Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.
Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
Int J Mol Sci. 2022 Apr 9;23(8):4162. doi: 10.3390/ijms23084162.
Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB). Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI and to be overexpressed in the absence of apolipoprotein E (ApoE). Bevacizumab, a VEGF inhibitor, demonstrated neuroprotective activity in several models of TBI. However, the effects of bevacizumab on Apo-E deficient mice are not well studied. The present study aimed to evaluate VEGF expression and the effects of bevacizumab on BBB and neuroinflammation in ApoE mice undergoing TBI. Furthermore, for the first time, this study evaluates the effects of bevacizumab on the long-term consequences of TBI, such as atherosclerosis. The results showed that motor deficits induced by controlled cortical impact (CCI) were accompanied by increased brain edema and VEGF expression. Treatment with bevacizumab significantly improved motor deficits and significantly decreased VEGF levels, as well as brain edema compared to the control group. Furthermore, the results showed that bevacizumab preserves the integrity of the BBB and reduces the neuroinflammation induced by TBI. Regarding the effects of bevacizumab on atherosclerosis, it was observed for the first time that its ability to modulate VEGF in the acute phase of head injury prevents the acceleration of atherosclerosis. Therefore, the present study demonstrates not only the neuroprotective activity of bevacizumab but also its action on the vascular consequences related to TBI.
创伤性脑损伤（TBI）会破坏血脑屏障（BBB）。血管内皮生长因子（VEGF）被认为在 TBI 中起关键作用，并且在载脂蛋白 E（ApoE）缺乏的情况下过度表达。贝伐单抗是一种 VEGF 抑制剂，在几种 TBI 模型中显示出神经保护活性。然而，贝伐单抗对 Apo-E 缺陷小鼠的影响尚未得到很好的研究。本研究旨在评估 VEGF 表达以及贝伐单抗对 TBI 后 ApoE 小鼠 BBB 和神经炎症的影响。此外，本研究首次评估了贝伐单抗对 TBI 长期后果（如动脉粥样硬化）的影响。结果表明，经皮质控制冲击（CCI）引起的运动功能障碍伴随着脑水肿和 VEGF 表达增加。与对照组相比，贝伐单抗治疗显著改善了运动功能障碍，显著降低了 VEGF 水平和脑水肿。此外，结果表明，贝伐单抗可维持 BBB 的完整性并减轻 TBI 引起的神经炎症。关于贝伐单抗对动脉粥样硬化的影响，首次观察到其在头部损伤急性期调节 VEGF 的能力可防止动脉粥样硬化的加速。因此，本研究不仅证明了贝伐单抗的神经保护活性，还证明了其对与 TBI 相关的血管后果的作用。
