Treatment of intracerebral hemorrhage in rats with 12 h, 3 days and 6 days of selective brain hypothermia.
Intracerebral hemorrhage (ICH) is a devastating stroke with no proven treatment to reduce brain injury. In this study we modeled ICH by injecting 100 microL of autologous blood into the striatum of rats. We then tested whether hypothermia would reduce brain injury and improve recovery as has been repeatedly observed for ischemic and traumatic brain damage. Aside from reducing blood-brain barrier disruption, inflammation and edema, hypothermia has not consistently improved behavioral or histological outcome after ICH in animal studies. As this might relate to the choice of cooling method and the duration of hypothermia, we used a system that selectively cooled the injured hemisphere to approximately 32 degrees C (striatum) while the body remained normothermic. Cooling (vs. normothermia) started 1 h after ICH and lasted for 12 h, 3 days or 6 days followed by slow re-warming (approximately 1 degrees C/h). Functional impairment was evaluated from 2 to 3 weeks post-ICH at which time brain injury was determined. The ICH caused significant impairment on a neurological deficit scale and in tests of walking (horizontal ladder), skilled reaching (tray task) and spontaneous limb usage (cylinder test). Only the limb use asymmetry deficit was significantly mitigated by hypothermia, and then only by the longest treatment. Lesion volume, which averaged 16.9 mm3, was not affected. These results, in conjunction with earlier studies, suggest that prolonged mild hypothermia will not be a profound neuroprotectant for patients with striatal ICH, but it may nonetheless improve functional recovery in addition to its use for treating cerebral edema.
Fingas
Matthew
M
Centre for Neuroscience, University of Alberta, Edmonton, AB, Canada.
Penner
Mark
M
Silasi
Gergely
G
Colbourne
Frederick
F
D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001929:Brain Edema / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019610:Cytoprotection / Q000502:physiology; D004195:Disease Models, Animal; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D009069:Movement Disorders / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D017694:Rewarming / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome