Glucocorticoids Aggravate Retrograde Memory Deficiency Associated with Traumatic Brain Injury in Rats
Glucocorticoids Aggravate Retrograde Memory Deficiency Associated with Traumatic Brain Injury in Rats
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DOI：
10.1089/neu.2007.0504
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发表时间：
2009-02-01
影响因子：
4.2
通讯作者：
Zhang, Jian-Ning
中科院分区：
文献类型：
--
作者：
Chen, Xin;Zhang, Ke-Li;Zhang, Jian-Ning
对头部损伤患者使用糖皮质激素以前已被证明会损害记忆。我们假设糖皮质激素促进创伤后海马细胞凋亡，导致与创伤性脑损伤（TBI）相关的逆行性记忆缺陷。在本研究中，我们通过测量遭受液压冲击损伤（FPI）并接受地塞米松（DXM，0.5-10 mg/kg）或甲基强的松龙（MP，5-30 mg/kg）的大鼠的空间记忆缺陷来验证这一假设;我们还检查了海马中的神经元凋亡。训练成年雄性Wistar大鼠获得空间记忆，然后进行FPI，并在损伤后第7天和第14天使用Morris水迷宫测试空间参考记忆。伤后24 h ~ 2周取脑组织行病理学检查。在目标象限的百分比时间，测量空间参考记忆，是显着低于受伤的大鼠接受高剂量DXM或MP比对照组。海马TUNEL阳性细胞在损伤后24 h首次检测到，48 h达到平台。TUNEL阳性细胞的数量显着较高，无论是DXM或MP治疗的损伤大鼠。这些数据表明，糖皮质激素治疗TBI可能会增加海马神经元凋亡，从而加重TBI引起的逆行记忆障碍。
Administration of glucocorticoid to patients with head injury has previously been demonstrated to impair memory. We hypothesize that glucocorticoids promote post-traumatic hippocampal apoptosis, resulting in retrograde memory deficiency associated with traumatic brain injury (TBI). In the present study, we tested this hypothesis by measuring spatial memory deficiency in rats subjected to fluid percussion injury (FPI) and receiving dexamethasone (DXM at 0.5-10 mg/kg) or methylprednisolone (MP at 5-30 mg/kg); we also examined neuronal apoptosis in hippocampus. Adult male Wistar rats were trained for the acquisition of spatial memory, then subjected to FPI and tested for spatial reference memory on post-injury days 7 and 14 using the Morris Water Maze. Brain tissue from injured rats was examined 24 h to 2 weeks after injury. The percent time in the goal quadrant, which measures spatial reference memory, was significantly lower in injured rats receiving either high-dose DXM or MP than in control groups. TUNEL-positive cells in hippocampus were first detected 24 h post-injury, plateauing at 48 h. The number of TUNEL-positive cells was significantly higher in injured rats treated with either DXM or MP. The data suggest that glucocorticoid therapy for TBI may increase neuronal apoptosis in hippocampus and, as a result, aggravate retrograde memory deficits induced by TBI.