Sun Xiaoyu, Zhou Zhike, Liu Tingting, Zhao Mei, Zhao Shanshan, Xiao Ting, Jolkkonen Jukka, Zhao Chuansheng
Neurology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, Liaoning, 110001, China.
Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
J Mol Neurosci. 2016 Feb;58(2):233-42. doi: 10.1007/s12031-015-0662-y. Epub 2015 Oct 16.
Age is associated with poor outcome and impaired functional recovery after stroke. Fluoxetine, which is widely used in clinical practice, can regulate hippocampal neurogenesis in young rodents. As the rate of neurogenesis is dramatically reduced during aging, we studied the effect of post-stroke fluoxetine treatment on neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of dentate gyrus (DG) and whether this would be associated with any behavioral recovery after the cortical infarct in aged rats. Aged rats were randomly assigned to four groups: sham-operated rats, sham-operated rats treated with fluoxetine, rats subjected to cerebral ischemia, and rats with ischemia treated with fluoxetine. Focal cortical ischemia was induced by intracranial injection of vasoconstrictive peptide, endothelin-1 (ET-1). Fluoxetine was administered in the drinking water for 3 weeks starting 1 week after ischemia at a dose of 18 mg/kg/day. Behavioral recovery was evaluated on post-stroke days 29 to 31 after which the survival rate and fate of proliferating cells in the SVZ and DG were assessed by immunohistochemistry. Apoptosis was measured with the TUNEL assay. The results indicated that chronic fluoxetine treatment after stroke enhanced the proliferation of newborn neurons in the SVZ, but not in SGZ, and it suppressed perilesional apoptosis. Fluoxetine treatment did not affect the survival or differentiation of newly generated cells in the SVZ i.e., the enhanced neurogenesis was not translated into a behavioral outcome.
年龄与中风后不良预后及功能恢复受损有关。氟西汀在临床实践中广泛应用，可调节幼年啮齿动物的海马神经发生。由于衰老过程中神经发生速率显著降低，我们研究了中风后氟西汀治疗对老年大鼠齿状回（DG）室下区（SVZ）和颗粒下区（SGZ）神经发生的影响，以及这是否与皮质梗死后的行为恢复相关。老年大鼠被随机分为四组：假手术大鼠、接受氟西汀治疗的假手术大鼠、脑缺血大鼠和接受氟西汀治疗的缺血大鼠。通过颅内注射血管收缩肽内皮素-1（ET-1）诱导局灶性皮质缺血。缺血1周后开始在饮用水中给予氟西汀，剂量为18mg/kg/天，持续3周。在中风后第29至31天评估行为恢复情况，之后通过免疫组织化学评估SVZ和DG中增殖细胞的存活率和命运。用TUNEL法检测细胞凋亡。结果表明，中风后慢性氟西汀治疗可增强SVZ中新生神经元的增殖，但对SGZ无此作用，且可抑制病灶周围的细胞凋亡。氟西汀治疗不影响SVZ中新生成细胞的存活或分化，即增强的神经发生并未转化为行为结果。
