Lin Ting-Chun, Tsai Yi-Chieh, Chen Yun-An, Young Tai-Horng, Wu Chung-Che, Chiang Yung-Hsiao, Kao Chia-Hsin, Huang Abel Po-Hao, Hsu Yi-Hua, Chen Kai-Yun, Tsai Li-Kai
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Neurology and Stroke Center, National Taiwan University Hospital, Taipei, Taiwan.
Front Cell Neurosci. 2023 May 11;17:1170251. doi: 10.3389/fncel.2023.1170251. eCollection 2023.
Intracerebral hemorrhage (ICH) enhances neurogenesis in the subventricular zone (SVZ); however, the mechanism is not fully understood. We investigated the role of brain-derived neurotrophic factor (BDNF) in post-ICH neurogenesis in a rodent model and in patients with ICH using cerebrospinal fluid (CSF).
A rat model of ICH was constructed via stereotaxic injection of collagenase into the left striatum. Patients with ICH receiving an external ventricular drain were prospectively enrolled. CSF was collected from rats and patients at different post-ICH times. Primary cultured rat neural stem cells (NSCs) were treated with CSF with or without BDNF-neutralized antibody. Immunohistochemistry and immunocytochemistry were used to detect NSC proliferation and differentiation. The BDNF concentration in CSF was quantified using enzyme-linked immunosorbent assays (ELISA).
In the rat model of ICH, the percentage of proliferating NSCs and neuroblasts in SVZ was elevated in bilateral hemispheres. The cultured rat NSCs treated with CSF from both rats and patients showed an increased capacity for proliferation and differentiation toward neuroblasts. BDNF concentration was higher in CSF collected from rats and patients with ICH than in controls. Blocking BDNF decreased the above-noted promotion of proliferation and differentiation of cultured NSCs by CSF treatment. In patients with ICH, the BDNF concentration in CSF and the neurogenesis-promoting capacity of post-ICH CSF correlated positively with ICH volume.
BDNF in CSF contributes to post-ICH neurogenesis, including NSC proliferation and differentiation toward neuroblasts in a rat model and patients with ICH.
脑出血（ICH）可增强脑室下区（SVZ）的神经发生；然而，其机制尚未完全明确。我们使用脑脊液（CSF），在啮齿动物模型和ICH患者中研究了脑源性神经营养因子（BDNF）在ICH后神经发生中的作用。
通过立体定向向左侧纹状体注射胶原酶构建大鼠ICH模型。前瞻性纳入接受脑室外引流的ICH患者。在ICH后的不同时间点收集大鼠和患者的脑脊液。用有无BDNF中和抗体的脑脊液处理原代培养的大鼠神经干细胞（NSCs）。采用免疫组织化学和免疫细胞化学检测NSC的增殖和分化。使用酶联免疫吸附测定（ELISA）定量测定脑脊液中BDNF的浓度。
在大鼠ICH模型中，双侧半球SVZ中增殖的NSCs和成神经细胞的百分比均升高。用大鼠和患者的脑脊液处理的培养大鼠NSCs表现出增殖能力增强和成神经细胞分化能力增强。ICH大鼠和患者脑脊液中BDNF浓度高于对照组。阻断BDNF可降低脑脊液处理对培养NSCs增殖和分化的上述促进作用。在ICH患者中，脑脊液中BDNF浓度和ICH后脑脊液促进神经发生的能力与ICH体积呈正相关。
脑脊液中的BDNF有助于ICH后的神经发生，包括大鼠模型和ICH患者中NSC的增殖和成神经细胞分化。
