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KMID : 0858420090110030136
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Korean Journal of Stroke
2009 Volume.11 No. 3 p.136 ~ p.142
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Synergistic Effect of Combined Treatment with Atorvastatin and Sildenafil on Synaptogenesis and Functional Recovery after Stroke in Rats
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Kim Hahn-Young
Kang Kyoung-Ah
Kim Youn-Jung
Choi Dong-Hee
Mohammad Rakibul Hasan
Cho Hyun-Ji
Lee Jong-Min
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Abstract
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Background: Atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and sildenafil, phos-phodiesterase type-5 inhibitor, have been shown to decrease infarct size and enhance functional recovery in experimental cerebral ischemia model. We investigated that combined treatment with sildenafil and atorvastatin could synergistically promote synaptogenesis and functional recovery following focal ischemic stroke in rats.
Methods: Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min and were divided into 4 groups; control (C), atorvastatin (A), sildenafil (S), atorvastatin+sildenafil (A+S) treatment groups. The rats received subcutaneous injection of saline, atorvastatin (10 mg/kg), sildenafil (10 mg/kg) or both, daily for 5 days starting at 24 hours after MCAO. On day 2, 7 and 14, behavioral tests for motor function recovery (open field test and adhesive removal test) were performed. Infract vol-umes were measured, and western blotting for synaptophysin, growth associated protein (GAP)-43 and postsynaptic density (PSD)-95 was performed to investigate synaptogenesis.
Results: The infarct volume was reduced in A, S, and A+S groups when compared with that of C group (88.0¡¾29.2 mm3 in C, 58.7¡¾11.4 mm3 in A, 50.7¡¾8.0 mm3 in S, and 40.6¡¾7.4 mm3 in A+S, P<0.05). A+S group showed significant improvement of motor function in adhesive removal test when compared with that of C group (P<0.05). A+S group showed the trend for improvement of motor function than A or S group, how-ever it did not reach statistical significance. Immunoreactivities of synaptophysin, GAP-43 and PSD-95 were significantly increased in A+S group.
Conclusion: Combined treatment with atorvastatin and sildenfil in a rat model of focal cerebral ischemia has a synergistic effect on synaptogenesis. However, this synergistic effect is not so evident on functional recovery.
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KEYWORD
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Focal cerebral ischemia, Atorvastatin, Sildenafil, Synaptogenesis,
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