Lactate utilization as an energy substrate in ischemic and thermal preconditoned rat brain slices

• Project/Area Number: 13671594
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Oita Medical University
• Principal Investigator: KITANO Takashi Oita Medical University, Anesthesiology, Associate Professor, 医学部, 助教授 (20211196)
• Co-Investigator(Kenkyū-buntansha): 山田 直子(西丸 直子) (山田 直子(西丸)) 大分医科大学, 医学部, 助教授 (60101086) ; IWASAKA Hideo (NISHIMARU Naoko) Oita Medical University, Anesthesiology, Associate Professor, 医学部, 助教授 (90175216)
• Project Period (FY): 2001 – 2002
• Project Status: Completed(Fiscal Year 2002)
• Budget Amount: ¥2,900,000 (Direct Cost : ¥2,900,000); Fiscal Year 2002 : ¥1,400,000 (Direct Cost : ¥1,400,000); Fiscal Year 2001 : ¥1,500,000 (Direct Cost : ¥1,500,000)
• Keywords: Ischemic preconditioning / ^<31>P NMR / Lactate / 高炭酸アシドーシス

Research Abstract

We examined the utilization of lactate as an energy substrate in ischemic or thermal preconditioned brain slices. The ischemic preconditioned slices were obtained from left hemisphere, of which the contralateral middle cerebral artery was occluded 48h before the slice preparation. The thermal preconditioned slices were obtained from the rat, which was exposed to heat stroke (42-43^。C for 15min) at 48h before the preparation. The levels of high-energy phosphates in brain slices were measured by using ^<31>P NMR with a time resolution of 8 min at 25^。C. When iodoacetic acid-pretreated brain slices were further treated with fluorocitrate, glial toxin, for 2h (neuron-rich slices), the recovery of the phosphocreatine (PCr) level in artificial cerebrospinal fluid (ACSF) containing lactate after high-K^+ stimulation was completely abolished in intact slices, whereas the PCr level in the ischemic or the thermal preconditioned slices partly recovered in otherwise similar conditions as above (n=6). These results indicated that neurons, which preconditioned with ischemia or the heat stroke, acquired the ability to utilize lactate as an energy substrate. In parallel experiments we recorded population excitatory postsynaptic potentials and spikes from granule cells in hippocampal slices. Population spikes of intact slices in ACSF containing lactate were completely abolished in 30 min and did not recover after intact slices were re-perfused with standard ACSF, but those of the ischemic or the thermal preconditioned slices were able to recover in standard ACSF (n=6). These results show that the ischemic and the thermal preconditioning may induce certain systematic changes in neurons, such as the expression of lactate transporters and/or the activation of lactate dehydrogenase.

Research Products

• [Publications] Kitano, T., Yoshioka, K., Nisimaru, N., Iwasaka, H, Noguchi, T.: "Neurons in brain slices obtained from ischemic preconditined rats can utilize lactate as energy source"Anesthesiology. 93. A-728 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kitano, T., Nakamura, T., Kawabe, S., Iwasaka, H., Nisimaru, N., Noguchi, T.: "Fall in high energy phosphate levels during intracellular acidosis is inhibited by preconditioning in rat brain slices"Anesthesia & Analgesia. 94. S-111 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kitano, T., Nisimaru, N., Sibata, E., Iwasaka, H., Noguchi, T., Yamada, K.: "Lactate utilization as an energy substrate in ischemic preconditioned rat brain slices"Life Sciences. 72. 557-564 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kitano, T., Nisimaru, N., Kawabe, S., Nakamura, T., Iwasaka, H., Noguchi, T.: "Effects of intracellular acidosis on the steady atate rates of creatine kinase in rat brain slices"Anesthesia & Analgesia. 96. S-172 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kitano, T., Nisimaru, N., Hayashi, E., Iwasaka, H., Noguchi, T., Yokoi, I.: "Monocarboxylates and glucose utilization as energy substrates in rat brain slices under selective glial poisoning -a^<31>P NMR study"Molecular and Cellular Biochemistry. 244. 77-81 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kitano, T., Nisimaru, N., Sibata, E., Iwasaka, H., Noguchi, T., Yamada, K.: "Lactate utilization as an energy substrate in ischemic preconditioned rat brain slices"Life Science. 72. 557-564 (2002)
• [Publications] Kitano, T., Nishimaru, N., Hayashi, E., Iwasaka, H., Noguchi, T., Yokoi, I.: "Monocarboxylates and glucose utilization as energy substrates in rat brain slices under selective glial poisoning-a ^<31>P NMR study"Molecular and Cellular Biochemistry. 244. 77-81 (2003)