Ethyl pyruvate protects against blood-brain barrier damage and improves long-term neurological outcomes in a rat model of traumatic brain injury.
Ethyl pyruvate protects against blood-brain barrier damage and improves long-term neurological outcomes in a rat model of traumatic brain injury.
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丙酮酸乙酯可防止血脑屏障损伤并改善创伤性脑损伤大鼠模型的长期神经学结果。
DOI：
10.1111/cns.12366
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发表时间：
2015-04
影响因子：
5.5
通讯作者：
Gao YQ
中科院分区：
文献类型：
--
作者：
Shi H;Wang HL;Pu HJ;Shi YJ;Zhang J;Zhang WT;Wang GH;Hu XM;Leak RK;Chen J;Gao YQ
许多创伤性脑损伤（TBI）幸存者由于缺乏明确的治疗方法来减少TBI诱导的长期脑损伤而导致神经功能障碍和认知障碍。丙酮酸乙酯（EP）在几种急性脑损伤模型中显示出神经保护作用。因此，本研究探讨了EP对TBI后长期结局的潜在有益作用及其潜在机制。雄性成年大鼠进行单侧控制性皮质撞击损伤。在TBI后15 min和TBI后12、24、36、48和60 h再次腹腔注射EP。评估神经功能缺损、血脑屏障（BBB）完整性和神经炎症。EP改善感觉运动和认知功能，并改善脑组织损伤后28天。脑损伤后48 h，EP可明显减轻脑水肿和血脑屏障破坏。EP抑制了外周中性粒细胞产生基质金属蛋白酶（MMP）-9，并减少了脾脏中过度产生MMP-9的中性粒细胞的数量，因此减轻了MMP-9介导的BBB破坏。此外，EP在培养的小胶质细胞中发挥有效的抗炎作用，并抑制TBI后脑中炎症介质的升高。EP可能通过打破MMP-9介导的BBB破坏、神经炎症和长期脑损伤之间的恶性循环，赋予针对TBI的长期神经保护。
Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms. Male adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity and neuroinflammation were assessed. EP improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 d post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent anti-inflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI. EP confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation and long-lasting brain damage.
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DOI：
10.1165/rcmb.2007-0330oc
发表时间：
2008-10-01
影响因子：
6.4
作者：
Hamada, Naoki;Maeyama, Takashige;Nakanishi, Yoichi
通讯作者：
Nakanishi, Yoichi
影响因子：
11.2
作者：
Ramlackhansingh, Anil F.;Brooks, David J.;Sharp, David J.
通讯作者：
Sharp, David J.
影响因子：
4.2
作者：
AIHARA, N;HALL, JJ;NOBLE, LJ
通讯作者：
NOBLE, LJ
影响因子：
3
作者：
Metz, GA;Whishaw, IQ
通讯作者：
Whishaw, IQ
HSP27可保护血脑屏障免受缺血诱导的完整性丧失。
DOI：
10.2174/1871527311312030006
发表时间：
2013-05-01
期刊：
CNS & neurological disorders drug targets
影响因子：
--
作者：
Leak RK;Zhang L;Stetler RA;Weng Z;Li P;Atkins GB;Gao Y;Chen J
通讯作者：
Chen J