Administration of COG1410 Reduces Axonal Amyloid Precursor Protein Immunoreactivity and Microglial Activation after Controlled Cortical Impact in Mice
Administration of COG1410 Reduces Axonal Amyloid Precursor Protein Immunoreactivity and Microglial Activation after Controlled Cortical Impact in Mice
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小鼠受控皮质影响后，给予 COG1410 可降低轴突淀粉样前体蛋白免疫反应性和小胶质细胞活化
DOI：
10.1089/neu.2012.2362
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Brody, David L.
中科院分区：
文献类型：
--
作者：
Jiang, Yong;Brody, David L.
在无占位性病变的创伤性脑损伤 (TBI) 患者中，创伤性轴索损伤 (TAI) 的发病率和死亡率至少占 35%。它也被认为是不良后果的关键决定因素，例如跨 TBI 严重程度的认知功能障碍。先前的研究表明，COG1410 是一种源自载脂蛋白 E (apoE) 受体结合区的合成肽，在实验性 TBI 后具有抗炎作用，并能改善认知恢复。然而，COG1410 对 TBI 后轴突损伤的影响尚不清楚。目前的研究评估了在年轻野生型 C57BL6/J 雄性小鼠中，控制性皮质撞击 (CCI) 损伤后 30 分钟开始，每日 1 mg/kg COG1410 与静脉注射生理盐水相比，对挫伤周围 TAI 的影响。我们发现，COG1410 不会影响 24 小时时胼胝体周围和外囊中淀粉样前体蛋白 (APP) 免疫反应性轴突静脉曲张的数量，但在 3 天时使 APP 免疫反应性静脉曲张减少 31%（p = 0.0023），在 7 天时减少 36%（p = 0.0009）。 COG1410 在所有三个时间点均显着减少了具有激活小胶质细胞形态的 Iba1 阳性细胞数量 21-30%。 COG1410 在任何时间点对挫伤周围白质体积或银染色均没有影响。这表明 COG1410 对延迟 TAI 可能有影响，但不会立即产生影响。未来的研究需要调查这种效应的潜在机制、治疗时间窗和生理影响。
Traumatic axonal injury (TAI) accounts for at least 35% of the morbidity and mortality in traumatic brain injury (TBI) patients without space-occupying lesions. It is also believed to be a key determinant of adverse outcomes such as cognitive dysfunction across the spectrum of TBI severity. Previous studies have shown that COG1410, a synthetic peptide derived from the apolipoprotein E (apoE) receptor binding region, has anti-inflammatory effects after experimental TBI, with improvements in cognitive recovery. However, the effects of COG1410 on axonal injury following TBI are not known. The current study evaluated the effects of 1 mg/kg daily COG1410 versus saline administered intravenously starting 30 min after controlled cortical impact (CCI) injury on pericontusional TAI in young, wild-type C57BL6/J male mice. We found that COG1410 did not affect the number of amyloid precursor protein (APP)-immunoreactive axonal varicosities in the pericontusional corpus callosum and external capsule at 24 h, but reduced APP-immunoreactive varicosities by 31% at 3 days (p = 0.0023), and 36% at 7 days (p = 0.0009). COG1410 significantly reduced the number of Iba1-positive cells with activated microglial morphology at all three time points by 21-30%. There was no effect of COG1410 on pericontusional white matter volume or silver staining at any time point. This indicates a possible effect of COG1410 on delayed but not immediate TAI. Future studies are needed to investigate the underlying mechanisms, therapeutic time window, and physiological implications of this effect.