Pre- and post-treatment with cyclosporine a in a rat model of transient focal cerebral ischaemia with multimodal MRi screening
Cho, T.-H.; Aguettaz, P.; Campuzano, O.; Charriaut-Marlangue, C.; Riou, A.; Berthezène, Y.; Nighoghossian, N.; Ovize, M.; Wiart, M.èn.; Chauveau, F.
International Journal of Stroke Official Journal of the International Stroke Society 8(8): 669-674
ISSN/ISBN: 1747-4949 PMID: 22882746 DOI: 10.1111/j.1747-4949.2012.00849.x
Irreversible damage may occur at reperfusion after sustained cerebral ischaemia. We investigated the value of cyclosporine A for reducing the infarct size in a model of transient middle cerebral artery occlusion. Twenty-seven Sprague-Dawley rats sustained a middle cerebral artery occlusion of one-hour. Acute multimodal Magnetic Resonance Imaging (MRI) was used during occlusion to confirm the success of surgery and measure baseline lesion size. Animals were randomly treated by: (i) intracarotid cyclosporine A (10 mg/kg) 20 mins before middle cerebral artery occlusion (pretreatment group); (ii) intracarotid cyclosporine A (10 mg/kg) immediately after reperfusion (post-treatment group); and (iii) intracarotid saline immediately after reperfusion. Histopathological measurements on day 1 showed a significant reduction of infarct size in the pretreatment group compared to the post-treatment (percentage values of ipsilateral hemispheres: 16 ± 5% vs. 29 ± 11%, P = 0·004) and saline groups (16 ± 5% vs. 42 ± 12%, P = 0·015). No significant difference was observed between the post-treatment and saline groups (P = 0·065). Behavioural examinations on day 1 showed no significant difference between groups. Immunohistochemistry showed a statistically significant reduction of microglial cell count in the pretreatment group compared to either saline or cyclosporine A post-treatment groups. We conclude that intracarotid cyclosporine A is effective in reducing infarct size when given prior to ischaemia, but not when administered at reperfusion.