C. Lecrux, C. McCabe, C. J. Weir, L. Gallagher, J. Mullin, O. Touzani, K. W. Muir, K. R. Lees, I. M. Macrae



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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 mm(3); interquartile range, 1.3 to 3.8, vs 1.6 mm(3) and 1.2 to 2.1, for the vehicle-treated group; by histology: 0.3 mm(3) and 0.2 to 0.9 vs 0.3 mm(3) 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.