The Protective Effects of Benzbromarone Against Propofol-Induced Inflammation and Injury in Human Brain Microvascular Endothelial Cells (HBMVECs).

It has been widely reported that severe neurotoxicity can be induced by the application of propofol, which is closely related to the disruption of the blood-brain barrier (BBB) induced by inflammation and injury in the human brain microvascular endothelial cells (HBMVECs). Benzbromarone is a classic anti-gout agent that has been recently reported to exert anti-inflammatory and anti-oxidative stress effects. In the present study, we aim to investigate the protective property of Benzbromarone against propofol-induced injury on HBMVECs and the underlying mechanism. CCK8 assay was used to detect the cell viability of treated HBMVECs. Oxidative stress in HBMVECs was evaluated by measuring the levels of MDA and mitochondrial ROS. ELISA and qRT-PCR assay were used to determine the production of IL-1ß, IL-8, MCP-1, ICAM-1, and VCAM-1 by treated HBMVECs. Calcein-AM staining was utilized to evaluate the attachment of U937 monocytes to HBMVECs. The expression level of Egr-1 was determined by qRT-PCR and Western blot assay. Firstly, the decreased cell viability of HBMVECs induced by propofol was significantly elevated by treatment with Benzbromarone. The increased levels of MDA and mitochondrial ROS induced by propofol were dramatically suppressed by Benzbromarone. Secondly, the excessive production of inflammatory factors (IL-1ß, IL-8, and MCP-1) and adhesion molecules (ICAM-1 and VCAM-1) triggered by propofol was pronouncedly inhibited by Benzbromarone. Benzbromarone ameliorated propofol-induced attachment of U937 monocytes to HBMVECs. Lastly, Benzbromarone downregulated propofol-induced expression of the transcriptional factor Egr-1 in HBMVECs. Benzbromarone protected against propofol-induced inflammation and injury through suppressing Egr-1 in human brain vascular endothelial cells.

MicroRNA-29a-3p strengthens the effect of dexmedetomidine on improving neurologic damage in newborn rats with hypoxic-ischemic brain damage by inhibiting HDAC4.

OBJECTIVE: Hypoxic-ischemic brain damage (HIBD) is a common brain injury caused by hypoxia or ischemia of the brain. This study aims to investigate the effect of dexmedetomidine (Dex) post-treatment on neurological impairment of newborn rats with HIBD via modulating microRNA-29a-3p (miR-29a-3p) and histone deacetylase 4 (HDAC4). METHODS: HIBD model of newborn rats was established. Newborn modeled rats were injected with Dex, miR-29a-3p mimic or HDAC4 siRNA to figure their roles in learning and memory abilities, left hemisphere atrophy, brain tissue injury, inflammatory response and apoptosis rate of nerve cells of rats. The expression of miR-29a-3p and HDAC4 in hippocampal tissues of rats were detected, and the potential relationship between miR-29a-3p and HDAC4 was analyzed. RESULTS: Decreased miR-29a-3p and elevated HDAC4 were found in hippocampal tissues of rats with HIBD. In addition, Dex, elevated miR-29a-3p or declined HDAC4 enhanced spatial learning and memory abilities in rats with HIBD. Moreover, Dex, up-regulated miR-29a-3p or declined HDAC4 alleviated brain atrophy, repressed brain tissue injury, retrained the inflammation, repressed the apoptosis of neurons in the hippocampal region of rats with HIBD. HDAC4 was targeted and negatively regulated by miR-29a-3p. CONCLUSION: The study concludes that miR-29a-3p strengthened the effect of Dex on improving neurologic damage in newborn rats with HIBD by inhibiting HDAC4.