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Infarct tolerance accompanied enhanced BDNF-like immunoreactivity in neuronal nuclei
H Yanamoto1, I Mizuta, I Nagata
1National Cardio-Vascular Center and NCVC Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. yanamoto@ri.ncvc.go.jp
Brain Research
|September 15, 2000
Summary
Cortical spreading depression (CSD) preconditioning induces transient infarct tolerance. Brain-derived neurotrophic factor (BDNF) levels increase in neurons, particularly in the nucleus, correlating with this protective effect.
Area of Science:
- Neuroscience
- Ischemia Research
- Cellular Biology
Background:
- Prolonged cortical spreading depression (CSD) induces temporary resistance to focal cerebral ischemia (infarct tolerance).
- The underlying molecular mechanisms of this CSD-induced infarct tolerance remain largely unknown.
- Infarct tolerance is a transient phenomenon, with resistance peaking 12-15 days post-CSD.
Purpose of the Study:
- To investigate the time course of brain-derived neurotrophic factor (BDNF), heat shock proteins (hsp27, hsp70), and glial fibrillary acidic protein (GFAP) expression following CSD.
- To determine the correlation between these molecular changes and the development of infarct tolerance.
- To elucidate the role of intranuclear BDNF in mediating infarct tolerance.
Main Methods:
- Induction of prolonged CSD in rats using KCl infusion.
- Immunohistochemical analysis of BDNF, hsp27, hsp70, and GFAP expression in the neocortex over 24 days.
- Quantitative measurement of BDNF protein levels using ELISA.
- Confocal imaging to assess BDNF localization within neuronal nuclei.
Main Results:
- GFAP expression increased in astrocytes, peaking on days 3-6 post-CSD.
- hsp27 immunoreactivity was elevated in astrocytes from day 1 to 12, peaking on days 1 and 6; hsp70 was not detected.
- BDNF immunoreactivity increased in neurons from day 0 to 18, peaking on days 1 and 6. BDNF protein levels were significantly elevated from day 0 to 12, peaking on days 0 and 6.
- Intranuclear BDNF-like immunoreactivity increased linearly, peaking on day 12, correlating with infarct tolerance.
Conclusions:
- CSD induces time-dependent changes in neurotrophic and stress-related protein expression in the rat brain.
- Elevated BDNF levels, particularly the intranuclear increase, are strongly associated with the development of CSD-induced infarct tolerance.
- Intranuclear BDNF may play a crucial role in mediating neuroprotection against ischemic injury following CSD.