Calcium and increase excitability promote tolerance against anoxia in hippocampal slices

Miguel A. Pérez-Pinzón, James G. Born, José M. Centeno

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

We have previously demonstrated that anoxic preconditioning (APC) protects against a subsequent otherwise 'lethal' anoxic insult in hippocampal slices. Tested here are two hypotheses: (a) APC requires calcium to improve electrical recovery in hippocampa slices; and (b) mild excitation promotes preconditioning neuroprotection. Control hippocampal slices were given a single 'test' anoxic insult followed by reoxygenation. Experimental slices were preconditioned by three short anoxic insults of 1 min separated by 10 min of reoxygenation. At 30 min after the third 'conditioning' insult, slices underwent a 'test' anoxic insult [1 min of anoxic depolarization (AD)], and then slices were reoxygenated. Evoked potentials (EPs) were recorded throughout the experiment. In other slices, APC was emulated by inducing spreading depression (as determined by a negative DC shift) with KCL or by inducing increased neuronal excitability with the excitatory agent 8- cyclopentyl-1,3-dipropylxanthine (DPCPX) (an adenosine A1 receptor blocker). 'Test' anoxic insults lasted 2 min of AD in these groups. To determine the role of calcium during APC, extracellular CaCl2 was decreased to 0.5 mM but only during the APC episodes ('test' anoxia, 1 min of AD). EP amplitudes recovered significantly better after anoxia in preconditioned slices, and in KCl- and DPCPX-treated slices (147.2 ± 33.3, n = 8, ** p < 0.01, 71.7 ± 13.5, n = 7, ** p < 0.01, and 117.8 ± 37.3, n = 5, *** p < 0.001, respectively) compared to controls. Decreases in extracellular CaCl2 during APC blocked the recovery of EPs after 'test' anoxia (80.6 ± 23.0, n = 8). These data confirm that increases in excitability can emulate APC. These data also demonstrate that calcium influx during preconditioning is required for the induction of tolerance during APC.

Original languageEnglish (US)
Pages (from-to)20-26
Number of pages7
JournalBrain Research
Volume833
Issue number1
DOIs
StatePublished - Jun 26 1999

Keywords

  • Adenosine
  • Anoxia
  • Hippocampus
  • Ischemia
  • Tolerance

ASJC Scopus subject areas

  • Neuroscience(all)

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