Bone marrow-derived cell infiltration and differentiation in mouse models of Parkinson's disease and stroke

We characterized the time course and distribution of bone-marrow derived cell (BMDC) infiltration in two models of brain injury. The first model was the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. The second model was middle cerebral artery occlusion (MCAO) model of stroke. Additionally, we investigated the phenotype of BMDCs in the brain at various times following injury.; In the MPTP model, we observed a robust neuroinflammatory response characterized by astrocyte and microglia activation and increased immunoreactivity. MPTP intoxication resulted in dopaminergic neuron death in the substantia nigra by 7 days following injection. We observed a twofold increase in BMDC number in the striatum and Substantia nigra, the two areas associated with neuron degeneration. This increase in cell number was also observed in septum and hippocampus. In striatum, substantia nigra and septum the increase in BMDC number was transient and returned to control levels one week following MPTP injection. BMDCs in CNS were microglia as assessed by both morphology and cell type specific markers. BMDCs expressed the inducible form of nitric oxide synthase (iNOS), suggesting that bone marrow-derived cells play a deleterious role in neurodegeneration.; In the MCAO model of stroke, we observed massive cell death as well as ischemia induced angiogenesis. BMDC infiltration reached significant numbers 2 days following MCAO. BMDC numbers peaked at 7 days and persisted through 14 days, the last time point investigated. We observed two BMDC populations, parenchymal and vascular associated. Parenchymal BMDCs were characterized as microglia based on marker expression. We characterized vasculature associated BMDCs as pericytes based on their position relative to the endothelial basal lamina and expression of desmin, vimentin, and smooth muscle actin. Bone marrow-derived pericytes expressed growth factors associated with angiogenesis and were closely associated with the angiogenic response following ischemia, suggesting that pericytes are recruited from the peripheral circulation where they participate in ischemia induced angiogenesis.