, decreased expression of inflammatory mediators, including macrophage inflammatory protein (MIP)-2 and cyclooxygenase (COX)-2, and reduced matrix metalloproteinase-9 activity. Deletion of Cav-1 also suppressed heme oxygenase-1 expression and attenuated reactive oxygen species production after ICH. Moreover, deletion or knockdown of Cav-1 decreased neuronal vulnerability to hemin-induced toxicity and reduced heme oxygenase (HO)-1 induction in vitro. These data suggest that Cav-1 plays a deleterious role in early brain injury after ICH. Inhibition of Cav-1 may provide a novel therapeutic approach for the treatment of hemorrhagic stroke.
authors: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors: Che-Feng
authors: CF
authors: Chang
authors: Shu-Fen
authors: SF
authors: Chen
authors: Tzong-Shyuan
authors: TS
authors: Lee
authors: Hung-Fu
authors: HF
authors: Lee
authors: Szu-Fu
authors: SF
authors: Chen
authors: Song-Kun
authors: SK
authors: Shyue
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000235:genetics*; D051242:Caveolin 1 / Q000235:genetics*; D002543:Cerebral Hemorrhage / Q000235:genetics*; D004195:Disease Models, Animal; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D020521:Stroke / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D017382:Reactive Oxygen Species