脇田 英明

Vascular dementia is a heterogeneous syndrome, and includes subcortical ischemic vascular dementia. For translational research, subcortical ischemic vascular dementia is an appropriate target since this is the most prevalent subtype and exhibits relatively uniform clinical and neuropathological changes. These changes consist of hypertensive arteriolar changes, lacunar infarctions, hypertensive hemorrhage and white matter lesions. Among various species, rodents are most frequently used, but their small volume of white matter may impede analysis of white matter lesions. Primate models have a larger volume, but the degree of white matter lesions is inconsistent. Animal models should accommodate the effect of aging and comorbidities, and in the case of primate models, low accessibility should be overcome by repeated and quantitative examinations using modern neuroimaging techniques and functional measures, especially for memory and motor function. There is no model that replicates all features of subcortical ischemic vascular dementia and, therefore, rodent and primate models should be selected appropriately for translational research. © 2014 Future Medicine Ltd.

Regenerative therapy using stem cells is a promising approach for the treatment of stroke. Recently, we reported that dental pulp stem cells (DPSC) ameliorated ischemic tissue injury in the rat brain and accelerated functional recovery after middle cerebral artery occlusion (MCAO). In this study, we investigated the effects of stem cells from human exfoliated deciduous tooth (SHED)-derived conditioned medium (SHED-CM) on permanent MCAO (pMCAO). Adult male Sprague-Dawley rats were subjected to pMCAO. SHED-CM were then administered intranasally, and the motor function and infarct volume were evaluated. Neurogenesis and vasculogenesis were determined using immunochemical markers. The SHED-CM group had more positive signals than the Dulbecco's modified Eagle's medium group, with doublecortin (DCX), neurofilament H, neuronal nuclei, and rat endothelial cell antigen observed in the peri-infarct area. Migration of neuronal progenitor cells (NPC) with DCX from the subventricular zone to the peri-infarct area was observed on days 6 and 16, with migration on day 6 being the most prominent. In conclusion, SHED-CM promoted the migration and differentiation of endogenous NPC, induced vasculogenesis, and ameliorated ischemic brain injury after pMCAO as well as transplantation of DPSC.