Stem Cell Therapy for HIE

描述（由申请人提供）：缺氧缺血性脑病（HIE）是全身性窒息的脑部表现，发生率为20/1000。25%的新生儿患有缺氧缺血性脑病表现出严重的永久性神经心理障碍，表现为脑瘫，伴有或不伴有相关的智力迟钝、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触发的事件级联。在实验室中，这些疗法在缺氧缺血性损伤之前或之后给予时，在限制神经元损伤方面显示出混合的结果。这些疗法在临床环境中取得的成功甚至更有限，临床医生的主要手段仍然是支持性治疗。干细胞治疗为新生儿缺氧缺血性脑病的治疗提供了一种有吸引力的方法。用功能性细胞替换坏死细胞的能力将潜在地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，因为发育中的大脑脑室下区的细胞持续分裂。这种分裂基本上为植入的干细胞迁移和分化留下了完整的化学和细胞标志。基于发育中大脑的可育环境，我们假设在缺氧缺血性脑损伤后将干细胞植入新生小鼠幼仔的脑室中将迁移到损伤区域并分化。将通过使用HIE小鼠模型来检验所提出的假设。损伤后，在损伤后24小时和7天，将干细胞植入损伤动物的侧脑室或损伤皮质中。然后在移植后7-14天收集大脑。将分析移植的干细胞的位置、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性。缺氧缺血性脑病（Hypoxic-Ischemic Encephalopathy，HIE）是新生儿全身性窒息的脑部表现，每1000名新生儿中有20例发生。25%的新生儿患有缺氧缺血性脑病表现出严重的永久性神经心理障碍，表现为脑瘫，伴有或不伴有相关的智力迟钝、学习障碍或癫痫。本研究以新生儿缺氧缺血性脑病为研究对象，探索干细胞移植治疗新生儿缺氧缺血性脑病的可行性。

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.