1. ¹Centre d'Imagerie-Neurosciences et Applications aux PathologieS (CI-NAPS), UMR 6232, Université de Caen Basse-Normandie, Université Paris Descartes, CNRS, CEA, CERVOxy group, Hypoxia and Cerebrovascular Pathophysiology, Centre Cyceron, Bd Henri Becquerel, CAEN Cedex, France
2. ²Porsolt and Partners Pharmacology, Z.A. des Suhards, Le Genest Saint Isle, France
3. ³Groupe Mémoire et Plasticité Comportementale (GMPc), UFR des Sciences Pharmaceutiques, Université de Caen Basse-Normandie, 5 rue Vaubénard, Caen, France

Correspondence: Dr M Bernaudin, Centre d'Imagerie-Neurosciences et Applications aux PathologieS (CI-NAPS), UMR 6232, CERVOxy, Centre Cyceron, Bd Henri Becquerel, BP5229, CAEN Cedex 14074, France. E-mail: bernaudin@cyceron.fr

Received 13 February 2008; Revised 28 March 2008; Accepted 7 April 2008; Published online 14 May 2008.

Abstract

Many studies showed beneficial effects of either erythropoietin (EPO) or mesenchymal stem cells (MSCs) treatment in cerebral ischemia. In addition to a neuroprotective role, not only EPO but also MSC favors neurogenesis and functional recovery. In an attempt to further improve postischemic tissue repair, we investigated the effect of a systemic administration of MSC, in the presence or not of EPO, on neurogenesis and functional recovery in a transient focal cerebral ischemia model in the adult rat. Twenty-four hours after ischemia, the rats were divided into four groups, namely vehicle, MSC, EPO, and MSC+EPO, and received a single intravenous injection of MSC (2 10⁶ cells) and/or a repeated intraperitoneal administration of EPO (1,000 UI/kg) for 3 days. The lesion volume, the MSC outcome, neurogenesis, and functional recovery were assessed 51 days after ischemia. The results showed that cellular proliferation and neurogenesis were increased along the lateral ventricle wall in the MSC+EPO group, whereas no significant effect was observed in groups receiving MSC or EPO alone. This effect was accompanied by an improvement of mnesic performances. Mesenchymal stem cells expressing neuronal or glial markers were detected in the ischemic hemisphere. These results suggest that EPO could act in a synergistic way with MSC to potentiate the postischemic neurogenesis.