3,6'-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury.
3,6'-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury.
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DOI：
10.3390/ijms22158276
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发表时间：
2021-07-31
影响因子：
5.6
通讯作者：
Wang JY
中科院分区：
文献类型：
--
作者：
Huang PS;Tsai PY;Yang LY;Lecca D;Luo W;Kim DS;Hoffer BJ;Chiang YH;Greig NH;Wang JY
创伤性脑损伤（TBI）是世界范围内导致残疾和死亡的主要原因。它可以引发立即的细胞死亡，然后是时间依赖性的继发性损伤，这是由脑组织中不成比例的小胶质细胞和星形胶质细胞活化、过度炎症和氧化应激引起的，最终导致短期和长期的认知功能障碍和行为缺陷。在大脑中，海马体特别容易受到TBI的影响。我们研究了一种新的泊马度胺（Pom）类似物3，6 ′-二硫代泊马度胺（DP）和泊马度胺作为免疫调节酰亚胺药物（IMiD）对TBI诱导的大鼠海马神经元变性、小胶质细胞增生、星形胶质细胞增生和行为障碍的影响。两种药物在损伤后5 h单次静脉给药（0.5 mg/kg），以便比较疗效。在伤后24小时和7天，POM和DP显著减少挫伤体积。这两种药物在TBI后7天改善了短期记忆缺陷和焦虑行为。POM和DP可减少TBI后海马CA 1和齿状回（DG）区域的退化神经元数量。DP，而不是Pom，显着减弱TBI诱导的小胶质细胞增生，DP比Pom更有效地减弱TBI诱导的星形胶质细胞增生在CA 1和DG在TBI后7 D。总之，TBI后5 h单次静脉注射Pom或DP显著降低了海马神经变性并预防了认知缺陷，同时减轻了海马中的神经炎症。
Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6′-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.
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影响因子：
4.3
作者：
Jung YJ;Tweedie D;Scerba MT;Kim DS;Palmas MF;Pisanu A;Carta AR;Greig NH
通讯作者：
Greig NH
影响因子：
6.1
作者：
Chen, Szu-Fu;Hung, Tai-Ho;Wang, Jia-Yi
通讯作者：
Wang, Jia-Yi
DOI：
10.1093/brain/awaa321
发表时间：
2021-02-12
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Jamjoom AAB;Rhodes J;Andrews PJD;Grant SGN
通讯作者：
Grant SGN
影响因子：
4.2
作者：
Gao, Xiang;Deng-Bryant, Ying;Cho, Wongil;Carrico, Kimberly M.;Hall, Edward D.;Chen, Jinhui
通讯作者：
Chen, Jinhui
影响因子：
11
作者：
Hopperton KE;Mohammad D;Trépanier MO;Giuliano V;Bazinet RP
通讯作者：
Bazinet RP