Abstract

Although many studies have shown that administration of stem cells after focal cerebral ischemia improves brain damage, very little data are available concerning the damage induced by global cerebral ischemia. The latter causes neuronal death in selectively vulnerable areas, including the hippocampal CA1 region. We tested the hypothesis that intravenous infusion of bone marrowderived stromal cells (mesenchimal stem cells, MSC) reduce brain damage after transient global ischemia. In adult male Sprague-Dawley rats transient global ischemia was induced using bilateral common carotid artery occlusion for 20 min in addition to controlled hypotension. Five days after, the animals were anaesthetized with urethane and the brain was fixed, sectioned and stained with hematoxylin-eosin to investigate histological damage. MSC did not fully protect against ischemic damage, as the number of viable neurons in this group was lower than in normal (sham-operated) rats. However, in MSC-treated rats the number of viable CA1 pyramidal neurons was significally higher than in rats that had been subjected to ischemia but not treated with MSC. We conclude that intravenous administration of MSC after transient global ischemia reduces hippocampal damage.

Highlights

  • Bone marrow (BM) contains populations of precursors that are multipotent and have the characteristics of stem cells of nonhematopoietic tissues

  • Regardless of the mechanisms of tissue protection, several data exist concerning the effects of stem cells in the experimental therapy of focal cerebral ischemia [6, 11,12,13,14], but little research has been done in global cerebral ischemia, encouraging data exist for this model, too [15]

  • The present study investigated the therapeutic potential of mesenchymal stem cells (MSCs) in a rat model of diffuse neuronal damage induced by global ischemia

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Summary

Introduction

Bone marrow (BM) contains populations of precursors that are multipotent and have the characteristics of stem cells of nonhematopoietic tissues. The precursors of nonhematopoietic tissues are referred to as bone marrow stromal cells (BMSCs) or mesenchymal stem cells (MSCs) They have attracted interest because of their capacity for selfrenewal in a number of nonhematopoietic tissues and their multipotentiality for differentiation. They are able to cross the blood-brain barrier, to migrate throughout forebrain and cerebellum, and to differentiate to some extent into astrocytes and neurons Despite their transdifferentiation potential, recent data have shown that MSCs display a significant capacity of decreasing inflammation, modulating immune responses, and protecting tissues from injuries, mostly through bystander paracrine mechanisms [1]. These cells are selectively vulnerable to global ischemic damage and can gauge the effects of such a damage [19]

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