Johnston Michael V, Hoon Alexander H
Kennedy Krieger Institute and Department of Neurology, Johns Hopkins University School of Medicine, 707 North Broadway, Baltimore, MD 21205, USA.
Neuromolecular Med. 2006;8(4):435-50. doi: 10.1385/NMM:8:4:435.
Cerebral palsy (CP) is a group of disorders of movement and posture resulting from nonprogressive disturbances of the fetal or neonatal brain. More than 80% of cases of CP in term infants originate in the prenatal period; in premature infants, both prenatal or postnatal causes contribute. The most prevalent pathological lesion seen in CP is periventricular white matter injury (PWMI) resulting from vulnerability of the immature oligodendrocytes (pre-OLs) before 32 wk of gestation. PWMI is responsible for the spastic diplegia form of CP and a spectrum of cognitive and behavioral disorders. Oxidative stress and excitotoxicity resulting from excessive stimulation of ionotropic glutamate receptors on preOLs are the most prominent molecular mechanisms for PWMI. Asphyxia around the time of birth in term infants accounts for less than 15% of CP in developed countries but the incidence is higher in underdeveloped areas. Asphyxia causes a different pattern of brain injury and CP than is seen after preterm injuries. This type of CP is associated with the clinical syndrome of hypoxic-ischemic encephalopathy shortly after the insult, and the cortex, basal ganglia, and brainstem are selectively vulnerable to injury. Experimental models indicate that neurons in the neonatal brain are more likely to die by delayed apoptosis extending over days to weeks than those in the adult brain. Neurons die by glutamate-mediated excitotoxicity involving downstream caspase-dependent and caspase-independent cell death pathways. Recent reports indicate that males and females preferentially utilize different pathways. Clinical trials indicate that mild hypothermia reduces death or disability in term infants following asphyxia and basic research suggests that this approach might be combined with pharmacological strategies in the future.
脑瘫（CP）是一组因胎儿或新生儿脑部非进行性病变而导致的运动和姿势障碍。足月儿中超过80%的脑瘫病例起源于产前阶段；早产儿的病因则包括产前和产后因素。脑瘫中最常见的病理损害是脑室周围白质损伤（PWMI），这是由于妊娠32周前未成熟少突胶质细胞（前少突胶质细胞）的脆弱性所致。PWMI是导致痉挛性双瘫型脑瘫以及一系列认知和行为障碍的原因。前少突胶质细胞上离子型谷氨酸受体过度刺激所导致的氧化应激和兴奋性毒性是PWMI最主要的分子机制。在发达国家，足月儿出生时窒息导致的脑瘫占比不到15%，但在欠发达地区发病率更高。窒息导致的脑损伤和脑瘫模式与早产损伤后不同。这种类型的脑瘫在损伤后不久与缺氧缺血性脑病的临床综合征相关，且大脑皮层、基底神经节和脑干对损伤具有选择性易感性。实验模型表明，与成人大脑相比，新生大脑中的神经元更易通过持续数天至数周的延迟凋亡而死亡。神经元通过谷氨酸介导的兴奋性毒性死亡，涉及下游半胱天冬酶依赖性和非依赖性细胞死亡途径。最近的报告表明，男性和女性优先使用不同的途径。临床试验表明，轻度低温可降低足月儿窒息后的死亡或残疾风险，基础研究表明，未来这种方法可能与药物策略相结合。
