Analysis of ischemic tolerance in view of neurotrophic factors

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671566
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: University of Tokyo
• Principal Investigator: KAWAHARA Nobutaka University of Tokyo, Department of Neurosurgery, Assistant Professor, 医学部・附属病院, 助手 (60214673)
• Project Period (FY): 1996 – 1997
• Keywords: cerebral ischemia / neurotrophic factors / spreading depression / ischemic tolerance / BDNF / brain trauma

Research Abstract

Cortical spreading depression(CSD)is known to induce ischemic tolerance in a rat model of cerebral ischemia. CSD reduces volume of cerebral infarction in a focal ischemia model and attenuates hippocampal neuronal injury in a global ischemia model, when elicited 3 days prior to these insults. Recently, brain-derived neurotrophic factor(BDNF)has been shown to protect neurons against various insults in in vivo model. This study, therefore, investigated relationship between CSD-induced ischemic tolerance and expression of BDNF in rats. CSD was induced by applying KCl solution onto the cortex for 1 hour. For control animals, NaCl solution was used.Northern blot and in situ hybridization study showed that mRNA was dramatically upregulated biphasically in the ipsilateral cortex at 4 hours and 3 days in the CSD animals, but not in the controls. In the hippocampus, no detectable changes were not observed. For analysis of protein level, BDNF ELISA assay was performed. This study revealed that BDNF protein was also increased at 12 hours and 3 days post CSD in the ipsilateral cortex, but not in the hippocampus. The increase of BDNF mNA and protein coincided in time with the induction of ischemic tolerance in the cortex, but not in the hippocampus. These results suggested that increase of BDNF may be involved in the mechanism of endogenous mechanism of ischemic tolerance in the cortex.

Research Products

• [Publications] Kawahara, N., Croll, SD., Wiegand, SJ., Klatzo, I.: "Cortical spreading depression in-duces long-term alterations of BDNF lev-els in cortex and hippocampus distinet from lesion effect:implications for isc-hemic tolerance." Neuroscience Research. 29. 37-47 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kawahara, N., Belayeu, L., Orzi, F., C-olamgelo, V., Klatzo, I.: "Transneuronal induction of toler-ance in cerebral ischemia." Maturation Phenomenoon in Cerebr-al Ischemia II. 105-111 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kawahara, N., Belayev, L., Orzi, F., C-olangelo, V., Klatzo, I.: "Maturation Phenomenon in Cerebra-l Ischemia II:Neruonal recovery and pla-sticity,Ito U,Kirino T.Kuroiwa T.KlatzoI(eds).Springer-Verlag,Berlin Heidelberg." Transneuronal induction of toler-ance in cerebral ischemia, 105-111 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kawahara N,Croll SD,Wiegand SJ,Klatzo I: "Cortical spreading depession induces long-term alterations of BDNF levels in cortex and hippocampus distinct from lesion effect : implications for ischemic tolerance." Neurosci Res. 29. 37-47 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kawahara N,Belayv L,Orzi F,Colangelo V,Klatzo I: "Transneuronal induction of tolerance in cerebral ischemia" Maturation Phenomenon in Cerebral Ischemia II : Neruonal recovery and plasticity, Ito U,Kirino T,Kuroiwa T,Klatzo I(eds), Springer-Verlag, Berlin Heidelberg. 105-111 (1997)
  • Description: 「研究成果報告書概要(欧文)」より