Development of cerebral ischemic model in immune deficiency mouse

免疫缺陷小鼠脑缺血模型的建立

• 批准号: 16590855
• 负责人: NISHIMURA Hiroyuki
• 金额: $ 1.54万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590855/
• 关键词: cerebral ischemia; angiogenesis; neurogenes; progenitor cell; neuronal function; CD34; 血管内皮前駆

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.

导致中风和永久性神经元丧失的血栓闭塞性脑血管疾病是发病和死亡的重要原因。由于脑血管系统的独特性质和神经元组织的有限修复能力，很难设计出有效的脑缺血神经保护疗法。我们开发了脑缺血模型。该模型具有高度可重复性，可保存超过十二周。使用该模型，我们证明，提前 48 小时对免疫功能低下的中风小鼠全身注射人脐带血来源的 CD34 阳性细胞，可诱导缺血区的新血管形成，并为神经元再生提供有利的环境。由于神经元祖细胞向损伤区域的迁移增强，进而促进其成熟和功能恢复，抗血管生成剂抑制的内源性神经发生加速。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部新生血管形成的环境，使神经元再生得以进行。

项目成果

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model

• DOI: 10.1172/jci200420622
• 发表时间: 2004-08-01
• 期刊: JOURNAL OF CLINICAL INVESTIGATION
• 影响因子: 15.9
• 作者: Taguchi, A;Soma, T;Matsuyama, T
• 通讯作者: Matsuyama, T