ABSTRACT
Objective:To evaluate the effects of sevoflurane combined with propofol anesthesia on the synaptic plasticity in the hippocampus after operation in rats with mild cognitive impairment (MCI) and the relationship with potassium-chloride cotransporter-2 (KCC2)/sodium-potassium-chloride cotransporter 1 (NKCC1).Methods:Clean-grade healthy male Sprague-Dawley rats, aged 16-18 months, weighing 440-540 g, in which MCI was induced by severe bilateral common carotid artery stenosis (BCAS). Forty-eight rats with MCI were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sevoflurane anesthesia group (group S), propofol anesthesia group (group P), and sevoflurane and propofol anesthesia group (group SP). After disappearance of eyelash reflex, open reduction and internal fixation was performed after tibial fracture was induced in S, P and SP groups.Anesthesia method was as follows: 1.7% sevoflurane was inhaled and propofol 20 mg·kg -1·h -1 was intravenously infused for 3 h in group SP, 3% sevoflurane was inhaled for 3 h in group S, and propofol was intravenously infused at rate of 40 mg·kg -1·h -1 for 3 h in group P. The novel object recognition (NOR) test was performed at 14 days after operation, and the discrimination index in NOR test was calculated.The in vivo electrophysiological experiment was performed on 19 days after operation to measure long-term potentiation and amplitude of the field excitatory postsynaptic potential (fEPSP). The expression of KCC2 and NKCC1 was determined by Western blot, and the ratio of KCC2/NKCC1 was calculated.The density of dendritic spines in the hippocampal CA1 region was determined by Golgi-COX staining performed at 30 days after operation. Results:Compared with Sham group, the discrimination index in NOR test, hippocampal KCC2/NKCC1 ratio, density of dendritic spines in hippocampal CA1 region, and amplitude of fEPSP were significantly decreased in S and P groups ( P<0.05), and no significant change was found in the parameters mentioned above in group SP ( P>0.05). Compared with group S or group P, the discrimination index in NOR test, hippocampal KCC2/NKCC1 ratio, density of dendritic spines in hippocampal CA1 region, and amplitude of fEPSP were significantly increased in group SP ( P<0.05). Conclusion:Sevoflurane combined with propofol anesthesia does not aggravate postoperative cognitive dysfunction in the rats with MCI, which may be related to maintaining the balance of hippocampal KCC2/NKCC1 and protecting the synaptic plasticity in hippocampi.
ABSTRACT
As the populations are aging, concerns about cognitive decline are becoming a common topic in medical consultations. The occurrence of postoperative cognitive change involves many factors such as their own situation and perioperative period. Alzheimer′s disease (AD) is the main concern about postoperative cognitive change. For years it was widely believed that cognitive dysfunction caused by anesthesia, some studies suggest that anesthetics may cause mitochondrial damage, while most studies suggest that mitochondrial dysfunction may affect AD. But it is rarely noticed, that cells can maintain the stability following mitochondrial stress by a series of integrated stress responses (ISR) and alleviate mitochondrial stress in progeny. We reviewed the research progress of mitochondrial stress in AD.