The Association of Cigarette Smoking with Stroke Outcome in Rats with Intracerebral Hemorrhage

Hypertensive intracerebral hemorrhage (ICH) represents at least 15% of all strokes in Western populations and a considerably higher proportion (20% to 30%) in Asian and black populations. The prognosis of hemorrhagic stroke is poor, often much worse than that of ischemic stroke of similar size. Primary injury after ICH results from the mass effect of the hematoma and needs invasive evacuation of hematoma immediately in selective patients. The peak of ICH-induced death within the first few days following ictus is likely to be associated with secondary brain damage. It is thought to arise from tissue reaction to invasion of blood products in the area around the hematoma, resulting in ischemia, edema formation and inflammatory response. The exact mechanism of edema formation after ICH is still not clear. It is possible that disruption of the blood-brain barrier (BBB), focal ischemia by disturbance of microcirculation, toxicity of hemoglobin and/or free radicals delivered from hemolysate, thrombin production and elevation of local osmolarity by exudates can contribute to the formation of perifocal edema in ICH. Current experimental evidence also demonstrates that an inflammatory response plays an important part in ICH-induced injury. The infiltration of inflammatory cells and proliferation of astrocytes are observed around the ICH. These polymorphonuclears produce free radicals such as peroxynitrite and oxygen radicals, which impair cell function including deoxyribonucleic acid level in neurons and oligodendroglia. Inflammatory cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor-α may open BBB and result in brain edema. Cigarette smoking places a tremendous burden on health resources throughout the world and is an increasingly important public health issue. Chronic cigarette smoking can increase vascular superoxide production and blunt nitric oxide (NO)-induced vasodilatation of pial vessels. Cigarette smoking also impair endothelium-dependent vasorelaxation and is thought a significant risk factor for ischemic stroke. However, the cigarette smoking influences on hypertensive ICH outcome are still unclear and little investigated. In this project, male Sprague-Dawley rats are exposed to chronic cigarette smoking for 50 mins/day (a total of 100 puffs/day), 6 days a week for 4 weeks. The purpose of this study is to examine whether chronic cigarette smoking affects the outcome of hypertensive ICH by influencing peri-ICH microenvironment, local BBB changes, inflammatory responses, free radicals production and the corresponding apoptosis in the ICH-induced brain injury.

Project ID:PC9902-1680
External Project ID:NSC98-2314-B182-025-MY2