Neuroprotective effect of ceftriaxone in a rat model of traumatic brain injury
Neuroprotective effect of ceftriaxone in a rat model of traumatic brain injury
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DOI：
10.1007/s10072-013-1585-4
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发表时间：
2014-05-01
影响因子：
3.3
通讯作者：
Cui, Jianzhong
中科院分区：
文献类型：
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作者：
Cui, Changmeng;Cui, Ying;Cui, Jianzhong
创伤性脑损伤 (TBI) 是全世界儿童和年轻人死亡和残疾的主要原因。神经损伤是由脑组织立即破坏和损伤后细胞和分子事件引起的，这些事件会加重原发性神经损伤。据报道，β-内酰胺类抗生素头孢曲松 (CTX) 可通过上调 GLT-1 在多种神经系统疾病的动物模型中诱导神经保护作用。然而，尚无研究探讨 CTX 在 TBI 中的神经保护作用，并且该机制是否参与神经元自噬的调节仍完全不清楚。本研究旨在确定以下假设：给予 CTX 可以显着增强 TBI 大鼠模型的功能恢复，以及 CTX 治疗是否可以上调 GLT-1 表达并抑制 TBI 后神经元自噬。结果表明，每日使用 CTX 治疗可减轻 TBI 引起的大鼠脑水肿和认知功能缺陷。 GLT-1 在 TBI 后下调，这种现象可以通过 CTX 治疗来逆转。此外，我们还发现与TBI组相比，CTX显着减少了海马中的自噬标记蛋白LC3 II。这些结果表明，CTX 可能为 TBI 提供一种新的治疗策略，这种保护可能与 GLT-1 的上调和神经元自噬的抑制有关。
Traumatic brain injury (TBI) is a leading cause of mortality and disability in children and young adults worldwide. Neurologic impairment is caused by both immediate brain tissue disruption and post-injury cellular and molecular events that worsen the primary neurologic insult. The beta-lactam antibiotic ceftriaxone (CTX) has been reported to induce neuroprotection in animal models of diverse neurologic diseases via up-regulation of GLT-1. However, no studies have addressed the neuroprotective role of CTX in the setting of TBI, and whether the mechanism is involved in the modulation of neuronal autophagy remains totally unclear. The present study was designed to determine the hypothesis that administration of CTX could significantly enhance functional recovery in a rat model of TBI and whether CTX treatment could up-regulate GLT-1 expression and suppress post-TBI neuronal autophagy. The results demonstrated that daily treatment with CTX attenuated TBI-induced brain edema and cognitive function deficits in rats. GLT-1 is down-regulated following TBI and this phenomenon can be reversed by treatment of CTX. In addition, we also found that CTX significantly reduced autophagy marker protein, LC3 II, in hippocampus compared to the TBI group. These results suggest that CTX might provide a new therapeutic strategy for TBI and this protection might be associated with up-regulation of GLT-1 and suppression of neuronal autophagy.