Stem Cell Therapy for HIE

描述（由申请人提供）：缺氧缺血性脑病（HIE）是系统性窒息的脑部表现，每1000个新生儿中发生20个。25%患有HIE的新生儿表现出严重的永久性神经心理障碍，表现为脑瘫，伴有或不伴有智力迟钝、学习障碍或癫痫。由于HIE的破坏性后果，许多研究都集中在中断由HIE引发的级联事件上。在实验室中，在缺氧缺血性损伤之前或之后给予这些治疗，在限制神经元损伤方面显示出不同的结果。这些疗法在临床环境中取得了更有限的成功，临床医生的主要手段仍然是支持治疗。干细胞治疗为HIE提供了一种有吸引力的治疗方法。用功能细胞替代坏死细胞的能力可能会限制长期神经功能缺损的程度。这种疗法特别适合于新生儿，因为发育中的大脑的脑室下区细胞持续分裂。这种分裂基本上为移植干细胞的迁移和分化留下了完整的化学和细胞标志。基于发育中的大脑的肥沃环境，我们假设在缺氧缺血性脑损伤后，干细胞植入新生小鼠幼崽的脑室会迁移到损伤区域并分化。提出的假设将通过使用HIE小鼠模型进行验证。损伤后，分别于损伤后24小时和7天将干细胞植入损伤动物的侧脑室或损伤皮层。然后在移植后7-14天收集大脑。将分析移植干细胞的位置、细胞类型和分化程度。还将进行轴突示踪研究，以开始了解植入细胞的生理活动。缺氧缺血性脑病（HIE）是系统性窒息的脑部表现，每1000个新生儿中发生20个。25%患有HIE的新生儿表现出严重的永久性神经心理障碍，表现为脑瘫，伴有或不伴有智力迟钝、学习障碍或癫痫。这个项目开始探索一种潜在的治疗方法，干细胞移植，使用动物模型治疗HIE。

DESCRIPTION (provided by applicant): Hypoxic-Ischemic Encephalopathy (HIE) is the brain manifestation of systemic asphyxia which occurs in 20 out of 1000 births. 25% of neonates who suffer from HIE exhibit severe permanent neuropsychological handicaps in the form of cerebral palsy, with or without associated mental retardation, learning disabilities, or epilepsy. Due to the devastating consequences of HIE, much research has focused on interrupting the cascade of events which are triggered by HIE. In the lab, these therapies have shown mixed results in limiting neuronal injury when given before or after the hypoxic-ischemic insult. These therapies have met with even more limited success in the clinical environment and the clinician's main armamentarium still remains supportive care. Stem cell therapy offers an attractive therapy for HIE. The ability to replace necrotic cells with functional cells would potentially limit the degree of long term neurological deficits. This therapy is particularly suited to the neonate due to the continued division of cells in the subventricular zones of the developing brain. This division essentially leaves intact chemical and cellular sign posts for the implanted stem cells to migrate and differentiate. Based on the fertile milieu in the developing brain, we hypothesize that stem cells implanted into the ventricles of neonatal mouse pups following hypoxic-ischemic brain injury will migrate to the area of injury and differentiate. The proposed hypothesis will be tested by using a mouse model of HIE. Following injury, stem cells will be implanted into the injured animal in either the lateral ventricle or injured cortex at 24 hours and 7 days post injury. Brains will then be collected 7-14 days post transplant. The location, cell type, and degree of differentiation of the transplanted stem cells will be analyzed. Axonal tracing studies will also be performed to begin to understand the physiologic activity of the implanted cells. Hypoxic-Ischemic Encephalopathy (HIE) is the brain manifestation of systemic asphyxia which occurs in 20 out of 1000 births. 25% of neonates who suffer from HIE exhibit severe permanent neuropsychological handicaps in the form of cerebral palsy, with or without associated mental retardation, learning disabilities, or epilepsy. This project begins to explore a potential therapy, stem cell transplants, for HIE using an animal model.