The Effect Of Resveratrol On Hyperbaric Oxygen-induced Convulsion And Its Mechanism

Oxygen convulsion is one of the most common complications in hyperbaric oxygen toxicity whose main symtoms include seizure attack, body's convulsion, spasm, opisthotonos, temporal stop of respire and can theathen life when it is serious. Although researchers have devoted to studying oxygen toxicity for more than a century, the precise mechanisms of hyperoxia-induced seizures remain to be determined because of the difficulty of achieving the data from inside of the hyperbaric chamber and so on. After Paul Bert firstly found oxygen-induced convulsion in 1878, lots of experiments implied that the molecular basis of it involved generation of reactive oxygen species (ROS). Others hypothesis are such as the disorder of excitory/inhibitory neurotransmitters , the disorder of cerebral vascular modulation, ROS inhibiting enzymes involved in the formation and degradation of neurotransmitters, and so on. Although hyperoxic-induced seizures have been well described, the effects of HBO on neural elements remain poorly understood. The synaptic mechanisms seem to play an important role in the development of the HBO-induced seizures. Among the main electrophysiological findings is an increase in spontaneous synaptic transmitter release, a reduction in the inhibitory transmission and enhancement of evoked excitability activity at the neuromuscular junction. HBO is known to affect most of the neurotransmitters and their enzymes, such as GABA, glutamate, Glu decarboxylase, etc. It also affects neuromodulators. Membrane-bound active transport systems are also impaired under hyperbaric oxygen, with implications on neural activity. However, the primary neural target responsible for development of hyperoxic seizures is still unknown. In addition, it is well accepted that ROS are increased under HBO, and overwhelming the body's normal antioxidant defenses may mediate the hyperoxic insult. The hyperoxic insult may be one of the most important factors leading to convulsion, which damages the membrane system of neurons and affects membrane penetration and transportion for ions Na+ and Ca2+, etc. Resveratrol,a natural product derived from plants such as grape peel, tiger's cane, etc., is a powerful antioxidant well-studied in recent years. In addition, studies indicated that resveratrol can stablize membrane's function. Resveratrol not only shortened the duration of action potential (APD), but also decreased the amplitude of action potential (APA), overshoot (OS), maximal rate of depolarization in phase 0 (Vmax) and calcium influx.According to above, we carried out the following studies:(1) To explore the effect of resveratrol (RV) on the convulsion latency and time of continuous convulsion in mice according to behavioral observation and EEG recording.(2) To determine the contents of maleic dialdehyde (MDA) and Glu in mice exposed to 5 ATA O2 after RV treatment (5 mg/kg body weight).(3) To measure contents of extracellular Glu in cultured hippocampal neurons exposed to 5 ATA O2, and to find effect of RV on the survival rate of those neurons by MTT assay.(4) To observe the electrophysiological effects of RV on single neuron in the hippocampal CA1 area in intact awake rat by using the model of extrcellular recording of a single neuron.(5) To examine the effects of RV on glutamate- or NMDA-evoked current (Iglu, Inmda) in primary cultured rat hippocampal neurons by whole-cell patch clamp technique.And the main results are as follows:(1) RV can markedly prolong the convulsion latency and postpone the outbreak time of continuous convulsion.(2) RV can also significantly cut down the contents of MDA, but cann't decrease the contents of Glu in mice brain exposed to 5 ATA O2 after RV treatment (5 mg/kg body weight).(3) RV can increase the survival rate in cultured hippocampal neurons exposed to 5 ATA O2, but doesn't have significant effect on the contents of extracellular Glu.