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 ∼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.