Neuroprotection and Beyond: The Central Role of CB1 and CB2 Receptors in Stroke Recovery.

The endocannabinoid system, with its intricate presence in numerous cells, tissues, and organs, offers a compelling avenue for therapeutic interventions. Central to this system are the cannabinoid receptors 1 and 2 (CB1R and CB2R), whose ubiquity can introduce complexities in targeted treatments due to their wide-ranging physiological influence. Injuries to the central nervous system (CNS), including strokes and traumatic brain injuries, induce localized pro-inflammatory immune responses, termed neuroinflammation. Research has shown that compensatory immunodepression usually follows, and these mechanisms might influence immunity, potentially affecting infection risks in patients. As traditional preventive treatments like antibiotics face challenges, the exploration of immunomodulatory therapies offers a promising alternative. This review delves into the potential neuroprotective roles of the cannabinoid receptors: CB1R's involvement in mitigating excitotoxicity and CB2R's dual role in promoting cell survival and anti-inflammatory responses. However, the potential of cannabinoids to reduce neuroinflammation must be weighed against the risk of exacerbating immunodepression. Though the endocannabinoid system promises numerous therapeutic benefits, understanding its multifaceted signaling mechanisms and outcomes remains a challenge.

Creating opportunities through mentorship, parental involvement, and safe spaces (COMPASS) program: multi-country study protocol to protect girls from violence in humanitarian settings.

BACKGROUND: Violence against adolescent girls in humanitarian settings is of urgent concern given their additional vulnerabilities to violence and unique health and well-being needs that have largely been overlooked by the humanitarian community. In order to understand what works to prevent violence against adolescent girls, a multi-component curriculum-based safe spaces program (Creating Opportunities through Mentorship, Parental involvement and Safe Spaces - COMPASS) will be implemented and evaluated. The objectives of this multi-country study are to understand the feasibility, acceptability and effectiveness of COMPASS programming to prevent violence against adolescent girls in diverse humanitarian settings. METHODS/DESIGN: Two wait-listed cluster-randomized controlled trials are being implemented in conflict-affected communities in eastern Democratic Republic of Congo (N = 886 girls aged 10-14 years) and in refugee camps in western Ethiopia (N = 919 girls aged 13-19 years). The intervention consists of structured facilitated sessions delivered in safe spaces by young female mentors, caregiver discussion groups, capacity-building activities with service providers, and community engagement. In Ethiopia, the research centers on the overall impact of COMPASS compared to a wait-list group. In DRC, the research objective is to understand the incremental effectiveness of the caregiver component in addition to the other COMPASS activities as compared to a wait-list group. The primary outcome is change in sexual violence. Secondary outcomes include decreased physical and emotional abuse, reduced early marriage, improved gender norms, and positive interpersonal relationships, among others. Qualitative methodologies seek to understand girls' perceptions of safety within their communities, key challenges they face, and to identify potential pathways of change. DISCUSSION: These trials will add much needed evidence for the humanitarian community to meet the unique needs of adolescent girls and to promote their safety and well-being, as well as contributing to how multi-component empowerment programming for adolescent girls could be adapted across humanitarian settings. TRIAL REGISTRATION: Clinical Trials NCT02384642 (Registered: 2/24/15) & NCT02506543 (Registered: 7/19/15).

Validation of a Simplified Model for Subarachnoid Hemorrhage in Mice.

BACKGROUND: Subarachnoid hemorrhage (SAH) represents a severe injury to the brain and is associated with a high mortality (40%). Several experimental SAH models are described in the literature requiring specialized equipment and a high degree of surgical expertise. Our goal was to validate a simplified, cost-effective model to permit future studies of SAH. METHODS: SAH was induced by injection of homologous blood into the cisterna magna. Perfusion-fixation then perfusion of gelatinous India ink was performed. Brains and brainstems were collected and imaged for analysis of cerebral vasospasm. Triphenyl tetrazolium chloride (TTC) staining was used to analyze brain tissue cell death 24 hours following stroke. A composite neuroscore was utilized to assess SAH-related neurologic deficits. RESULTS: Anterior cerebral artery and basilary artery diameters were significantly reduced at 24 hours post SAH induction. Middle cerebral artery diameter was also reduced; however, the results were not significant. TTC staining showed no infarcted tissue. Neuroscores were significantly lower in the SAH mice, indicating the presence of functional deficits. CONCLUSIONS: This simplified model of SAH elicits pathological changes consistent with those described for more complex models in the literature. Therefore, it can be used in future preclinical studies examining the pathophysiology of SAH and novel treatment options.

Intravital Widefield Fluorescence Microscopy of Pulmonary Microcirculation in Experimental Acute Lung Injury Using a Vacuum-Stabilized Imaging System.

