Development of cerebral ischemic model in immune deficiency mouse

血栓闭塞性脑血管疾病导致中风和永久性神经元丧失是发病率和死亡率的重要原因。由于脑血管系统的独特特性和神经元组织有限的修复能力，设计有效的脑缺血神经保护治疗一直是一个难题。我们建立了脑缺血模型。该模型重现性好，可存活12周以上。利用该模型，我们证明了在中风免疫功能受损小鼠48小时前系统给予人脐带血来源的CD34阳性细胞可诱导缺血区新生血管，并为神经元再生提供了有利的环境。内源性神经发生在抗血管生成药物的抑制下，由于神经元祖细胞向损伤区域的迁移增强，随后是它们的成熟和功能恢复，从而加速了神经发生。我们的数据表明，CD34阳性细胞在直接或间接促进有利于缺血脑新生血管形成的环境中发挥重要作用，从而使神经元再生得以进行。

Thrombo-occlusive cerebrovascular disease resulting in stroke and permanent neuronal loss is an important cause of morbidity and mortality. Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. We developed the cerebral ischemic model. The model is highly reproducible and survives for more than twelve weeks. Using this model, we demonstrated that systemic administration of human cord blood-derived CD34 positive cells to immunocompromised mice subjected to stroke 48 hours early induced neovascularization in the ischemic zone and provided a favorable environment for neuronal regeneration. Endogenous neurogenesis, suppressed by an antiangiogenic agent, is accelerated as a result of enhanced migration of neuronal progenitor cells to the damages area, followed by their maturation and functional recovery.Our data suggested an essential role for CD34 positive cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed.