Acta neuropathologica
-
Acta neuropathologica · Mar 2001
Brain-derived neurotrophic factor reduces cortical cell death by ischemia after middle cerebral artery occlusion in the rat.
Stroke is the major cause of adult brain dysfunction. In an experimental approach to evaluate the possible beneficial effects of administration of neurotrophic factors in stroke, we have used a model of distal middle cerebral artery (MCA) occlusion in adult rats. In this model, we found: (1) a permanent reduction of brain-derived neurotrophic factor (BDNF) and its full-length receptor, TrkB, in the infarcted core; (2) a transient increase in BDNF immunoreactivity in the internal region of the border of the infarct (penumbra area) at 12 h after MCA occlusion; (3) increased truncated TrkB immunoreactivity in astrocytes surrounding the area of the infarction; and (4) increased full-length TrkB immunoreactivity in scattered neurons, distant from the infarct, in ipsilateral and contralateral cortices at 24 and 48 h after MCA occlusion. ⋯ Moreover, cell death was similar in nongrafted and mock-grafted rats subjected to MCA occlusion. However, the number of cells with nuclear DNA breaks was significantly reduced in the penumbra area close to the BDNF graft in ischemic rats. Thus, our results show that BDNF specifically up-regulates its full-length TrkB receptor in cortical neurons of the penumbra area and prevents their death in an in vivo model of focal ischemia.