Intravital imaging of leukocyte-endothelial interactions offers valuable insights into immune-mediated disease in live animals. The study of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and other respiratory pathologies in vivo is difficult due to the limited accessibility and inherent motion artifacts of the lungs. Nonetheless, various approaches have been developed to overcome these challenges. This protocol describes a method for intravital fluorescence microscopy to study real-time leukocyte-endothelial interactions in the pulmonary microcirculation in an experimental model of ALI. An in vivo lung imaging system and 3-D printed intravital microscopy platform are used to secure the anesthetized mouse and stabilize the lung while minimizing confounding lung injury. Following preparation, widefield fluorescence microscopy is used to study leukocyte adhesion, leukocyte rolling, and capillary function. While the protocol presented here focuses on imaging in an acute model of inflammatory lung disease, it may also be adapted to study other pathological and physiological processes in the lung.

Caregiver parenting and gender attitudes: Associations with violence against adolescent girls in South Kivu, Democratic Republic of Congo.

Violence against adolescent girls occurs at alarmingly high rates in conflict-affected settings, in part due to their increased vulnerability from their age and gender. However, humanitarian programming efforts have historically focused either on child abuse prevention or intimate partner violence prevention and have not fully addressed the specific needs of adolescent girls, including engagement of caregivers to reduce risk of violence against adolescent girls. Thus, the objectives of this analysis are to examine the whether gendered and parental attitudes of caregivers in South Kivu, Democratic Republic of Congo (DRC) were associated with their adolescent girls' experiences of violence and girls' attitudes towards IPV. Cross-sectional data from 869 girls (10-14 years) and their caregivers (n=764) were drawn from a baseline assessment of a violence prevention evaluation conducted in 2015. Findings suggest that female caregiver's gender equitable attitudes for adults may be associated with reduced odds of sexual abuse and less acceptance of IPV for adolescent girl children. Parenting attitudes and beliefs and gender equity for girl children were not associated with violence risk for girls, while increased accepting attitudes of negative discipline were only associated with lowered odds of sexual abuse. Understanding of caregivers' attitudes may provide potential insight into how to more effectively engage and develop programming for caregivers to promote the safety and well-being of adolescent girls.

Disclosure bias for group versus individual reporting of violence amongst conflict-affected adolescent girls in DRC and Ethiopia.

Methodologies to measure gender-based violence (GBV) have received inadequate attention, especially in humanitarian contexts where vulnerabilities to violence are exacerbated. This paper compares the results from individual audio computer-assisted self-administered (ACASI) survey interviews with results from participatory social mapping activities, employed with the same sample in two different post-conflict contexts. Eighty-seven internally displaced adolescent girls from the Democratic Republic of the Congo and 78 Sudanese girls living in Ethiopian refugee camps were interviewed using the two methodologies. Results revealed that the group-based qualitative method elicited narratives of violence focusing on events perpetrated by strangers or members of the community more distantly connected to girls. In contrast, ACASI interviews revealed violence predominantly perpetrated by family members and intimate partners. These findings suggest that group-based methods of information gathering frequently used in the field may be more susceptible to socially accepted narratives. Specifically, our findings suggest group-based methods may produce results showing that sexual violence perpetrated by strangers (e.g., from armed groups in the conflict) is more prevalent than violence perpetrated by family and intimate partners. To the extent this finding is true, it may lead to a skewed perception that adolescent GBV involving strangers is a more pressing issue than intimate partner and family-based sexual violence, when in fact, both are of great concern.

Implementation of Audio-Computer Assisted Self-Interview (ACASI) among adolescent girls in humanitarian settings: feasibility, acceptability, and lessons learned.

BACKGROUND: Audio-Computer Assisted Self- Interview (ACASI) is a method of data collection in which participants listen to pre-recorded questions through headphones and respond to questions by selecting their answers on a touch screen or keypad, and is seen as advantageous for gathering data on sensitive topics such as experiences of violence. This paper seeks to explore the feasibility and acceptability of using ACASI with adolescent girls and to document the implementation of such an approach in two humanitarian settings: conflict-affected communities in eastern Democratic Republic of Congo (DRC) and refugee camps along the Sudan-Ethiopia border. METHODS: This paper evaluates the feasibility and acceptability of implementing ACASI, based on the experiences of using this tool in baseline data collections for COMPASS (Creating Opportunities through Mentorship, Parental involvement, and Safe Spaces) impact evaluations in DRC (N = 868) and Ethiopia (N = 919) among adolescent girls. Descriptive statistics and logistic regression models were generated to examine associations between understanding of the survey and selected demographics in both countries. RESULTS: Overall, nearly 90 % of girls in the DRC felt that the questions were easy to understand as compared to approximately 75 % in Ethiopia. Level of education, but not age, was associated with understanding of the survey in both countries. CONCLUSIONS: Financial and time investment to ready ACASI was substantial in order to properly contextualize the approach to these specific humanitarian settings, including piloting of images, language assessments, and checking both written translations and corresponding verbal recordings. Despite challenges, we conclude that ACASI proved feasible and acceptable to participants and to data collection teams in two diverse humanitarian settings.