ABSTRACT
Cerebral ischemia/reperfusion (I/R) injury increases blood-brain barrier (BBB) permeability, leading to hemorrhagic transformation and brain edema. Normobaric oxygen (NBO) is a routine clinical treatment strategy for this condition. However, its neuroprotective effects remain controversial. This study investigated the effect of different NBO concentrations on I/R injury and explores the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the underlying mechanism. A mouse middle cerebral artery occlusion (MCAO) model, and an oxygen and glucose deprivation (OGD) model featuring mouse brain microvascular endothelial cells (ECs) called bEnd.3, were used to investigate the effect of NBO on I/R injury. A reactive oxygen species (ROS) inducer and Nrf2-knockdown by RNA were used to explore whether the Nrf2 pathway mediates the effect of NBO on cerebrovascular ECs. In the early stage of MCAO, 40% O2 NBO exposure significantly improved blood perfusion in the ischemic area and effectively relieved BBB permeability, cerebral edema, cerebral injury, and neurological function after MCAO. In the OGD model, 40% O2 NBO exposure significantly reduced apoptosis, inhibited ROS generation, reduced ER stress, upregulated the expression of tight junction proteins, and stabilized the permeability of ECs. Blocking the Nrf2 pathway nullified the protective effect of 40% O2 NBO on ECs after OGD. Finally, our study confirmed that low concentrations of NBO have a neuroprotective effect on I/R by activating the Nrf2 pathway in ECs.
ABSTRACT
BACKGROUND: While buprenorphine/naloxone (B/N) is approved for opioid use disorder treatment, effective delivery of B/N comes with significant challenges. Most notably, many patients do not take medication daily as prescribed; this non-adherence worsens treatment outcomes, increases healthcare costs, and leads to persistent worries of diversion among providers and policymakers. The present study examines the feasibility, usability, and acceptability of MySafeRx-a mobile technology platform integrating motivational coaching, adherence monitoring, and electronic pill dispensing designed to address the challenges of office-based opioid treatment (OBOT) with B/N. METHODS: The MySafeRx platform integrates electronic pill dispensers, text-messaging, and videoconferencing to provide supervised self-administration of medication and daily motivational coaching through an Android app interface. High-risk early adults (18-39 years old) who were enrolled in OBOT with B/N and had documented illicit opioid use in the past month during opioid agonist therapy (n = 12) participated in a 28-day single-arm observational study of the MySafeRx platform in addition to standard care. RESULTS: Two-thirds of participants who completed the study achieved an average of > 5 days per week of supervised B/N self-administration. Visual confirmation of medication adherence was demonstrated for an average of 72% of study days among all participants. All participants achieved platform technical proficiency within 60 min, reporting good levels of usability and acceptability. Illicit opioid abstinence rates confirmed by urine toxicology increased by 53% during MySafeRx but fell 43% within 3 weeks post-intervention. CONCLUSION: The MySafeRx medication adherence and remote coaching mobile platform is acceptable and can be feasibly implemented in real-world opioid use disorder treatment settings during high-risk periods (i.e., initial stabilization, after illicit opioid lapse), resulting in reduced illicit opioid use; however, the effect did not last after intervention completion, suggesting longer duration or extended taper of program may be needed. ClinicalTrials.Gov NCT02942199 10/24/16 https://clinicaltrials.gov/ct2/show/NCT02942199.