Systemic administration of mesenchymal stem cells increases neuron survival after global cerebral ischemia in vivo (2VO)

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.

Figure 1

Microphotographs (20x) of pyramidal neurons in the CA1 region of the hippocampus. Sections from (a) sham-operated rat, (b) ischemic untreated, and (c) ischemic MSC-treated rat. Shrunken neurons are indicated by arrows. Images were obtained 5 days after ischemia.

Figure 2

Number of vital neurons after ischemia in the various groups. Bars show mean and standard deviation. Probability values are for one-way analysis of variance (ANOVA) and for post hoc Bonferroni's Multiple Comparison Test.