Insulin-like growth factor-1 improves somatosensory function and reduces the extent of cortical infarction and ongoing neuronal loss after hypoxia-ischemia in rats
Insulin-like growth factor-1 improves somatosensory function and reduces the extent of cortical infarction and ongoing neuronal loss after hypoxia-ischemia in rats
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DOI：
10.1016/s0306-4522(01)00145-2
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Gluckman, PD
中科院分区：
文献类型：
--
作者：
Guan, J;Miller, OT;Gluckman, PD
胰岛素样生长因子-1的治疗已经被证明可以减少缺氧缺血性脑损伤后5天的皮质梗塞的范围。由于早期损伤后神经元的死亡可以是进行性的和持久的，本研究观察了胰岛素样生长因子-1对缺氧缺血性损伤后20天迟发性神经元丢失的长期影响，并评估了体感功能假设的神经行为结果。损伤后2小时，单次注射胰岛素样生长因子-1(50µg)，经立体定向插管注入侧脑室。用双侧触觉刺激试验检测胰岛素样生长因子-1治疗组(n=12)及其载体组(n=12)和假手术组(n=9)缺氧后3，5，10，20d体感功能的变化。两个治疗组在缺氧缺血20天后检测皮质梗塞和选择性神经元丢失的百分比。与假手术大鼠(1.1+/0.9，P<；0.05)相比，缺氧缺血损伤导致在观察期间内接触补片的时间显著延迟(左/右比率5.1+/-0.79)，尤其是在缺氧后3天(7.0+/-2.8)。与赋形剂组相比，胰岛素样生长因子-1在减少贴片接触时间方面的总体效果显著(P=0.03，2.6+/-0.79)。给予胰岛素样生长因子-1治疗后，皮质梗塞有减少的趋势(P=0.058)，但胰岛素样生长因子-1显著降低了缺氧20d后选择性神经元丢失的百分比(P=0.027)。根据这些数据，我们认为胰岛素样生长因子-1通过在脑缺氧缺血损伤恢复过程中减少皮质梗塞的范围和持续的进行性神经元死亡来改善体感功能。(C)2001年IBRO。爱思唯尔科学有限公司出版。版权所有。
Treatment with insulin-like growth factor-1 has been demonstrated to reduce the extent of cortical infarction 5 days after hypoxic-ischemic, brain injury. As neuronal death can be progressive and long lasting after initial injury, the present study examined the long-term effects of insulin-like growth factor-1 on late neuronal loss 20 days after hypoxic-ischemic injury, together with evaluating neurobehavioral outcome as assumed by somatosensory function.Unilateral brain injury was induced in adult rats by carotid artery ligation followed by 10 min of hypoxia (6% O-2). A single dose of insulin-like growth factor-1 (50 mug) was administered intracerebroventricularly via a stereotaxically prefixed cannula 2 h after injury. A bilateral tactile stimulation test was used to examine the degree of somatosensory function at 3, 5, 10 and 20 days after the hypoxia in both insulin-like growth factor-1- (n = 12) and its vehicle- (n = 12) treated rats, along with sham-operated rats (n = 9). Cortical infarction and percentage of selective neuronal loss in the cerebral cortex were examined 20 days after the hypoxic-ischemic injury in both treatment groups.Hypoxic-ischemic injury resulted in a significant delay in the time taken to contact the patch over the period examined (left/right ratio 5.1 +/- 0.79), particularly at 3 days (7.0 +/- 2.8) after the hypoxia, compared to sham-operated rats (1.1 +/- 0.9, P < 0.05). The overall effect of insulin-like growth factor-1 in reducing the time taken to contact the patch was significant (P = 0.03, 2.6 +/- 0.79) compared to the vehicle group. There was a trend towards a reduction of cortical infarction after insulin-like growth factor-1 treatment (P = 0.058), however insulin-like growth factor-1 significantly reduced the percentage of selective neuronal loss (P = 0.027) 20 days following the hypoxia. From these data we suggest that insulin-like growth factor-1 improves somatosensory function by reducing both the extent of cortical infarction and ongoing progressive neuronal death during brain recovery from hypoxic-ischemic injury. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.