| Objective: The morbidity of perioperative cerebrovascular disease is increasing year by year, expecially for the elders(>65 years old) and the patients undergoing major surgeries(such as cardiac and major vascular surgeries, arthroplasty and long-term abdominal surgeries). According to statistical research, the incidence of acute ischemic stroke(AIS) is 0.7% for patients underwent colectomy, 0.2% for patients underwent total hip replacement, and 0.6% for patients underwent lobectomy. But for patients aged over 65 years old, the incidence of AIS is 1.0% for patients underwent colectomy, 0.3% for patients underwent total hip replacement and 0.8% for patients underwent lobectomy. And the higher incidence of AIS occurs for patients underwent cardiac and major vascular surgeries. Anesthesiologist should choose anesthetic prudentially. Propofol is an intravenous general anesthetic. Our previous studies have showed that propofol postconditioning enhanced the activity of phosphatidylinositol-3-kinase(PI3K) and upregulating the expression of GluR2 subunit of α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid(AMPA) receptors receptors, thus provided neuroprotection in cerebral I/R injury. γ-aminobutyric acid(GABA) and its receptors are the main inhibitory neurotransmitter systems in the central nervous systems. According to studies, the “excitotoxicity” induced by over-activation of excitatory neurotransmitter systems and/or excessive suppression of neurotransmitter systems is the main mechanism of brain damage. K+-Cl--co-transporter 2(KCC2), as a neuron Cl- extruder, can transport intracellular Cl- to the synaptic cleft and contribute to higher [Cl- ] in the synaptic cleft, which is a significant physiological foundation of GABA showing inhibitory effect for mature neurons. The aim of this study was to investigate effect of propofol postconditioning on the expression of neuronal KCC2 of ipsilateral hippocampus for I/R rats in the GABAergic inhibitory nervous system.Methods: 228 adult male Sprague-Dawley rats, aged 7-8 weeks, weighing 250-280 g, were randomly divided into 6 groups(n=38), including sham operation(Sham) group, ischemia-reperfusion(I/R) group, propofol(Pro) group, and DIOA + Sham(DIOA+Sham) group, DIOA+ischemia-reperfusion(DIOA+I/R) group, DIOA + propofol(DIOA+Pro) group. The rats in the groups with inhibitor were injected intravenously with DIOA 30 μg, 15 min before surgery. The right side middle cerebral artery occlusion(MCAO) was performed as Longa introduction. 60 min after MCAO, the suture was pulled out 10 mm to allow for reperfusion. Regarding groups Pro and DIOA+Pro, at the onset of reperfusion, propofol was infused intravenously at a speed of 20 mg·kg-1·h-1 by a syringe pump for 2 hours duration. After 24 h of reperfusion, the mNSS(modified neurological severity score) and the percentage of cerebral infarct volume were measured; after 24 h of reperfusion, Nissl staining was performed to survey the number of surviving neurons in hippocampal CA1 area; after 24 h of reperfusion, The rat brains were removed to evaluate the density of hippocampal dendritic spines in the ipsilateral CA1 area by Golgi staining; after 24 h of reperfusion, coronal hippocampal slices were used to survey the varieties of KCC2 in inhibitory interneuron Glutamic acid decarboxylase 67(GAD67); after 24 h of reperfusion, general KCC2 expression was assessed via Western blotting.Results: After 24 h of reperfusion, comparing with I/R group, propofol postconditioning at dose of 20mg·kg-1·h-1 reduced the neurological behavioral scores, the cerebral infarct volume and the density of spines(P<0.05), and increased the number of surviving neurons, which implied that propofol postconditioning can provide acute protection against IR injury. Additionally, the expression of inhibitory interneuronal KCC2 was up-regulated significantly(P<0.05) via propofol postconditioning. Compared with group I/R, there was significant difference for all the results in group DIOA+I/R(P<0.01 or P<0.05). Compared with group Pro, the scores of mNSS, volume of cerebral infarct and density of spines had a increasing trend, while the number of surviving neurons and the expression of inhibitory interneuronal KCC2 significantly decreased(P<0.01 or P<0.05). That means the protection and corresponding mechanism inhibited by DIOA partly.Conclusion: Propofol postconditioning at dose of 20mg·kg-1·h-1 provides a neuroprotective effect, which mechanism may be related to upregulation of inhibitory interneuronal KCC2 expression, which was one of significant mechanisms of acute(24h) neuroprotection afforded by propofol postconditioning. |
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