Sevoflurane protects against cerebral ischemia/reperfusion injury via microrna-30c-5p modulating homeodomain-interacting protein kinase 1

Abstract

Sevoflurane (SEV) has been reported to be an effective neuroprotective agent for cerebral ischemia/reperfusion injury (CIRI). However, the precise molecular mechanisms of Sev preconditioning in CIRI remain largely unknown. Therefore, CIRI model was established via middle cerebral artery occlusion method. SEV was applied before modeling. after successful modeling, lentivirus was injected into the lateral ventricle of the brain. Neurological impairment score was performed in each group, and histopathologic condition, infarct volume, apoptosis, inflammation, oxidative stress, microRNA (miR)-30 c-5p and homeodomain-interacting protein kinase 1 (HIPK1) were detected. Mouse hippocampal neuronal cell line HT22 cells were pretreated with SEV, and the in vitro model was stimulated via oxygen-glucose deprivation and reoxygenation. The corresponding plasmids were transfected, and the cell growth was detected, including inflammation and oxidative stress, etc. The targeting of miR-30 c-5p with HIPK1 was examined. The results clarified that reduced miR-30 c-5p and elevated HIPK1 were manifested in CIRI. SEV could improve CIRI and modulate the miR-30 c-5p-HIPK1 axis in vitro and in vivo , and miR-30 c-5p could target HIPK1. Depressed miR-30 c-5p could eliminate the protection of SEV in vitro and in vivo . Repression of HIPK1 reversed the effect of reduced miR-30 c-5p on CIRI. Therefore, it is concluded that SEV is available to depress CIRI via targeting HIPK1 through upregulated miR-30 c-5p.

Emerging Role of MicroRNA-30c in Neurological Disorders

“…The previous observations substantiate these findings showing that SOX9 deletion in mice imparted a protective effect against transient middle cerebral artery occlusion injury, resulting in improved post-stroke neurological recovery and neuroprotection [73]. From in vitro oxygen-glucose deprivation and reperfusion models, it is evident that miR-30c targets 3 UTR of SOX9 [44], homeodomain-interacting protein kinase 1 (HIPK1) [72], and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) [74] gene, which might attenuate oxidative stress and inflammation. Experimental data revealed that "miR-30c-5p antagomir" enhanced oxidative stress, inflammation, infarct area, and neurological deficits in a transient middle cerebral artery occlusion rat model.…”

“…Experimental data revealed that "miR-30c-5p antagomir" enhanced oxidative stress, inflammation, infarct area, and neurological deficits in a transient middle cerebral artery occlusion rat model. These effects were prevented by the upregulation of miR-30c-5p by sevoflurane or flurbiprofen axetil pretreatments [44,72]. MiR-30c-5p attenuates pathological pathways such as mitogen-activated protein kinases by targeting ROCK2 [74], which presents a novel therapeutic target, miR-30c/ROCK2, in the pathogenesis of stroke.…”

“…This decrease in expression of miR-30c is associated with the acute phase of stroke rather than the recovery phase after the stroke which also suggests the biomarker potential of miR-30c in stroke. However, a large body of pre-clinical data indicates that downregulation of miR-30c-5p expression in the brain potentiates degenerative mechanisms, resulting in an increase in infarct area [43,44,72]. In a study, "miR-30c mimic" pretreatment caused hippocampal neuroprotection, neurological improvement, and a decrease in infarct area in rats against transient middle cerebral artery occlusion.…”

Sevoflurane Postconditioning Attenuates Cerebral Ischemia-Reperfusion Injury by Inhibiting SP1/ACSL4-Mediated Ferroptosis

“…Sevoflurane is an effective neuroprotective agent for cerebral I/R injury. 12,13 Sevoflurane treatment has been reported to reduce neurological impairment, cerebral infarction volume, and inflammatory cytokine levels. Sevoflurane has also been shown to reduce neuronal apoptosis and antioxidant stress.…”

“…It has been reported that sevoflurane reduced neurological impairment, cerebral infarction volume, and inflammatory cytokine levels. [10][11][12] At the same time, sevoflurane has been shown to reduce neuronal apoptosis and antioxidant stress. [13][14][15] Sevoflurane plays a protective role in neuronal HIBI by inhibiting apoptosis and necrosis.…”