Subarachnoid Hemorrhage Promotes Proliferation, Differentiation, and Migration of Neural Stem Cells via BDNF Upregulation

被引:43
作者
Lee, Wen-Di [1 ]
Wang, Kuo-Chuan [2 ,3 ]
Tsai, Yi-Fen [2 ,3 ]
Chou, Pin-Chun [1 ]
Tsai, Li-Kai [3 ,4 ,5 ]
Chien, Chung-Liang [1 ]
机构
[1] Natl Taiwan Univ, Grad Inst Anat & Cell Biol, Coll Med, Taipei, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Surg, Taipei, Taiwan
[3] Natl Taiwan Univ, Coll Med, Taipei, Taiwan
[4] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan
[5] Natl Taiwan Univ Hosp, Stroke Ctr, Taipei, Taiwan
关键词
NEUROTROPHIC FACTOR; SUBVENTRICULAR ZONE; ADULT NEUROGENESIS; NITRIC-OXIDE; BRAIN; MICROGLIA; NEURONS; SVZ; INFLAMMATION; REPLACEMENT;
D O I
10.1371/journal.pone.0165460
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Patients who suffer from subarachnoid hemorrhage (SAH) usually have long-term neurological impairments. Endogenous neurogenesis might play a potential role in functional recovery after SAH; however, the underlying neurogenesis mechanism is still unclear. We assessed the extent of neurogenesis in the subventricular zone (SVZ) to better understand the neurogenesis mechanism after SAH. We performed a rat model of SAH to examine the extent of neurogenesis in the SVZ and assessed functional effects of the neurotrophic factors in the cerebrospinal fluid (CSF) on neural stem cells (NSCs) after SAH. In this study, the proliferation, differentiation, and migratory capacities of NSCs in the SVZ were significantly increased on days 5 and 7 post SAH. Furthermore, treatment of cultured rat fetal NSCs with the CSF collected from rats on days 5 and 7 post SAH enhanced their proliferation, differentiation, and migration. Enzyme-linked immunosorbent assay (ELISA) of the CSF detected a marked increase in the concentration of brain-derived neurotrophic factor (BDNF). Treating the cultured NSCs with recombinant BDNF (at the same concentration as that in the CSF) or with CSF from SAH rats, directly, stimulated proliferation, differentiation, and migration to a similar extent. BDNF expression was upregulated in the SVZ of rats on days 5 and 7 post SAH, and BDNF release occurred from NSCs, astrocytes, and microglia in the SVZ. These results indicate that SAH triggers the expression of BDNF, which promotes the proliferation, differentiation, and migration of NSCs in the SVZ after SAH.
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页数:20
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