The mechanisms by which
mexiletine exerts its effects in increasing myocardial circulation, and smooth muscle perfusion and alleviating diabetic
neuropathic pain have been widely discussed. The purpose of this study was to examine the protective effect of this compound in
ischemia/reperfusion-induced cerebral injury following
middle cerebral artery occlusion in Sprague-Dawley rats. Blood flow to the left cerebral hemisphere of the animals was interrupted by occluding the left cerebral artery and both carotid arteries simultaneously for 3 hrs. These animals were assigned to one of ten groups and divided into treatment group and pretreatment group; 1) control treatment group (n=8); 2) vehicle treatment group (n=8); 3) lower dose
mexiletine (400 microg/kg) treatment group (n=8); 4) medium dose
mexiletine (800 microg/kg) treatment group (n=8); 5) high dose
mexiletine (2 mg/kg) treatment group (n=8); 6) control pretreatment group (n=8); 7) vehicle pretreatment group (n=8); 8) lower dose
mexiletine (400 microg/kg) pretreatment group (n=8); 9) medium dose
mexiletine (800 microg/kg) pretreatment group (n=8); and 10) high dose
mexiletine (2 mg/kg) pretreatment group (n=8). The volume of
cerebral infarction was measured in serial brain sections stained with
triphenyltetrazolium chloride (TTC). Tissue
infarction volume and tissue
edema were estimated for each animal. The volume of
cerebral infarction was significantly decreased in rats pretreated with
mexiletine, and the ratio of tissue
edema was also decreased as the dose of
mexiletine increased. These results demonstrate that
mexiletine, an
anti-arrhythmic and use-dependent Na+ channel blocker, has protective effects in
stroke at concentrations sufficient to confer significant protection, as measured by the volume of
infarction and
brain edema index in a model of focal, neocortical
ischemia in Sprague-Dawley rats.