Postischemic hypothermia and IL-10 treatment provide long-lasting neuroprotection of CA1 hippocampus following transient global ischemia in rats
Postischemic hypothermia and IL-10 treatment provide long-lasting neuroprotection of CA1 hippocampus following transient global ischemia in rats
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DOI：
10.1006/exnr.1999.7115
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发表时间：
1999-08-01
影响因子：
5.3
通讯作者：
Bethea, JR
中科院分区：
文献类型：
--
作者：
Dietrich, WD;Busto, R;Bethea, JR
实验研究表明，缺血后的治疗干预可能会延迟而不是提供长期的神经保护。本研究的目的是确定亚低温(33-34℃)联合抗炎细胞因子白介素10(IL-10)对缺血2个月后的CA1区海马区是否具有保护作用。采用双血管结扎法造成大鼠常温(37℃)前脑缺血12.5min，然后立即给予常温(37℃)再灌注4h(n=5)，(B)缺血后低温(33~34℃)4h(n=5)，(C)缺血30min后3d(n=5)常温4h+IL-10治疗(n=5)，或(D)低温+IL-10治疗4h(n=5)。大鼠存活2个月，灌流固定后进行CA1区海马区的定量组织病理学评价。缺血后常温、低温以及常温+IL-10治疗可导致CA1区海马区严重损伤。相比之下，与常温缺血相比，低温与IL-10联合治疗可使神经元总存活率提高49%(P<；0.01)。这些数据强调了短暂性全脑缺血后继发性炎症反应对缺血性神经元损伤的有害后果。在损伤后的环境中，可以诱导有限时间的亚低温，包括IL-10在内的抗炎治疗可能会促进慢性神经保护。(C)1999年学术出版社。
Experimental studies have demonstrated that postischemic therapeutic interventions may delay rather than provide long-lasting neuroprotection. The purpose of this study was to determine whether mild hypothermia (33-34 degrees C) combined with the anti-inflammatory cytokine interleukin-10 (IL-10) would protect the CA1 hippocampus 2 months after ischemia. Rats were subjected to 12.5 min of normothermic (37 degrees C) forebrain ischemia by two-vessel occlusion followed immediately by: (a) 4 h of normothermic (37 degrees C) reperfusion (n = 5); (b) 4 h of postischemic hypothermia (33-34 degrees C) (n = 5); (c) 4 h of normothermia plus IL-10 (5 mu g) treatment 30 min after ischemia and at 3 days (n = 5); or (d) 4 h of hypothermia plus IL-10 treatment (n = 5). Rats survived for 2 months and were perfusion fixed for quantitative histopathological assessment of CA1 hippocampus. Postischemic normothermia and hypothermia, as well as normothermia plus IL-10 treatment led to severe damage of the CA1 hippocampus. In contrast, the combined treatment of hypothermia with IL-10 treatment improved overall neuronal survival by 49% compared to normothermic ischemia (P < 0.01). These data emphasize the detrimental consequences of secondary inflammatory responses on ischemic neuronal damage after transient global ischemia. In postinjury settings where restricted durations of mild hypothermia can be induced, anti-inflammatory treatments, including IL-10, may promote chronic neuroprotection. (C) 1999 Academic Press.