Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats

Clotilde Lecrux, Christopher McCabe, Christopher J. Weir, Lindsay Gallagher, Jim Mullin, Omar Touzani, Keith W. Muir, Kennedy R. Lees, I. Mhairi Macrae

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Abstract

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.

Original languageEnglish
Pages (from-to)448-454
Number of pages7
JournalStroke
Volume39
Issue number2
DOIs
Publication statusPublished - 3 Jan 2008

Keywords

  • endothelin
  • lacunar infarct
  • magnesium
  • functional recovery
  • white matter
  • FOCAL CEREBRAL-ISCHEMIA
  • WHITE-MATTER INJURY
  • SPINAL-CORD-INJURY
  • CATION CHANNELS
  • NMDA RECEPTORS
  • ANIMAL-MODEL
  • SULFATE
  • STROKE
  • BRAIN
  • ENDOTHELIN-1

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