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Hypoxic-ischemic tolerance in newborn rat brain

Research Project

Project/Area Number 11671071
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionMiyazaki Medical College

Principal Investigator

IKEDA Tomoaki  Miyazaki Medical College, Perinatal Center, Assistant Professor, 医学部, 講師 (80202894)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Keywordshypoxic-ischemic tolerance / hyperthermia / heat shock protein / endotherium / blood brain barrier / cerebrospinal fluid / newborn / rat / 神経栄養因子
Research Abstract

Understanding the endogenous neuroprotective mechanism is important for the prevention and treatment of hypoxic-ischemic brain damage in fetus and neonate, a major cause of childhood handicaps. We found the sublethal hypoxic or hypoerthermic preconditioning of 7-day-old rats reduced the severity of brain injury produced by subsequent hypoxic-ischemic stress. We named this phenomenon "hypoxic-ichemic tolerance" (Ota et al. Am J Obstet Gynecol 1998 ; 179 : 1075-8, Ota et al. Journal of SGI 2000 ; 102-5).
Hyperhtermia-induced hypoxic-ischemic tolerance was observed at 6, 12, and 24 hours but not at 48 and 72 hours after hyperthermic preconditioning. Heat shock protein 72 expression in the vascular endothelial cells, rather than in the glial or neuronal cells, was most strongly associated with hypoxic-ischemic tolerance. Hyperhtermic preconditioning prevents disruption of blood-brain barrier, resulting in amelioration of hypoxic-ischemic neuronal damage. Taking all above mentioned results into account, "hypoxic-ischemic tolerance" seems to associate with the endothelial functional change in immature brain.
As another endogenous protection mechanism, we started to investigate the role of neurotrophic factors. Cerebrospinal fluid concentration of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 was measured in normal developing rat from birth to postnatal day 21 by enzyme-linked immunosorbent assay. Expression of glial cell line-derived neurotrophic factor(GDNF) in developing rat brain from postnatal day 1 to 21 was examined immunocytochemiscally. GDNF injecting into brain parenchyma provided remarkable protection against ischemic-hypoxic-induced brain damage in 7-day-old rats in a dose-dependent manner.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Ikeda T,Ikenoue T,Xia XY,Xia YX.: "Important role of 72-kd heat shock protein expression in the endothelial cell in acquisition of hypoxic-ischemic tolerance in theimmature rat."Am J Obstet Gynecol. 182(2). 380-386 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikeda T,Murata Y,Quiligan EJ,Parer JT,Murayama T,Koono M.: "Histologic and biochemical study of the brain, heart, kidney, and liver in asphyxia caused by occlusion of the umbilical cord in near-term fetal lambs."Am J Obstet Gynecol. 182(2). 449-457 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikeda T,Xia XY,Xia YX,Ikenoue T,Han B,Choi BH.: "Glial cell line-derived neurotrophic factor protects against schemia/hypoxiaind iuced brain injury in neonatal rat."Acta Neuropathol. 100. 161-167 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaneko M,Sameshima H,Ikeda T,Kodama Y,Ikenoue T.: "Antepartum evaluation of monochorionic diamniotic (MD) twins ; MD-twin score : A new scoring method for perinatal outcome."J Obstet Gynaecol Res. 26(2). 111-116 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ota A,Ikeda T,Xia XY,Xia YX,Ikenoue T.: "Hypoxic-ischemic tolerance induced by hyperthermic pretreatment in newborn rats."J Soc Gynecol Investig. 7(2). 102-105 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xia YX,Ikeda T,Xia XY,Ikenoue T.: "Differential neurotrophin levels in cerebrospinal fluid and their changes during development in newborn levels."Neuroscience Letters. 280. 220-222 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikeda T, Ikenoue T, Xia XY, Xia YX.: "Important role of 72-kd heat shock protein expression in the endothelial cell in acquisition of hypoxic-ischemic tolerance in the immature rat."Am J Obstet Gynecol. 182. 380-6 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikeda T, Murata Y, Quilligan EJ, Parer JT, Murayama T, Koono M.: "Histologic and biochemical study of the brain, heart, kidney, and liver in asphyxia caused by occlusion of the umbilical cord in near-term fetal lambs."Am J Obstet Gynecol. 182. 449-57 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikeda T, Xia XY, Xia YX, Ikenoue T, Han B, Choi BH: "Glial cell line-derived neurotrophic factor protects against ischemia/hypoxia-induced brain injury in neonatal rat"Acta Neuropathol. 