ABSTRACT
Avenanthramides are a group of phenolic alkaloids that have been shown to have anti-inflammatory, anti-oxidant, anti-atherogenic, and vasodilation effects. The aim of the present study was to investigate the neuroprotective effect of avenanthramide-c (Avn-c) in focal brain ischemia and reperfusion injury using middle cerebral artery occlusion (MCAo) model with mice. Male C57BL/6 mice were divided into 4 groups: sham, control (MCAo), Avn-c, and Avn-c + LY294002 (phosphoinositide 3-kinase inhibitor) group. They were subjected to 60 min MCAo followed by reperfusion. Brain infarct volume and neurological deficit scores were measured after 24 h of reperfusion. We evaluated the blood brain barrier (BBB) integrity (ZO-1, VE-cadherin and occludin) and apoptosis (Bax, Bcl2, caspase3, Cytochrome C, and poly ADP ribose polymerase(PARP)-1). We also measured GSK3ß for evaluation of the downstream mechanism of Akt. We examined the effect of the Avn-c in the phosphoinositide 3-kinase pathway. Avn-c reduced neurological score and infarction size. Avn-c inhibited the MCAo-induced disruption of tight junction proteins. Avn-c decreased apoptotic protein expression (Bax, Cytochrome C, and cleaved PARP-1) and increased anti-apoptotic protein expression (Bcl2) after MCAo. Akt and GSK3ß were decreased in MCAo group and were restored in Avn-c group. This effect of Avn-c was abolished by PI3K inhibitor. In summary, Avn-c showed neuroprotective effects through PI3K-Akt-GSK3ß signaling pathway.
ABSTRACT
BACKGROUND: The monitoring of regional cerebral oxygen saturation (SrO2) using near-infrared spectroscopy is useful method to detect cerebral ischemia during. Sevoflurane and propofol decrease cerebral metabolic rate (CMRO2) in a similar manner, but the effects on the cerebral blood flow (CBF) are different. We hypothesized that the effects of sevoflurane and propofol on SrO2 were different in patients with deficits of CBF. This study compared the effect of sevoflurane and propofol on SrO2 of patients undergoing cerebral endarterectomy (CEA). METHOD: Patients undergoing CEA were randomly assigned to the sevoflurane or propofol group (n = 74). The experiment was preceded in 2 stages based on carotid artery clamping. The first stage was from induction of anaesthesia to immediately before clamping of the carotid artery, and the second stage was until the end of the operation after clamping of the carotid artery. Oxygen saturation (SrO2, SpO2), haemodynamic variables (blood pressure, heart rate), respiratory parameters (end-tidal carbon dioxide tension, inspired oxygen tension), concentration of anesthetics, and anesthesia depth (bispectral index score) were recorded. RESULTS: During stage 1 period (before carotid artery clamping), the mean value of the relative changes in SrO2 was higher (P = 0.033) and the maximal decrease in SrO2 was lower in the sevoflurane group compared with the propofol group (P = 0.019) in the contralateral (normal) site. However, there is no difference in ipsilateral site (affected site). SrO2 decreased after carotid artery clamping and increased after declamping, but the difference was not significant between two groups. Changes in mean arterial blood pressure was lower in sevoflurane group than propofol group after the carotid artery declamping (P = 0.048). CONCLUSION: Propofol-remifentanil anesthesia was comparable with sevoflurane-remifentanil anesthesia in an aspect of preserving the SrO2 in patients undergoing carotid endarterectomy. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02609087 , retrospectively registered on November 18, 2015.
