Sodium channel-blocking agents are not of benefit to rats with kaolin-induced hydrocephalus.
OBJECTIVE
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.


METHODS
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.


RESULTS
Compared with untreated hydrocephalic rats, neither mexiletine nor riluzole was associated with a protective effect on behavioral, structural, or biochemical abnormalities.


CONCLUSIONS
Protection of hydrocephalic brains through pharmacological sodium channel blockade is probably an approach not worth pursuing.
Del Bigio
Marc R
MR
Department of Pathology, University of Manitoba, and Manitoba Institute for Child Health, Winnipeg, Canada. delbigi@cc.umanitoba.ca
Wang
Xia
X
Wilson
Marla J
MJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006849:Hydrocephalus / Q000139:chemically induced / Q000188:drug therapy*; D007616:Kaolin; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000627:therapeutic use*; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D017211:Treatment Failure
D026941:Sodium Channel Blockers; D008801:Mexiletine; D007616:Kaolin; D019782:Riluzole