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Aging and the effects of MK-801 on anoxic damage in rat hippocampal slices

E L Roberts1, D Wisotzky, C P Chih

  • 1Geriatric Research, Education, and Clinical Center, Miami VA Medical Center, Miami, FL 33125, USA.

Brain Research
|June 19, 1998
PubMed

Insights

Age-related brain vulnerability to oxygen deprivation is not due to differences in N-methyl-D-aspartate (NMDA) receptor neurotoxicity. NMDA receptor blockade did not alter anoxic damage onset or recovery in adult versus aged hippocampal slices.

Area of Science:

  • Neuroscience
  • Aging Research
  • Neurotoxicity

Background:

  • The aged brain exhibits increased vulnerability to anoxic damage.
  • N-methyl-D-aspartate (NMDA) receptors are implicated in excitotoxicity and neuronal damage.

Purpose of the Study:

  • To investigate if age-related differences in NMDA receptor-mediated neurotoxicity contribute to heightened susceptibility of aged brains to anoxic injury.
  • To determine the role of NMDA receptors in the differential response to anoxia between adult and aged hippocampal tissues.

Main Methods:

  • Experiments were conducted using adult and aged hippocampal slices.
  • NMDA receptor function was blocked using the antagonist MK-801.
  • The onset of anoxic depolarization and the recovery of synaptic transmission post-anoxia were measured.

Main Results:

  • NMDA receptor blockade with MK-801 did not alter the onset of anoxic depolarization in either adult or aged hippocampal slices.
  • MK-801 administration resulted in a similar percentage improvement in postanoxic synaptic transmission recovery across both age groups.
  • The observed age-related differences in anoxic depolarization onset and recovery are not explained by NMDA receptor neurotoxicity.

Conclusions:

  • Age-related differences in NMDA receptor-mediated neurotoxicity do not account for the increased vulnerability of the aged brain to anoxic damage.
  • The findings suggest that other mechanisms underlie the heightened sensitivity of aged hippocampal tissue to oxygen deprivation.
  • Targeting NMDA receptors may not be a viable strategy to mitigate age-related anoxic brain injury.

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