文档介绍：Neonatal Neurological Diseases
陈超
Children’s Hospital,Fudan University
Neonatal Hypoxic-Ischemic Encephalopathy 新生儿缺氧缺血性脑病 (HIE)
Hypoxia
Perinatal asphyxia, apnea, respiratory failure,
right to left shunt
Ischemia
Heart arrest,Heart failure, Shock
1. Causes
Onset of HIE
Timing of Insults Percentage
Antepartum 20
Intrapartum 35
Antepartum antepartum 35
Postnatal 10
1. Cerebral hemodynamic alteration:
脑血流重分布 Initial changes:redistribution of circulation (diving reflex) cerebral blood flow↑ Continue insult:loss of vascular autoregulation, systemic hypotension, cerebral blood flow↓ cerebral ischemia
Pathogenesis
Pathogenesis (Cont’s)
2. Effects of Hypoxic-Ischemic Insults on Energy Metabolism(能力代谢)
(1) Brain glucose
(2) Lactate production
(3) ATP
(4) Energy failure
(5) Neuronal death
Pathogenesis (Cont’s)
3. Role of Free Radicals (自由基)
(1) Perioxidation (过氧化) of membrane
phospholipids
(2) Damage to DNA
(3) Activation of proapoptotic (促凋亡) genes
Pathogenesis (Cont’s)
4. Calcium Reflux(钙内流)
Activate phospholipases (磷脂酶)
Activate proteases (蛋白酶)
Activate nucleases (核酸酶)
neurotransmitter release
钙内流,导致细胞死亡
Pathogenesis (Cont’s)
5. Neurotoxicity of Excitatory Amino Acids (兴奋性氨基酸)
(1) Na+ entry: with H2O cell swelling and lysis
(2) Ca+ entry: Ca+-mediated events to cell death
Pathogenesis (Cont’s)
6. Delayed Cell Death (迟发性神经元死亡)
(1) Cell death: Necrosis (坏死) and Apoptosis (凋亡)
(2) Necrosis:occurs in minutes
(3) Apoptosis: delayed cell death occurs over hours
or days, or months