Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury
Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury
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DOI：
10.1523/jneurosci.1898-15.2016
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发表时间：
2016-09-21
影响因子：
5.3
通讯作者：
Sheng, Morgan
中科院分区：
文献类型：
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作者：
Ertuerk, Ali;Mentz, Susanne;Sheng, Morgan
创伤性脑损伤（TBI）后，在最初的损伤中幸存下来的神经元可能会通过知之甚少的机制经历慢性（继发性）退化，从而导致长期认知障碍。尽管神经炎症反应在 TBI 后迅速激活，但尚不清楚它是否在 TBI 慢性期（损伤后 > 1 年）中发挥重要作用。使用小鼠 TBI 的闭合性头部损伤模型，我们通过 MRI 扫描表明，TBI 在几周内引起病变部位的严重退化，并且此后这些病变并没有显着扩大。然而，观察到神经元的慢性改变，树突棘密度降低在损伤后持续> 1年。与此同时，我们发现整个大脑存在持久的炎症反应。 CX(3)CR1（一种趋化因子受体）的一个等位基因的缺失，限制了外周免疫细胞的浸润，并在很大程度上防止了受损大脑的慢性退化，并为雌性（而非雄性）小鼠提供了更好的功能恢复。因此，针对持续性神经炎症提供了减少慢性神经退行性变的新治疗选择。
After traumatic brain injury (TBI), neurons surviving the initial insult can undergo chronic (secondary) degeneration via poorly understood mechanisms, resulting in long-term cognitive impairment. Although a neuroinflammatory response is promptly activated after TBI, it is unknown whether it has a significant role in chronic phases of TBI (> 1 year after injury). Using a closed-head injury model of TBI in mice, we showed by MRI scans that TBI caused substantial degeneration at the lesion site within a few weeks and these did not expand significantly thereafter. However, chronic alterations in neurons were observed, with reduced dendritic spine density lasting > 1 year after injury. In parallel, we found a long-lasting inflammatory response throughout the entire brain. Deletion of one allele of CX(3)CR1, a chemokine receptor, limited infiltration of peripheral immune cells and largely prevented the chronic degeneration of the injured brain and provided a better functional recovery in female, but not male, mice. Therefore, targeting persistent neuroinflammation presents a new therapeutic option to reduce chronic neurodegeneration.