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(Stroke. 2007;38:774.)
© 2007 American Heart Association, Inc.

Adaptive Immunity: Introduction

A Novel Immune-Based Therapy for Stroke Induces Neuroprotection and Supports Neurogenesis

Yaniv Ziv, MSc; Arseny Finkelstein, BSc; Yona Geffen, PhD; Jonathan Kipnis, PhD; Igor Smirnov, MDV; Suzi Shpilman, MSc; Irena Vertkin, MSc; Michal Kimron, MSc; Aya Lange, MSc; Torsten Hecht, PhD; Klaus G. Reyman, PhD; Jonathan B. Marder, PhD; Michal Schwartz, PhD Eti Yoles, PhD

From the Department of Neurobiology (Y.Z., A.F., J.K., M.S.), The Weizmann Institute of Science, Rehovot, Israel; Proneuron Biotechnologies (Y.G., I.S., S.S., I.V., M.K., A.L., J.B.M., E.Y.), Weizmann Science Park, Ness-Ziona, Israel; and the Leibniz Institute for Neurobiology (T.H., K.G.R.), Magdeburg, Germany.

Correspondence to Eti Yoles, PhD, Proneuron Biotechnologies, Weizmann Science Park, Bldg 14, PO box 277, 74101 Ness-Ziona, Israel. E-mail eti.yoles{at}proneuron.com; or Michal Schwartz, PhD, Department of Neurobiology, The Weizmann Institute of Science, PO box 26, 76100 Rehovot, Israel. E-mail michal.Schwartz@weizmann.ac.il

Abstract

The ability of the central nervous system to cope with stressful conditions was shown to be dependent on proper T-cell–mediated immune response. Because the therapeutic window for neuroprotection after acute insults such as stroke is relatively narrow, we searched for a procedure that would allow the relevant T cells to be recruited rapidly. Permanent middle cerebral artery occlusion was induced in adult rats. To facilitate a rapid poststroke T cell activity, rats were treated with poly-YE using different regimens. Control and poly-YE–treated rats were assessed for functional recovery using neurological severity score and Morris water maze. Neuroprotection, neurogenesis, growth factor expression, and microglial phenotype were assessed using histological and immunofluorescence methods. Administration of poly-YE as late as 24 hours after middle cerebral artery occlusion yielded a beneficial effect manifested by better neurological performance, reduced neuronal loss, attenuation of behavioral deficits, and increased hippocampal and cortical neurogenesis. This compound affected the subacute phase by modulating microglial response and by increasing local production of insulin-like growth factor-I, known to be a key player in neuronal survival and neurogenesis. The relative wide therapeutic window, coupled with its efficacy in attenuating further degeneration and enhancing restoration, makes poly-YE a promising immune-based candidate for stroke therapy.

Key Words: neuroprotection • neurogenesis • reactive microglia • stroke

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