High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats Export

@article{antezana03high, abstract = {1: J Neurosurg. 2003 Apr;98(4):860-6.Links High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats.Antezana DF, Clatterbuck RE, Alkayed NJ, Murphy SJ, Anderson LG, Frazier J, Hurn PD, Traystman RJ, Tamargo RJ. Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland 21287, USA. OBJECT: Ibuprofen is an antiinflammatory drug that disrupts leukocyte-endothelial cell interactions by limiting expression of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), also known as CD54. The authors hypothesized that ibuprofen could reduce the size of the infarct associated with transient focal ischemia by inhibition of ICAM-1 expression, and they evaluated its effects in rats treated with middle cerebral artery (MCA) occlusion. Ibuprofen treatment was compared with mild systemic hypothermia, which is known to be neuroprotective and is commonly used during neurosurgical procedures. METHODS: The maximum ibuprofen dose (240 mg/kg/day) that could be tolerated with no systemic toxicity was established in the initial experiments. In the efficacy experiment, rats were pretreated with vehicle, ibuprofen, or hypothermia (33 degrees C) prior to 2 hours of MCA occlusion; then their brains were harvested at 24 hours of reperfusion for histological studies. End-ischemic cerebral blood flow (CBF) was evaluated using [14C]iodoantipyrine autoradiography in additional cohorts. Expression of ICAM-1 within ischemic compared with nonischemic caudate nucleus and putamen (striatum) or cortex was evaluated using immunohistochemical studies. Compared with vehicle treatment, ibuprofen produced a 46.2\% reduction (p = 0.01) in striatal infarcts, which was comparable to hypothermia (48.7\% reduction, p = 0.02). Ibuprofen did not alter end-ischemic CBF in any region studied, and the ibuprofen treatment group had the lowest proportion of animals with marked ICAM-1 staining. CONCLUSIONS: Ibuprofen given in maximum tolerated doses reduces the striatal infarct size after focal cerebral ischemia. The neuroprotective mechanism does not work through preservation of intraischemic CBF and is consistent with inhibition of ICAM-1 expression; however, at the doses used in this study, other effects of ibuprofen on platelet and endothelial function are possible.}, author = {Antezana, D. F. and Clatterbuck, R. E. and Alkayed, N. J. and Murphy, S. J. and Anderson, L. G. and Frazier, J. and Hurn, P. D. and Traystman, R. J. and Tamargo, R. J.}, citeulike-article-id = {3824654}, journal = {JOURNAL OF NEUROSURGERY}, keywords = {icam-1}, number = {4}, pages = {860--866}, posted-at = {2008-12-26 17:46:59}, priority = {2}, publisher = {WAVERLY PRESS INC}, title = {High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats}, volume = {98}, year = {2003} }

TY - JOUR ID - antezana03high L3 - citeulike-article-id:3824654 N2 - 1: J Neurosurg. 2003 Apr;98(4):860-6.Links High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats.Antezana DF, Clatterbuck RE, Alkayed NJ, Murphy SJ, Anderson LG, Frazier J, Hurn PD, Traystman RJ, Tamargo RJ. Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland 21287, USA. OBJECT: Ibuprofen is an antiinflammatory drug that disrupts leukocyte-endothelial cell interactions by limiting expression of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), also known as CD54. The authors hypothesized that ibuprofen could reduce the size of the infarct associated with transient focal ischemia by inhibition of ICAM-1 expression, and they evaluated its effects in rats treated with middle cerebral artery (MCA) occlusion. Ibuprofen treatment was compared with mild systemic hypothermia, which is known to be neuroprotective and is commonly used during neurosurgical procedures. METHODS: The maximum ibuprofen dose (240 mg/kg/day) that could be tolerated with no systemic toxicity was established in the initial experiments. In the efficacy experiment, rats were pretreated with vehicle, ibuprofen, or hypothermia (33 degrees C) prior to 2 hours of MCA occlusion; then their brains were harvested at 24 hours of reperfusion for histological studies. End-ischemic cerebral blood flow (CBF) was evaluated using [14C]iodoantipyrine autoradiography in additional cohorts. Expression of ICAM-1 within ischemic compared with nonischemic caudate nucleus and putamen (striatum) or cortex was evaluated using immunohistochemical studies. Compared with vehicle treatment, ibuprofen produced a 46.2% reduction (p = 0.01) in striatal infarcts, which was comparable to hypothermia (48.7% reduction, p = 0.02). Ibuprofen did not alter end-ischemic CBF in any region studied, and the ibuprofen treatment group had the lowest proportion of animals with marked ICAM-1 staining. CONCLUSIONS: Ibuprofen given in maximum tolerated doses reduces the striatal infarct size after focal cerebral ischemia. The neuroprotective mechanism does not work through preservation of intraischemic CBF and is consistent with inhibition of ICAM-1 expression; however, at the doses used in this study, other effects of ibuprofen on platelet and endothelial function are possible. IS - 4 JF - JOURNAL OF NEUROSURGERY EP - 866 TI - High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats PB - WAVERLY PRESS INC VL - 98 SP - 860 KW - icam-1 AU - Antezana, DF AU - Clatterbuck, RE AU - Alkayed, NJ AU - Murphy, SJ AU - Anderson, LG AU - Frazier, J AU - Hurn, PD AU - Traystman, RJ AU - Tamargo, RJ PY - 2003/// ER -