Interaction of Isoflurane, Tumor Necrosis Factor-[alpha] and [beta]-Amyloid on Long-Term Potentiation in Rat Hippocampal Slices.

BACKGROUND: The relationship between inhalational anesthetics such as isoflurane and cognitive impairment in the elderly is controversial. Both [beta]-amyloid peptide (A[beta]), associated with Alzheimer disease, and tumor necrosis factor-[alpha] (TNF-[alpha]), a proinflammatory stress-related peptide, impair the synaptic function. We hypothesized that transient exposure to isoflurane and these peptides would impair synaptic function, manifest as a depression of long-term potentiation (LTP) and paired pulse facilitation (PPF), in the rat hippocampus. METHODS: Hippocampal slices were prepared from 3- to 4-week-old male Wistar rats. Preliminary experiments identified minimal concentrations of A[beta]1-42 peptide and TNF-[alpha] that produced statistically detectable suppressing effects on LTP (600 nM A[beta]1-42 and 5 ng/mL TNF-[alpha]). These concentrations of peptides were applied to slices alone, with 1.5% isoflurane, or in combination for 1 hour and then washed out. Measurements of LTP (field excitatory postsynaptic potentials [fEPSPs]) from neurons in the CA1 area by stimulation of the Schaffer-Collateral pathway were made after high-frequency stimulation (100 Hz, 1 second). Analysis of variance with correction for multiple comparisons was used to compare LTP under steady-state conditions and averaged for the 40- to 60-minute period after LTP induction. RESULTS: EPSP amplitude after LTP induction was 155% +/- 9% of baseline and was not affected by isoflurane exposure and washout (150% +/- 4% of baseline, P = .47). Both A[beta]1-42 and TNF-[alpha] reduced LTP by approximately 15% compared with control (129% +/- 7% and 131% +/- 11% of baseline respectively, means +/- SD, both P

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