Authors: D Belen Ö Besalti K Yiğitkanlı K Kösemehmetoğlu S Şimşek H Bolay
Publish Date: 2007/09/17
Volume: 149, Issue: 10, Pages: 1041-1048
Abstract
Background Though cerebral vasospasm is one of the most serious complications of subarachnoid haemorrhage SAH its complex pathogenesis is poorly understood and available clinical treatment options are unsatisfactory This study was designed to examine the efficacy of leflunomide an immunomodulatory agent with inhibitory properties on vascular smooth muscle cell proliferation and inflammation in a rabbit cerebral vasospasm modelMethods Twentytwo adult NewZealand rabbits were assigned to 4 groups control SAH SAH plus vehicle SAH plus leflunomide Subarachnoid haemorrhage was induced by administration of 1 ml of fresh unheparinised autologous arterial blood into the cisterna magna Oral leflunomide 2 mg/kg or vehicle treatment was started 12 h after the induction of subarachnoid haemorrhage and administered once a day Three days later the animals were sacrificed and the basilar artery was examined histologically for the lumen area and the thickness of the vessel wall Inflammatory reaction was also examined by counting white blood cells within the vessel wall by means of light microscopic examination using haematoxylin and eosin stainingFindings Severe and moderate vasospasms were detected in the basilar artery of the SAH and SAH plus vehicle treated groups respectively Leflunomide effectively reduced the vasospasm of the basilar artery Compared to the vehicle treated group leflunomide significantly reduced the lumen area p 001 and hyperplasia of the vessel wall p 001 Although inflammatory response within the vessel wall was reduced in the leflunomide treated group no statistical significance was found between groups p = 007Conclusion This study demonstrates for the first time that leflunomide treatment attenuates cerebral vasospasm in a rabbit SAH model while inflammatory reaction in the vessel wall is not affected Although further studies are needed to reveal its molecular mechanisms in relieving vasospasm leflunomide may provide a therapeutic potential for human cerebral vasospasm induced by SAH
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