Magnesium sulfate therapy is of mild benefit to young rats with kaolin-induced hydrocephalus

Hydrocephalus causes damage to periventricular white matter at least in part through chronic ischemia. Magnesium sulfate (MgSO4) has been shown to be protective in various models of neurologic injury. We hypothesized that this agent would ameliorate the effects of experimental childhood-onset hydrocephalus. Hydrocephalus was induced in 3- and 4-wk-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, MgSO4 was administered in two separate experiments (s.c. injection 0.85, 4.1, or 8.2 mM/kg/d), supplemented by osmotic minipump infusion (0.03 mM/d) to prevent low trough levels for 2 wk, beginning 2 wk after induction of hydrocephalus. The brains were then subjected to histopathological and biochemical analyses. With the 4.1 mM/kg/d dose, serum Mg++ levels were elevated transiently from 1.3 to approximately 7 mM/L. We observed statistically significant improvement in gait performance and reduced astroglial reaction. There was also a trend to improved memory performance, but no evidence of increased myelin or synaptic protein content. The 8.2 mM/kg/d dose was associated with sedation and there was no evidence of improvement in any parameter. We conclude that MgSO4 might be mildly protective in experimental hydrocephalus.