Infarct tolerance induced by repetitive cortical spreading depression is reproduced by prolonged intracerebral infusion of recombinant brain-derived neurotrophic factor

Summary: Molecular mechanisms in infarct tolerance, the consistently increased cerebral resistance to ischemic stroke within 12 days following repetitive cortical spreading depression (CSD), were analyzed by measuring brain derived neurotrophic factor (BDNF)-content in the neocortex in rats. The levels of total BDNF protein were significantly elevated from day 0 to 12, peaking on days 0 and 6 following CSD. In contrast, the BDNF-like immunoreactivity in neuronal nuclei observed by confocal laser-scanning microscopy linearly increased until day 12. This indicated that the upregulation of BDNF and subsequent intranuclear translocation of BDNF-like protein was a key feature in infarct tolerance. Furthermore, it was confirmed that continuous and prolonged intracerebral infusion of exogenous recombinant BDNF induced infarct tolerance with similar histological findings of enhanced nuclear immunoreactivity for BDNF following CSD.