Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice
Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice
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DOI：
10.3390/ijms20246125
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发表时间：
2019-12-01
影响因子：
5.6
通讯作者：
Wang, Xiaoying
中科院分区：
文献类型：
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作者：
Liu, Ning;Jiang, Yinghua;Wang, Xiaoying
我们的实验室和其他实验室先前表明，Annexin A2敲除（A2KO）小鼠的血脑屏障（BBB）发育受损，巨噬细胞中的促炎反应升高，这意味着Annexin A2（AnxA2）可能是维持脑中神经血管单位稳态的关键内源性因素之一。创伤性脑损伤（Traumatic brain injury，TBI）是世界范围内致残和致死的重要原因，而神经血管炎症在TBI的病理生理中起着重要作用。在本研究中，我们的目的是测试的假设，即A2 KO促进促炎症反应在大脑和TBI后的神经行为的结果。通过受控皮质撞击（CCI）装置在小鼠中进行TBI。我们的实验结果表明，AnxA2的表达显着上调TBI后3天响应TBI。我们还发现在A2KO小鼠脑中产生更多的促炎细胞因子，而与野生型（WT）小鼠相比，A2KO小鼠的分离脑微血管中炎性粘附分子mRNA表达显著增加。因此，A2KO小鼠脑在TBI后两天具有显著的白细胞脑浸润增加。重要的是，A2KO小鼠在TBI后28天内具有显著更差的感觉运动和认知功能缺陷以及显著更大的脑组织损失。因此，这些结果表明，AnxA2缺乏导致早期神经血管促炎症加剧，这导致TBI后长期神经功能结局更差。
Our laboratory and others previously showed that Annexin A2 knockout (A2KO) mice had impaired blood-brain barrier (BBB) development and elevated pro-inflammatory response in macrophages, implying that Annexin A2 (AnxA2) might be one of the key endogenous factors for maintaining homeostasis of the neurovascular unit in the brain. Traumatic brain injury (TBI) is an important cause of disability and mortality worldwide, and neurovascular inflammation plays an important role in the TBI pathophysiology. In the present study, we aimed to test the hypothesis that A2KO promotes pro-inflammatory response in the brain and worsens neurobehavioral outcomes after TBI. TBI was conducted by a controlled cortical impact (CCI) device in mice. Our experimental results showed AnxA2 expression was significantly up-regulated in response to TBI at day three post-TBI. We also found more production of pro-inflammatory cytokines in the A2KO mouse brain, while there was a significant increase of inflammatory adhesion molecules mRNA expression in isolated cerebral micro-vessels of A2KO mice compared with wild-type (WT) mice. Consistently, the A2KO mice brains had a significant increase in leukocyte brain infiltration at two days after TBI. Importantly, A2KO mice had significantly worse sensorimotor and cognitive function deficits up to 28 days after TBI and significantly larger brain tissue loss. Therefore, these results suggested that AnxA2 deficiency results in exacerbated early neurovascular pro-inflammation, which leads to a worse long-term neurologic outcome after TBI.