Unidad de Terapia Celular, Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
Eur J Neurosci. 2018 Dec;48(12):3514-3533. doi: 10.1111/ejn.14260. Epub 2018 Dec 1.
Understanding endogenous neurogenesis and neuronal replacement to mature circuits is a topic of discussion as a therapeutic alternative under acute and chronic neurodegenerative disorders. Adaptive neurogenic response may result as a result of ischemia which could support long-term recovery of behavioral functions. Endogenous sources of neural progenitors may be stimulated by changes in blood flow or neuromodulation. Using a mouse model of unilateral cortical devascularization, we have observed reactive neurogenesis in the perilesional cortex and subventricular zone neurogenic niche. C57BL/6L 4 weeks old male mice were craneotomized at 1 mm caudal from frontal suture and 1 mm lateral from midline to generate a window of 3 mm side. Brain injury was produced by removal of the meninges and superficial vasculature of dorsal parietal cortex. BrdU agent (50 mg/kg, ip) was injected to lesioned and sham animals, during days 0 and 1 after surgery. Sagittal sections were analyzed at 1, 4, 7, and 10 days post-injury. A time-dependent increase in BrdU cells in the perilesional parietal cortex was accompanied by augmented BrdU cells in the sub ventricular and rostral migratory stream of ipsilateral and contralateral hemispheres. Neural progenitors and neuroblasts proliferated in the lesioned and non-lesioned subventricular zone and rostral migratory stream on day 4 after injury. Augmented contralateral neurogenesis was associated with an increase in vesicular monoamine transporter 2 protein in the striosomal sub ventricular neurogenic niche of non-lesioned hemisphere.
理解内源性神经发生和成熟回路中的神经元替代是急性和慢性神经退行性疾病治疗替代方案的讨论主题。缺血可能会导致适应性神经发生反应,从而支持行为功能的长期恢复。神经祖细胞的内源性来源可能会受到血流变化或神经调节的刺激。通过单侧皮质去血管化的小鼠模型,我们观察到了病变周围皮质和侧脑室下神经发生龛中的反应性神经发生。将 4 周龄雄性 C57BL/6L 小鼠在额缝后 1mm 和中线外侧 1mm 处进行颅切开术,形成 3mm 边长的窗口。通过去除背侧顶叶皮质的脑膜和浅层血管来产生脑损伤。在手术后第 0 天和第 1 天,将 BrdU 试剂(50mg/kg,ip)注射到损伤和假手术动物中。在损伤后 1、4、7 和 10 天分析矢状切片。病变周围顶叶皮质中 BrdU 细胞的时间依赖性增加伴随着同侧和对侧半球侧脑室和额迁移流中 BrdU 细胞的增加。损伤和未损伤的侧脑室下区和额迁移流中的神经祖细胞和神经母细胞在损伤后第 4 天增殖。对侧神经发生的增加与非损伤半球纹状体下脑室神经发生龛中囊泡单胺转运蛋白 2 蛋白的增加有关。