Sonic hedgehog agonist fails to induce neural stem cell precursors in a porcine model of experimental intracranial hemorrhage.

Abstract

BACKGROUND: The role of endogenous neural stem cell progenitors in recovery from intracranial hemorrhage remains to be elucidated. Proliferation of such stem cells in the subventricular zone has been described in rodent models of experimental intracranial hemorrhage. Administration of a sonic hedgehog agonist at the time of hemorrhage was hypothesized to increase the quantity of such precursor cells. METHODS: Two groups of pigs were subjected to injection of autologous blood into the right frontal lobe. One group was also injected at the same site with a sonic hedgehog agonist at the time of the hemorrhage to stimulate cell growth, and the other was given a vehicle control. The pigs received intravenous BrdU for 5 days postoperatively to label replicating cells, and then were sacrificed at intervals up to 21 days. RESULTS: Pigs in the hemorrhage only group demonstrated increased and more persistent BrdU staining in the subventricular zone relative to pigs in the group that received sonic hedgehog agonist. The latter group demonstrated increased BrdU activity in non-neural lineage cells in the area of the hemorrhage. CONCLUSION: Sonic hedgehog agonist did not induce subventricular zone neural stem cell progenitor division after experimental intracranial hemorrhage in a pig model.