Mild traumatic brain injury-induced persistent blood-brain barrier disruption is prevented by cyclosporine A treatment in hypertension.
Mild traumatic brain injury-induced persistent blood-brain barrier disruption is prevented by cyclosporine A treatment in hypertension.
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DOI：
10.3389/fneur.2023.1252796
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发表时间：
2023
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
轻度创伤性脑损伤（mTBI）和高血压协同作用，诱导血脑屏障（BBB）的持续破坏，神经炎症和认知能力下降。然而，其潜在机制尚不清楚。亲环素A（CyPA）在高血压和TBI后诱导脑产生，并且已证明它激活脑血管中的核因子-κB（NF-kB）-基质金属蛋白酶-9（MMP-9）途径，导致BBB破坏。为了测试CyPA在mTBI和高血压诱导的BBB破坏中的作用，我们在正常血压和自发性高血压大鼠（SHR）中诱导mTBI，然后用环孢霉素A（CyPA产生的特异性抑制剂）或载体处理动物7天。我们评估了血脑屏障的渗透性和完整性，脑内CyPA-NF-kB-MMP-9通路的表达和活性，纤维蛋白外渗和神经炎症。我们发现，轻度TBI诱导高血压中BBB破坏和CyPA-NF-kB-MMP-9通路的上调，阻断CyPA可以防止这一点。环孢霉素治疗和血脑屏障功能的保护防止了mTBI后高血压大鼠脑实质中血液来源的纤维蛋白的积累，并逆转了增加的神经炎症。我们认为，mTBI和高血压相互作用，促进血脑屏障破坏通过CyPA-NF-kB-MMP-9途径，抑制亲环素的生产后mTBI可能发挥神经保护作用，改善高血压患者的认知功能。
Mild traumatic brain injury (mTBI) and hypertension synergize to induce persistent disruption of the blood–brain barrier (BBB), neuroinflammation and cognitive decline. However, the underlying mechanisms are not known. Cerebral production of Cyclophilin A (CyPA) is induced in hypertension and after TBI, and it was demonstrated to activate the nuclear factor-κB (NF-kB)- matrix-metalloproteinase-9 (MMP-9) pathway in cerebral vessels leading to BBB disruption. To test the role of CyPA in mTBI- and hypertension-induced BBB disruption we induced mTBI in normotensive and spontaneously hypertensive rats (SHR), then the animals were treated with cyclosporine A (a specific inhibitor of CyPA production) or vehicle for 7 days. We assessed BBB permeability and integrity, cerebral expression and activity of the CyPA-NF-kB-MMP-9 pathway, extravasation of fibrin and neuroinflammation. We found that mild TBI induced BBB disruption and upregulation of the CyPA-NF-kB-MMP-9 pathway in hypertension, which were prevented by blocking CyPA. Cyclosporine treatment and preservation of BBB function prevented accumulation of blood-derived fibrin in the brain parenchyma of hypertensive rats after mTBI and reversed increased neuroinflammation. We propose that mTBI and hypertension interact to promote BBB disruption via the CyPA-NF-kB-MMP-9 pathway, and inhibition of cyclophilin production after mTBI may exert neuroprotection and improve cognitive function in hypertensive patients.
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影响因子：
8.3
作者：
Candelario-Jalil E;Thompson J;Taheri S;Grossetete M;Adair JC;Edmonds E;Prestopnik J;Wills J;Rosenberg GA
通讯作者：
Rosenberg GA
DOI：
10.1073/pnas.89.8.3511
发表时间：
1992-04-15
影响因子：
11.1
作者：
SHERRY, B;YARLETT, N;CERAMI, A
通讯作者：
CERAMI, A
影响因子：
2.4
作者：
Rutland-Brown, Wesley;Langlois, Jean A.;Lily, Yongli
通讯作者：
Lily, Yongli
影响因子：
4.2
作者：
O'Keeffe, Eoin;Kelly, Eoin;Campbell, Matthew
通讯作者：
Campbell, Matthew
影响因子：
2.9
作者：
Bodo, Kornelia;Boros, Akos;Engelmann, Peter
通讯作者：
Engelmann, Peter