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

David F. Antezana, Richard E. Clatterbuck, Nabil Alkayed, Stephanie J. Murphy, Lauren G. Anderson, James Frazier, Patricia D. Hurn, Richard J. Traystman, Rafael J. Tamargo

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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°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.

Original languageEnglish (US)
Pages (from-to)860-866
Number of pages7
JournalJournal of Neurosurgery
Volume98
Issue number4
StatePublished - Apr 1 2003
Externally publishedYes

Fingerprint

Corpus Striatum
Ibuprofen
Middle Cerebral Artery Infarction
Intercellular Adhesion Molecule-1
Cerebrovascular Circulation
Hypothermia
Neurosurgical Procedures
Maximum Tolerated Dose
Caudate Nucleus
Putamen
Brain Ischemia
Autoradiography
Cell Communication
Reperfusion
Leukocytes
Anti-Inflammatory Agents
Blood Platelets
Ischemia
Endothelial Cells
Staining and Labeling

Keywords

  • Cerebral ischemia
  • Hypothermia
  • Ibuprofen
  • Intercellular adhesion molecule-1
  • Rat
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Antezana, D. F., Clatterbuck, R. E., Alkayed, N., Murphy, S. J., Anderson, L. G., Frazier, J., ... Tamargo, R. J. (2003). High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats. Journal of Neurosurgery, 98(4), 860-866.

High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats. / Antezana, David F.; Clatterbuck, Richard E.; Alkayed, Nabil; Murphy, Stephanie J.; Anderson, Lauren G.; Frazier, James; Hurn, Patricia D.; Traystman, Richard J.; Tamargo, Rafael J.

In: Journal of Neurosurgery, Vol. 98, No. 4, 01.04.2003, p. 860-866.

Research output: Contribution to journalArticle

Antezana, DF, Clatterbuck, RE, Alkayed, N, Murphy, SJ, Anderson, LG, Frazier, J, Hurn, PD, Traystman, RJ & Tamargo, RJ 2003, 'High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats', Journal of Neurosurgery, vol. 98, no. 4, pp. 860-866.
Antezana DF, Clatterbuck RE, Alkayed N, Murphy SJ, Anderson LG, Frazier J et al. High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats. Journal of Neurosurgery. 2003 Apr 1;98(4):860-866.
Antezana, David F. ; Clatterbuck, Richard E. ; Alkayed, Nabil ; Murphy, Stephanie J. ; Anderson, Lauren G. ; Frazier, James ; Hurn, Patricia D. ; Traystman, Richard J. ; Tamargo, Rafael J. / High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats. In: Journal of Neurosurgery. 2003 ; Vol. 98, No. 4. pp. 860-866.
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abstract = "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°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.",
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AU - Antezana, David F.

AU - Clatterbuck, Richard E.

AU - Alkayed, Nabil

AU - Murphy, Stephanie J.

AU - Anderson, Lauren G.

AU - Frazier, James

AU - Hurn, Patricia D.

AU - Traystman, Richard J.

AU - Tamargo, Rafael J.

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N2 - 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°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.

AB - 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°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.

KW - Cerebral ischemia

KW - Hypothermia

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KW - Intercellular adhesion molecule-1

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KW - Stroke

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