Resveratrol attenuates early pyramidal neuron excitability impairment and death in acute rat hippocampal slices caused by oxygen-glucose deprivation.

Zhang H, Schools GP, Lei T, Wang W, Kimelberg HK, Zhou M.

Neural and Vascular Biology, Ordway Research Institute, Center for
Medical Science, 150 New Scotland Avenue, Albany, NY 12208, USA.

Accumulating evidence indicates that the polyphenol resveratrol
(trans-3, 5, 4″-trihydroxystibene, RVT) potently protects against
cerebral ischemia neuronal damage due to its oxygen free radicals
scavenging and antioxidant properties. However, it is unknown
whether RVT can attenuate ischemia-induced early impairment of
neuronal excitability. To address this question, we simulated
ischemic conditions by applying oxygen-glucose deprivation (OGD) to
acute rat hippocampal slices and examined the effect of RVT on
OGD-induced pyramidal neuron excitability impairment using
whole-cell patch clamp recording. 100 microM RVT largely inhibited
the 15 min OGD-induced progressive membrane potential (Vm)
depolarization and the reduction in evoked action potential
frequency and amplitude in pyramidal neurons. In a parallel neuronal
viability study using TO-PRO-3 iodide staining, 20 min OGD induced
irreversible CA1 pyramidal neuronal death which was significantly
reduced by 100 microM RVT. No similar effects were found with PQQ
treatment, an antioxidant also showing potent neuroprotection in the
rat rMCAO ischemia model. This suggests that antioxidant action per
se, is unlikely accounting for the observed early effects of RVT.
RVT also markedly reduced the frequency and amplitude of AMPA
mediated spontaneous excitatory postsynaptic currents (sEPSCs) in
pyramidal neurons, which is also an early consequence of OGD. RVT
effects on neuronal excitability were inhibited by the
large-conductance potassium channel (BK channel) inhibitor
paxilline. Together, these studies demonstrate that RVT attenuates
OGD-induced neuronal impairment occurring early in the simulated
ischemia slice model by enhancing the activation of BK channel and
reducing the OGD-enhanced AMPA/NMDA receptor mediated neuronal EPSCs.


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