Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats.
OBJECTIVE
The study aim was to assess the effects of magnesium sulfate (MgSO(4)) 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. MgSO(4) 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, MgSO(4) 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 MgSO(4) 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, MgSO(4) did not significantly influence infarct size but reduced motor deficits, supporting its potential utility for the treatment of lacunar infarct.
Lecrux
Clotilde
C
7TMRI Facility, Division of Clinical Neuroscience, University of Glasgow, Garscube Estate, Glasgow G61 1QH, UK.
McCabe
Christopher
C
Weir
Christopher J
CJ
Gallagher
Lindsay
L
Mullin
Jim
J
Touzani
Omar
O
Muir
Keith W
KW
Lees
Kennedy R
KR
Macrae
I Mhairi
IM
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D020520:Brain Infarction / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D002545:Brain Ischemia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D019332:Endothelin-1; D006973:Hypertension / Q000150:complications*; D020772:Internal Capsule / Q000187:drug effects* / Q000473:pathology; D008274:Magnesium / Q000097:blood; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D019332:Endothelin-1; D008278:Magnesium Sulfate; D008274:Magnesium