Infarct tolerance accompanied enhanced BDNF-like immunoreactivity in neuronal nuclei

A prolonged period (48 h) of cortical spreading depression (CSD) induced re sistance against severe focal cerebral ischemia (infarct tolerance), howeve r, the mechanism behind this is unknown. The infarct tolerance was a transi ent phenomenon; the resistance increased linearly for the initial 12 days, peaking from 12 to 15 days after a preconditioning of CSD, and was decrease d thereafter. This study examined the time course of brain-derived neurotro phic factor (BDNF), heat shock protein (hsp)27 and 70, and glial fibrillary acidic protein (GFAP) expressions after CSD in the brain. Immunohistochemi cal expression of BDNF, hsp27, hsp70, or GFAP following a prolonged period of CSD induced by KCl-infusion, or following NaCl-infusion was analyzed by regional densitometry for 24 days in the rat neocortex. In addition, BDNF p rotein was measured quantitatively by two-site ELISA assay in the neocortex (n=6 at each time point). The GFAP expression was elevated in astrocytes ( compared to the normal level of immunodensity) during the period peaking on day 3-6 following the CSD. The hsp27 immunoreactivity was also elevated in astrocytes from day 1 to 12 peaking on day 1 and 6, but there was no expre ssion of hsp70 during the period following CSD. The immunoreactivity for BD NF was elevated in neurons from day 0 to 18 peaking on day 1 and 6. The pro tein levels of BDNF in the neocortex were significantly elevated from day 0 to 12 peaking on days 0 and 6 (compared to the normal level) (P<0.05). Usi ng a laser-scanning confocal imaging system, the BDNF-like immunoreactivity in neuronal nuclei was found to increase linearly peaking on day 12, which correlated well with the development of infarct tolerance. The intranuclea r increase in BDNF-like protein might contribute to the induction of infarc t tolerance in the brain. (C) 2000 Elsevier Science B.V. All rights reserve d.