L-serine treatment may improve neurorestoration of rats after permanent focal cerebral ischemia potentially through improvement of neurorepair.
L-serine treatment may improve neurorestoration of rats after permanent focal cerebral ischemia potentially through improvement of neurorepair.
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DOI：
10.1371/journal.pone.0093405
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Xu LH
中科院分区：
文献类型：
--
作者：
Sun L;Qiang R;Yang Y;Jiang ZL;Wang GH;Zhao GW;Ren TJ;Jiang R;Xu LH
本研究旨在探讨L丝氨酸对大鼠大脑中动脉永久性闭塞(PMCAO)后脑修复和神经功能恢复的影响。术后测定神经功能、脑损伤体积和皮质损伤情况。检测GDNF、NGF、NCAML1、Tenascin-C和Nogo-A水平。观察皮质缺血边界区神经干细胞(NSCs)的增殖分化及微血管的增殖情况。L-丝氨酸(168 mg/kg体重，ip)从pMCAO后3h开始，每隔12h重复一次，持续7d或直至实验结束。L-丝氨酸治疗：1)减少损伤体积和神经元丢失；2)促进神经功能恢复；3)上调神经生长相关因子的表达；4)促进pMCAO后内源性神经干细胞和微血管的增殖，增加新生神经元的数量。5)丝氨酸羟甲基转移酶抑制剂D-环丝氨酸拮抗L-丝氨酸对神经干细胞增殖、分化和微血管增殖的影响。结论：L-丝氨酸治疗pMCAO大鼠可减轻脑损伤，促进神经修复，其机制可能与促进神经干细胞和微血管的增殖，重建神经血管单位，促进神经修复有关。L-丝氨酸对内源性神经干细胞增殖和微血管增殖的影响部分是通过L-丝氨酸作为底物产生嘌呤和嘧啶合成所需的一碳基团以及调节某些神经生长相关因子的表达而实现的。
The present study was conducted to clarify whether treatment with L-serine can improve the brain repair and neurorestoration of rats after permanent middle cerebral artery occlusion (pMCAO). After pMCAO, the neurological functions, brain lesion volume, and cortical injury were determined. GDNF, NGF, NCAM L1, tenascin-C, and Nogo-A levels were measured. Proliferation and differentiation of the neural stem cells (NSCs) and proliferation of the microvessels in the ischemic boundary zone of the cortex were evaluated. Treatment with L-serine (168 mg/kg body weight, i.p.) began 3 h after pMCAO and was repeated every 12 h for 7 days or until the end of the experiment. L-Serine treatment: 1) reduced the lesion volume and neuronal loss; 2) improved the recovery of neurological functions; 3) elevated the expression of nerve growth-related factors; and 4) facilitated the proliferation of endogenous NSCs and microvessels activated after pMCAO and increased the number of new-born neurons. 5) D-cycloserine, an inhibitor of serine hydroxymethyltransferase, blunted the effects of L-serine on NSC proliferation, differentiation, microvascular proliferation. In conclusions, L-serine treatment in pMCAO rats can reduce brain injury and facilitate neurorestoration which is partly associated with the improvement of proliferation of NSCs and microvessels, reconstruction of neurovascular units and resultant neurorepair. The effects of L-serine on endogenous NSC proliferation and microvascular proliferation are partly mediated by the action of L-serine as a substrate for the production of one-carbon groups used for purine and pyrimidine synthesis and modulation of the expression of some nerve growth-related factors.
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影响因子：
3.7
作者：
Cui YF;Xu JC;Hargus G;Jakovcevski I;Schachner M;Bernreuther C
通讯作者：
Bernreuther C
影响因子：
5.3
作者：
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通讯作者：
Fawcett, James W.
影响因子：
3.4
作者：
Kameda, M.;Shingo, T.;Date, I.
通讯作者：
Date, I.
影响因子：
3.7
作者：
He X;Knepper M;Ding C;Li J;Castro S;Siddiqui M;Schachner M
通讯作者：
Schachner M
影响因子：
4.8
作者：
de Koning, TJ;Klomp, LWJ
通讯作者：
Klomp, LWJ