Metformin's protection against blood-brain barrier disruption and neuronal dysfunction under oxygen-glucose deprivation and tobacco smoke and e-vape chemical exposure
Abstract
BACKGROUND: According to our previous findings, the integrity of the blood-brain barrier (BBB) is affected by tobacco smoke (TSe) and electronic cigarette (ECe) exposure, and metformin (MF) can counter these detrimental effects. It is unknown, therefore, if MF protects against neuronal dysfunction after BBB damage caused by either TSe or ECe alone or combined exposure (TSe and ECe) in stroke cases. Additionally, MF's ability to enter the ischemic brain during ischemic stroke is unknown. The purpose of this effort is to address these questions.
METHODS: A well-established bEnd3/astrocyte co-culture in vitro BBB model was utilized to conduct permeability studies. Normoxia and hypoxia using oxygen-glucose deprivation (OGD) conditions were used to mimic the in vitro stroke conditions. Western blot (WB) and immunofluorescence analysis were performed for relevant molecular targets. Additionally, mitochondrial dysfunction was assessed using Seahorse Mito-stress analysis using primary neurons. Also, tMCAO was performed in C57BL/6 J mice to create ischemic injury. To quantify MF in the mouse brain, a highly sensitive LC-MS/MS technique was used.
RESULTS: According to our findings, a decrease in transendothelial electric resistance (TEER) values and increased permeability coefficient (PC) for sodium fluorescein were observed in the OGD/R condition alone or when combined with TSe, ECe, or mixed exposure compared to the control group. MF pretreatment, however, protected the BBB from…
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