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(Stroke. 2007;38:632.)
© 2007 American Heart Association, Inc.

Inflammation and Stroke: Introduction

Use of a Poly(ADP-Ribose) Polymerase Inhibitor to Suppress Inflammation and Neuronal Death After Cerebral Ischemia-Reperfusion

Aaron M. Hamby, BS; Sang Won Suh, MD, PhD; Tiina M. Kauppinen, PhD Raymond A. Swanson, MD

From the Department of Neurology, University of California, San Francisco, and Veterans Affairs Medical Center, San Francisco, California.

Correspondence to Raymond A. Swanson, MD, (127) Neurology, VAMC, 4150 Clement St. San Francisco, CA 94121. E-mail raymond. swanson{at}ucsf.edu

Abstract

Background and Purpose— Most stroke patients do not present for medical treatment until several hours after onset of brain ischemia. Consequently, neuroprotective strategies are required with comparably long therapeutic windows. Poly(ADP-ribose) polymerase inhibitors such as PJ34 are known to suppress microglial activation, a postischemic event that may contribute to neuronal death. We evaluated the effects of PJ34 administered 8 hours after transient forebrain ischemia.

Methods— Rats were subjected to 10 minutes of forebrain ischemia and treated with PJ34 for 7 days beginning 8 hours after reperfusion. Activated microglia and infiltrating macrophages were evaluated at serial time points between zero and 14 days after ischemia by immunostaining for CD11b. CA1 neuronal survival was evaluated 7 days after ischemia.

Results— Rats treated with PJ34 showed a near-complete inhibition of microglia/macrophage activation (evaluated on day 5) and an 84% reduction in CA1 neuronal death.

Conclusions— Administration of PJ34 as late as 8 hours after transient ischemia–reperfusion has a large protective effect on CA1 survival. This effect may be mediated by suppression of the postischemic brain inflammatory response.

Key Words: inflammation • ischemia • microglia