Roscovitine reduces neuronal loss, glial activation, and neurologic deficits after brain trauma.
Roscovitine reduces neuronal loss, glial activation, and neurologic deficits after brain trauma.
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DOI：
10.1038/jcbfm.2008.75
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发表时间：
2008-11
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影响因子：
--
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中科院分区：
文献类型：
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TBI导致直接和延迟的组织损伤。后者与导致神经元死亡、炎症和神经胶质瘢痕形成的细胞周期活化等继发性生化变化有关。Flavopiridol是一种既没有特异性也没有选择性的CDK抑制剂，具有神经保护作用。为了研究更特异性的CDK抑制剂作为潜在神经保护剂的作用，我们研究了Roscovitine在TBI中的作用。损伤后30分钟的roscovitine中枢给药导致病变体积显著减小，以及运动和认知恢复改善。Roscovitine减弱神经元死亡，抑制TBI后神经元细胞周期途径的激活，如减弱的细胞周期蛋白G1积累和视网膜母细胞瘤蛋白磷酸化所示。治疗还降低了TBI后的小胶质细胞活化，如ED 1、半乳糖凝集素-3、p22 PHOX和Iba-1水平的降低所反映的，并且如GFAP积累减少所示的减弱了星形胶质细胞增生。在原代皮质小胶质细胞和神经元培养物中，roscovitine和其他选择性CDK抑制剂减弱神经元细胞死亡，以及减少小胶质细胞活化和小胶质细胞依赖性神经毒性。这些数据支持TBI后细胞周期抑制的多因素神经保护作用-可能与抑制神经元凋亡、小胶质细胞诱导的炎症和神经胶质增生相关-并表明多种CDK可能参与该过程。
TBI causes both direct and delayed tissue damage. The latter is associated with secondary biochemical changes such as cell cycle activation that lead to neuronal death, inflammation and glial scarring. Flavopiridol — a CDK inhibitor that is neither specific nor selective — is neuroprotective. To examine the role of more specific CDK inhibitors as potential neuroprotective agents, we studied the effects of roscovitine in TBI. Central administration of roscovitine 30 minutes after injury resulted in significantly decreased lesion volume, as well as improved motor and cognitive recovery. Roscovitine attenuated neuronal death and inhibited activation of cell cycle pathways in neurons after TBI, as indicated by attenuated cyclin G1 accumulation and phosphorylation of retinoblastoma protein. Treatment also decreased microglial activation after TBI, as reflected by reductions in ED1, Galectin-3, p22PHOX and Iba-1 levels, and attenuated astrogliosis as shown by decreased GFAP accumulation. In primary cortical microglia and neuronal cultures, roscovitine and other selective CDK inhibitors attenuated neuronal cell death, as well as decreasing microglial activation and microglial-dependent neurotoxicity. These data support a multi-factorial neuroprotective effect of cell cycle inhibition after TBI-likely related to inhibition of neuronal apoptosis, microglial-induced inflammation and gliosis-and suggest that multiple CDKs are potentially involved in this process.
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DOI：
10.1111/j.1432-1033.1997.t01-2-00527.x
发表时间：
1997-01-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Meijer, L;Borgne, A;Moulinoux, JP
通讯作者：
Moulinoux, JP
影响因子：
8.3
作者：
Ito, D;Tanaka, K;Fukuuchi, Y
通讯作者：
Fukuuchi, Y
DOI：
10.1097/01.wcb.0000046143.31247.fd
发表时间：
2003-03-01
影响因子：
6.3
作者：
Faden, AI;Knoblach, SM;Kozikowski, AP
通讯作者：
Kozikowski, AP
影响因子：
6.2
作者：
Lai, Aaron Y.;Todd, Kathryn G.
通讯作者：
Todd, Kathryn G.
影响因子：
5.3
作者：
Maeda, M;Ampo, KI;Kiyama, H
通讯作者：
Kiyama, H