Differentiation and Angiogenesis of Central Nervous System Stem Cells Implanted with Mesenchyme into Ischemic Rat Brain

Abstract

After cerebral infarction, necrosis in neural tissues is not usually repaired or reconstructed by the injured brain. We therefore examined the effects on postinfarction repair of implanting central nervous system (CNS) stem cells together with mesenchyme, because CNS stem cells can be expected to adapt and survive in the adult brain. Cerebral infarction was induced by the Koizumi-Longa method, using the adult male spontaneous hypertensive rat model. Reperfusion was performed an hour after middle cerebral artery occlusion. The rat mesencephalic neural plate at the early somite stage (embryonic day 10.5) together with the adjacent ventral mesenchymal tissues was dissected out under the microscope and immediately implanted into the ischemic rat striatum. One month later, the cognitive function was evaluated by the Morris water maze method. Histologic and immunohistochemical examinations of the graft were made with hematoxylin-eosin (H&E), neurofilament-200, and tyrosine hydroxylase (TH) stains. In the water maze study, mean latency times required to reach an escape platform in the implanted animals with surviving grafts were found to be shorter than in those without grafts, but longer than in normal animals. In the spatial probe trial, the number of animals seen to cross the area in the pool where the platform had been located was greater in the implanted rats with surviving grafts than in other groups. Multiple vascularization in the grafted area was observed histologically in H&E-stained tissues, and neurofilament-200-positive cells were recognized in the graft. TH staining revealed within the graft many immunoreactive neuron-like cell bodies with long dendrites. It was suggested that grafted CNS stem cells with mesenchyme may survive and differentiate into mature CNS tissue within the adult ischemic rat brain, constructing vessels in and around the grafts, and may therefore have the potential to be effective in the recovery of the cognitive function of the rat model.