Background and Purpose—The study aim was to assess the effects of magnesium sulfate (MgSO₄) administration on white matter damage in vivo in spontaneously hypertensive rats.

Methods—The left internal capsule was lesioned by a local injection of endothelin-1 (ET-1; 200 pmol) in adult spontaneously hypertensive rats. MgSO₄ was administered (300 mg/kg SC) 30 minutes before injection of ET-1, plus 200 mg/kg every hour thereafter for 4 hours. Infarct size was measured by T2-weighted magnetic resonance imaging (day 2) and histology (day 11), and functional recovery was assessed on days 3 and 10 by the cylinder and walking-ladder tests.

Results—ET-1 application induced a small, localized lesion within the internal capsule. Despite reducing blood pressure, MgSO₄ did not significantly influence infarct volume (by magnetic resonance imaging: median, 2.1 mm³; interquartile range, 1.3 to 3.8, vs 1.6 mm³ and 1.2 to 2.1, for the vehicle-treated group; by histology: 0.3 mm³ and 0.2 to 0.9 vs 0.3 mm³ and 0.2 to 0.5, respectively). Significant forelimb and hindlimb motor deficits were evident in the vehicle-treated group as late as day 10. These impairments were significantly ameliorated by MgSO₄ in both cylinder (left forelimb use, P<0.01 and both-forelimb use, P<0.03 vs vehicle) and walking-ladder (right hindlimb score, P<0.02 vs vehicle) tests.

Conclusions—ET-1–induced internal capsule ischemia in spontaneously hypertensive rats represents a good model of lacunar infarct with small lesion size, minimal adverse effects, and a measurable motor deficit. Despite inducing mild hypotension, MgSO₄ did not significantly influence infarct size but reduced motor deficits, supporting its potential utility for the treatment of lacunar infarct.