Role of inhibition in chronic cerebral hypoperfusion

Lali H S Sekhon, Ian Spence, Michael K. Morgan*, Neville C. Weber

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Chronic reductions in cerebral blood flow (CBF) of between 25 and 50% maintained for 26 weeks impair neuronal function, through a mechanism which is not known, but which is now explored. Increased GABAergic synaptic inhibition may play a role, as inhibitory interneurons are known to be relatively resistant to acute ischaemic insults. The phenomenon of tetanus-induced long-term potentiation (LTP) was previously found to be impaired in this setting, and was thus examined in the in vitro rat hippocampus in the presence of bicuculline, a specific GABAA antagonist, to evaluate the role of inhibition in the impairment of LTP in chronic cerebral hypoperfusion (CCH). Nine Sprague-Dawley rats aged 8-10 weeks had arteriovenous fistulae (AVF) surgically constructed to reduce CBF to between 25 and 50%. Ten animals were used as age-matched controls. After a further 26 weeks, 400 μm hippocampal slices were prepared. Tetanic stimulation was used in order to attempt to induce LTP. In vitro extracellular field potentials from control and AVF slices with 5 × 10 6 M bicuculline exposure and subsequent tetanic stimulation were compared. There was no statistical difference between the responses of the two groups in either scenario (P > 0.05), although LTP was in general more difficult to induce (only occurring in 60% of control animals). Possible causes of this are discussed. It is concluded that increased GABAergic synaptic inhibition does not play a role in impairment of neuronal function seen after 26 weeks of non-infarctional CCH.

Original languageEnglish
Pages (from-to)423-428
Number of pages6
JournalJournal of Clinical Neuroscience
Volume5
Issue number4
Publication statusPublished - 1998
Externally publishedYes

Keywords

  • Arteriovenous
  • Brain slices
  • Chronic cerebral hypoperfusion
  • GABA
  • Inhibition

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