MacLellan Crystal L, Davies Laura M, Fingas Matthew S, Colbourne Frederick
Department of Psychology, University of Alberta, Edmonton, Alberta, Canada.
Stroke. 2006 May;37(5):1266-70. doi: 10.1161/01.STR.0000217268.81963.78. Epub 2006 Mar 30.
Late hypothermia (HYPO) reduces injury after collagenase-induced intracerebral hemorrhage (ICH), whereas early HYPO does not because it exacerbates the protracted bleeding that occurs in this model. We hypothesized that early HYPO would not increase bleeding after whole blood infusion and thus expected early HYPO to improve outcome through reducing secondary consequences of ICH (eg, inflammation).
Autologous blood (100 microL) was infused into the striatum. Rats were maintained at normothermia or subjected to mild (33 degrees C to 35 degrees C) HYPO for 2 days starting 1 (HYPO-1) or 4 hours (HYPO-4) after ICH. Hematoma volume was measured at 12 hours to determine whether HYPO-1 aggravated bleeding. We measured blood-brain barrier (BBB) disruption and edema 2 days after ICH in all groups. At 4 days, we counted degenerating neurons, neutrophils, and iron-positive cells (eg, macrophages) in the lesioned hemisphere. Recovery was assessed using several behavioral tests (ie, staircase reaching task, ladder walking task, limb use cylinder test) over 7 or 30 days, at which time we quantified lesion volume.
HYPO did not increase bleeding. Both HYPO treatments reduced BBB disruption and infiltration of inflammatory cells. HYPO-1 treatment modestly reduced edema and provided limited to no functional benefit in the behavioral tests. HYPO did not affect lesion volume.
HYPO reduced edema, BBB disruption, and inflammation. Although encouraging, HYPO treatment must be improved so that histological and functional benefit are obtained before clinical investigation. Otherwise clinical failure is anticipated.
迟发性低温可减轻胶原酶诱导的脑出血(ICH)后的损伤,而早期低温则不然,因为它会加剧该模型中发生的持续性出血。我们假设早期低温不会增加全血输注后的出血,因此预期早期低温可通过减少ICH的继发性后果(如炎症)来改善预后。
将自体血(100微升)注入纹状体。大鼠在正常体温下维持,或在脑出血后1小时(低温-1组)或4小时(低温-4组)开始接受轻度(33℃至35℃)低温处理2天。在12小时时测量血肿体积,以确定低温-1组是否会加重出血。我们在脑出血后2天测量所有组的血脑屏障(BBB)破坏和水肿情况。在4天时,我们对损伤半球中的变性神经元、中性粒细胞和铁阳性细胞(如巨噬细胞)进行计数。在7天或30天内使用多种行为测试(即阶梯够物任务、梯子行走任务、肢体使用圆柱体测试)评估恢复情况,此时我们对损伤体积进行量化。
低温并未增加出血。两种低温处理均减少了BBB破坏和炎性细胞浸润。低温-1组治疗适度减轻了水肿,在行为测试中提供了有限或无功能益处。低温对损伤体积无影响。
低温减轻了水肿、BBB破坏和炎症。尽管令人鼓舞,但必须改进低温治疗,以便在临床研究之前获得组织学和功能益处。否则预计会出现临床失败。