100. 161-167 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaneko M, Sameshima H, Ikeda T, Kodama Y, Ikenoue T.: "Antepartum evaluation of monochorionic diamniotic(MD) twins ; MD-twin score : A new scoring method for perinatal outcome."J Obstet Gynaecol Res. 26(2). 111-116 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ota A, Ikeda T, Xia XY, Xia YX, Ikenoue T.: "Hypoxic-ischemic tolerance induced by hyperthermic pretreatment in newborn rats."J Soc Gynecol Investig. 7. 102-5 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xia YX, Ikeda T, Xia XY, Ikenoue T.: "Differential neurotrophin levels in cerebrospinal fluid and their changes during development in newborn rat."Neuroscience Letters. 280. 220-222 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tomoaki Ikeda,MD,Tsuyoma Ikenoue,MD,Xiao Y.Xia,MD,and Yix.Xia,MD: "Important role of 72-kd heat shock protein expression in the endothelial cell in acquisition of hypoxic-ischemic tolerance in the immoture rat"Am J Obstet Gynecol. 182・2. 380-386 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomoaki Ikeda,MD,Yuji Murata,MD,Edward J.Quilligan,MD,Julian T.Parer MD,PhD,Toshihiko Murayama,MD,and Masashi Koono,MD: "Histologic and biochemical study of the brain, heart, kidney, and liver in as phyxia caused by occlusion of the umbilical cord in near-term fetal lambs."Am.J Obstet Gynecol. 182・2. 449-457 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomoaki Ikeda,XiooY.Xia,Yix.Xia,Tsuyoma Ikenoue,Bora Han,Ben H.Choi: "Glial cell line-derived neurotrophic factor protects against ischemia/hypoxia-induced brain injury in neonatal rat"Acta Neuropathol. 100. 161-167 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masatoki Kaneko,Hiroshi Sameshima,Tomoaki Ikeda,Yuki Kodama and Tsuyomu kenoue: "Antepartum Evaluation of Monochorionic Diamniotic (MD) Twins ; MD-Twin score : A New Scoring Method for Perinatal Outcome"The Journal of Obstetrics and Gynaecology Research. 26・2. 111-116 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Arturo Ota,MD,Tomoaki Ikeda,MD,Xiao Y.Xia,MD,Yix.xia,MD,and Tsuyomu Ikenoue,MD: "Hypoxic-Ischemic Tolerance Induced by Hyperthermic Pretreatment in Newborn Rats."J.Soc Gynecol Investig. 7・2. 102-105 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yix xia,Tomoaki Ikeda,Xiao Y.Xia,Tsayoma Ikenoue: "Differential neurotrophin levels in cerebrospinal fluid and their changes during development in newborn rat"Neuroscience Letters. 280. 220-222 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xia XY,Ikeda T,Ota A,et al: "Heat shock protein 72 expression and microtabule-associated protein 2 disappearance after hypoxia-ischemia in the developing rat brain"Am J Obstet Gynecol. 180. 1254-1262 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda T,Abe K,Ota A,Ikenoue T.: "Heat shock protein 70 and heat shock cognate protein 70 messenger ribonucleic acid induction in the brains,hearts,and livers of neonatal rats after hypoxic stress"Am J Obstet Gynecol. 180. 457-461 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda T,Xia XY,Xia YX,Ikenoue T.: "Hyperthermic preconditioning prevents blood-brain barrier disruption produced by hypoxia-ischemia in newporn rat."Brain Res Dev Brain Res. 117. 53-58 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda T,Xia XY,Xia YX,Ikenoue T.Choi BH.: "Expression of glial cell line-derived neurotrophic factor in the brain and cerebrospinal fluid of the developing rat [In Process Citation]"Int J Dev Neurosci. 17. 681-691 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda T,Ikenoue T.Xia XY,Xia XX.: "Heat shock protein 72 expression in the endothe lial cell may play an important role in aguisition of hypoxic-ischemic tolerance in the immature rat."Am J Obstet Gynecol. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda T,Xia XY,Xia YX,Ikenoue T.Han B,Choi BH.: "Glial cell line-derived neurotrophic factor(GDNF) protects against ischemia/hypoxia-induced brain injury in neonatal rat."Acta Neuropathologica. (in print). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ota A,Ikeda T,Xia XY,Xia YX,Ikenoue T.: "Hypoxic-ischemic tolerance induced by hyperthermic pretreatment in newborn rats."Journal of SGI. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Xia XY,Ikeda T,Xia XX,Ikenoue T: "Differentiated neurotrophin levels in cerebrospinal fluid and their changes during development in newborn rat."Neuroscience Letter. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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