PROGRESSIVE LOSS OF PHASIC, BUT NOT TONIC, GABAA RECEPTOR-MEDIATED INHIBITION IN DENTATE GRANULE CELLS IN A MODEL OF POST-TRAUMATIC EPILEPSY IN RATS
PROGRESSIVE LOSS OF PHASIC, BUT NOT TONIC, GABAA RECEPTOR-MEDIATED INHIBITION IN DENTATE GRANULE CELLS IN A MODEL OF POST-TRAUMATIC EPILEPSY IN RATS
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DOI：
10.1016/j.neuroscience.2011.07.074
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发表时间：
2011-10-27
期刊：
影响因子：
3.3
通讯作者：
Walker, M. C.
中科院分区：
文献类型：
--
作者：
Pavlov, I.;Huusko, N.;Walker, M. C.
创伤性脑损伤（TBI）是癫痫发展的危险因素，可在损伤后数月至数年发生。海马体特别容易受到创伤性脑损伤的病理生理影响。在这里，我们确定齿状回的抑制是否存在长期变化，这可能有助于TBI后癫痫发作的进行性易感性。我们采用严重外侧液体冲击脑损伤诱导大鼠TBI。在这个模型中，自发的癫痫发作活动，包括海马体，在很长一段潜伏期后出现，类似于人类的情况。我们证明，脑损伤后1个月，同侧齿状颗粒细胞突触GAB(A)受体介导的抑制显著降低。此外，突触抑制随着时间的推移而减少，到TBI后6个月，对侧也明显减少。突触抑制的逐渐丧失与小白蛋白阳性中间神经元数量的下降是平行的，但是，与癫痫持续状态模型相反，GABA(a)受体亚基的表达在很大程度上没有改变。在这两个时间点，TBI后强直GABA(A)受体介导的电流的大小保持不变，表明通过强直抑制保留了颗粒细胞的抑制约束。我们的结果延长了针对癫痫发生的策略可能有效的时间窗口。(c) 2011 ibro。Elsevier Ltd.出版。版权所有。
Traumatic brain injury (TBI) is a risk factor for the development of epilepsy, which can occur months to years after the insult. The hippocampus is particularly vulnerable to the pathophysiological effects of TBI. Here, we determined whether there are long-term changes in inhibition in the dentate gyrus that could contribute to the progressive susceptibility to seizures after TBI. We used severe lateral-fluid percussion brain injury to induce TBI in rats. In this model, spontaneous seizure activity, which involves the hippocampus, appears after a long latent period, resembling the human condition. We demonstrate that synaptic GAB(A), receptor-mediated inhibition is profoundly reduced in ipsilateral dentate granule cells 1 month after TBI. Moreover, synaptic inhibition decreases over time, and by 6 months after TBI, it is also significantly decreased contralaterally. Progressive loss of synaptic inhibition is paralleled by a decline in the number of parvalbumin-positive interneurons, but, in contrast to status epilepticus models, GABA(A) receptor subunit expression is largely unaltered. At both time points, the magnitude of tonic GABA(A) receptor-mediated currents after TBI is maintained, indicating a preservation of the inhibitory constraint of granule cells through tonic inhibition. Our results extend the time window during which strategies to target epileptogenesis may be effective. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.