Neurodegeneration of substantia nigra accompanied with macrophage/microglia infiltration after intrastriatal hemorrhage.

Intrastriatal hemorrhage in rats causes neurodegenaration of the substantia nigra (SN) followed by the appearance of ED1(+) cells (macrophage/microglia). ED1(+) cells were observed for at least 8 weeks after hemorrhage. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) was shown in ED1(+) cells with the expression of both brain-derived neurotrophic factor (BDNF) mRNA and BDNF, suggesting that activated-p38 MAPK(+)/ED1(+) cells would produce BDNF and may exhibit trophic effect on the degenerating neurons in the SN. However, in ELISA, BDNF protein decreased significantly in ipsilateral SN at 7 days after hemorrhage, which may be due to a dramatic decrease of BDNF immunoreactive neurons in pars compacta. Data suggest that activation of p38 MAPK in ED1(+) cells infiltrating in ipsilateral SN after hemorrhage may produce BDNF, but that the amount of BDNF produced from ED1(+) cells is insufficient for the rescue of degenerating neurons.