Minocycline improves cerebral edema after transient middle cerebral artery occlusion in rats

Abstract

Background: Ischemic stroke is the third leading reason for disability globally. The aim of this work was to evaluate the neuroprotective effect of minocycline following transient cerebral ischemia induced by occlusion of middle cerebral artery (MCA) in rats.
Methods: 54 male Wister rats 8 weeks old and weighted from 250 to 280 grams were categorized into three main groups each contains 18 rats: Group 1: for Gelatin zymography, Group 2: for Evan’s blue and Group 3: for behavioural assessment (n=18). Each group was divided into three subgroups (6 rats each): sham group, ischemia group: through MCA occlusion with reperfusion after one hour and Minocycline treated group: injected with a single dosage (3 mg/kg) into the left jugular vein shortly following reperfusion.
Results: Gelatine zymography test showed that after focal ischemia, matrix metalloproteinases (MMP)-9 and Pro-MMP-2 activity was upregulated compared to sham group. Minocycline treatment reduced the upregulation of MMP-9. Moreover, Minocycline treatment could significantly reduce the blood brain barrier (BBB) disruption as evidenced by the decreased Evans blue staining 1.88 (1.63-2.28) µg/g compared to ischemia group 10.81 (10.15-11.27) µg/g (p=0.023). Cerebral ischemia group showed significant decrease in rotarod 90.3 (81.6-98.13) seconds compare to in sham operated group 163.7 (160.3-165.5) seconds (P1<0.001). The treatment with Minocycline caused insignificant increase in the rotarod score 105.1 (98.03-109.7) seconds compared to ischemia group (p=0.160).
Conclusions: Minocycline has neuroprotective effects after cerebral ischemia as evidenced by reduced post-ischemic edema and inhibition of MMP-9 activity with insignificant effect on behavioural test.