CD82 Aggravates Sevoflurane - Induced Neurotoxicity by Regulating TRPM7 in Developing Neurons

Abstract

Background: Sevoflurane, a commonly used anesthetic in neonatal, could induce neurotoxicity in newborn animals. CD82 was found to be involved in age-related cognitive impairment. However, the role of CD82 in sevoflurane-induced neurotoxicity remains elusive. Methods: Hippocampal neurons were isolated from neonatal rats (postnatal day 1 or 2), and then exposed to 1.8 % sevoflurane for 6, 12, 24 or 48 hours. Neurons were pre-transfected with siRNA targeting CD82 (siCD82) or co-transfected with siTRPM7 (transient receptor potential melastatin 7) and pcDNA 3.1-CD82, and then exposed with sevoflurane (1.8%, 12 hours). Cell viability of the neurons was analyzed with MTT assay, and cell apoptosis was determined by flow cytometry. Protein expression was analyzed by western blot. Results: Sevoflurane exposure decreased cell viability of the developing hippocampal neurons in a time-dependent manner. Protein expressions of CD82 and TRPM7 were increased in neurons post sevoflurane exposure in a time-dependent manner. Pre-transfection of siCD82 attenuated sevoflurane-induced decrease in cell viability and increase in cell apoptosis in the neurons. Moreover, knockdown of CD82 reversed the promoting effects of sevoflurane on protein expression of cleaved TRPM7 and cleaved caspase-3. Over-expression of CD82 aggravated sevoflurane-induced decrease in cell viability and increase in cell apoptosis in neurons, while knockdown of TRPM7 counteracted with the effects of CD82 over-expression on sevoflurane-induced developing neurons. Conclusion: Sevoflurane exposure increased the expression of CD82 and TRPM7 in developing hippocampal neurons, decreased cell viability and promoted the cell apoptosis. Knockdown of CD82 partially ameliorated sevoflurane-induced neurotoxicity by down-regulation of cleaved TRPM7 in the developing neurons.

Participation of Mind Bomb-2 in Sevoflurane Anesthesia Induces Cognitive Impairment in Aged Mice via Modulating Ferroptosis

“…1 Sevoflurane is an accepted clinical anesthetic with safety and effectiveness that has been frequently used in many types of operations for decades. 4,5 Although the cardioprotective effects of sevoflurane have been well-recognized, the anesthesia-induced cognitive deficits after surgery need more study to be explored. 6 Previous study indicated that sevoflurane administrated adult rats showed impaired spatial memory ability.…”

“…Because the etiology of POCD is related to multiple factors, including the patients, the operation, the anesthesia, or the combinations of them, its internal mechanism is complicated and largely unclear . Sevoflurane is an accepted clinical anesthetic with safety and effectiveness that has been frequently used in many types of operations for decades. , Although the cardioprotective effects of sevoflurane have been well-recognized, the anesthesia-induced cognitive deficits after surgery need more study to be explored . Previous study indicated that sevoflurane administrated adult rats showed impaired spatial memory ability. , In addition, several reports have investigated potential mechanism pathways involved in the cognitive impairments caused by sevoflurane anesthesia, including endoplasmic reticulum stress, mitochondrial stimulation, inflammation, and neuronal apoptosis. − It seems that sevoflurane more or less aggravates the cognitive deficits; however, the exact underlying mechanism behind sevoflurane-induced occurrence of POCD is still open.…”

GPR68 Improves Nerve Damage and Myelination in an Immature Rat Model Induced by Sevoflurane Anesthesia by Activating cAMP/CREB to Mediate BDNF

“…Preterm babies with immature organ systems and severe congenital defects require surgery and general anesthesia . Anesthetics, including sevoflurane, isoflurane, and propofol, have been shown to induce harmful effects on the developing brain. , For example, isoflurane induced neurocognitive deficits and neurogenetic damage in neonatal rats . Sevoflurane exposure also promoted neuroapoptosis in neonatal rats and induced impairment in learning and memory function .…”

Neuroprotective effect of AGGF1 against isoflurane-induced cognitive dysfunction in aged rats through activating the PI3K/AKT signaling pathways

“…Neuroinflammation has been reported to contribute to the progress of POCD [4,5]. Clinical studies and experimental evidence have confirmed that anti-inflammatory therapy can reduce POCD [6][7][8].…”