Del Bigio Marc R, Wang Xia, Wilson Marla J
Department of Pathology, University of Manitoba, and Manitoba Institute for Child Health, Winnipeg, Canada.
Neurosurgery. 2002 Aug;51(2):460-6; discussion 466-7. doi: 10.1097/00006123-200208000-00029.
Hydrocephalus causes damage to periventricular white matter at least in part through chronic ischemia. The sodium channel-blocking agents mexiletine and riluzole have been shown to be of some protective value in various models of neurological injury. We hypothesized that these agents would ameliorate the effects of experimental childhood-onset hydrocephalus.
Hydrocephalus was induced in 4-week-old rats by injection of kaolin into the cisterna magna. Tests of cognitive and motor function were performed on a weekly basis. In a blinded and randomized manner, mexiletine (0.7, 7, or 42 mg/kg/d) or riluzole (1.4 or 13.6 mg/kg/d) was administered by osmotic minipump for 2 weeks, beginning 2 weeks after induction of hydrocephalus. The brains were then subjected to histopathological and biochemical analyses.
Compared with untreated hydrocephalic rats, neither mexiletine nor riluzole was associated with a protective effect on behavioral, structural, or biochemical abnormalities.
Protection of hydrocephalic brains through pharmacological sodium channel blockade is probably an approach not worth pursuing.
脑积水至少部分通过慢性缺血导致脑室周围白质损伤。钠通道阻滞剂美西律和利鲁唑已被证明在各种神经损伤模型中具有一定的保护作用。我们假设这些药物将改善实验性儿童期脑积水的影响。
通过向大鼠小脑延髓池注射高岭土，在4周龄大鼠中诱导脑积水。每周进行认知和运动功能测试。在脑积水诱导2周后，以盲法和随机方式通过渗透微型泵给予美西律（0.7、7或42mg/kg/天）或利鲁唑（1.4或13.6mg/kg/天），持续2周。然后对大脑进行组织病理学和生化分析。
与未治疗的脑积水大鼠相比，美西律和利鲁唑均未对行为、结构或生化异常产生保护作用。
通过药理学钠通道阻滞保护脑积水大脑可能是一种不值得追求的方法。
