P188 Therapy in In Vitro Models of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Varied mechanisms of injury contribute to the heterogeneity of this patient population as demonstrated by the multiple published grading scales and diverse required criteria leading to diagnoses from mild to severe. TBI pathophysiology is classically separated into a primary injury that is characterized by local tissue destruction as a result of the initial blow, followed by a secondary phase of injury constituted by a score of incompletely understood cellular processes including reperfusion injury, disruption to the blood-brain barrier, excitotoxicity, and metabolic dysregulation. There are currently no effective pharmacological treatments in the wide-spread use for TBI, in large part due to challenges associated with the development of clinically representative in vitro and in vivo models. Poloxamer 188 (P188), a Food and Drug Administration-approved amphiphilic triblock copolymer embeds itself into the plasma membrane of damaged cells. P188 has been shown to have neuroprotective properties on various cell types. The objective of this review is to provide a summary of the current literature on in vitro models of TBI treated with P188.

Frequency of Injuries to Women after Sexual Offense - Relevance of a Gynecology Examination.

Introduction Up to a third of women worldwide report having experienced an act of sexual violence during their lifetime. The emergency gynecology department is often the first port of call for affected individuals. The aim of the current study was to evaluate the importance of gynecology examinations for women after a sexual offense and to evaluate the pattern of injuries sustained. Methods This study is a retrospective single center analysis of the gynecology and forensic examination reports of all women examined for a suspected sexual offense in the central emergency department of a university hospital between 2013 and 2017 (n = 692). We evaluated genital and extragenital injury patterns, age, offender profile, time of offense, and substance use, as well as the administration of post-coital contraception and post-exposure prophylaxis for HIV. Results The affected individuals had a mean age of 26 (12 - 91 years). Almost 75% of affected individuals presented within 24 hours of the reported sexual offense. Extragenital injuries were detected in 78.6% of patients and genital injuries in 28.5%. Overall, 20.1% of the women reported complete memory loss and 18.7% partial memory loss of the actual event. Risk factors for memory lapse were the consumption of alcohol and/or the (possibly non-consensual) administration of other substances acting on the central nervous system. A history of alcohol consumption by the victim (hazard ratio [HR] 1.95; 95% confidence interval [CI] 1.21 - 3.12, p = 0.006) and younger victims aged between 25 - 49 years (HR 1.75; 95% CI 1.07 - 2.85, p = 0.025) were associated with the occurrence of extragenital injuries. However, if the perpetrator was someone who was known to the affected individual, fewer extragenital injuries were sustained (HR 0.60; 95% CI 0.36 - 0.99, p = 0.046). Reports of genital injuries, associated with an older age of affected individuals and indications of anal penetration, resulted in more frequent administration of post-exposure prophylaxis (29.1% vs. 19.5%, p < 0.012) and hepatitis B (active) vaccination (40% vs. 28.5%, p < 0.028). Conclusion Emergency gynecology examinations form a fundamental component of the medical care and the assessment of affected women after a sexual offense, since almost a third of victims sustain injuries to the genital region. In addition to a detailed complete physical examination and expert forensic documentation of physical and genital injuries, victims should also be offered psychological support which is easy for them to access.

Simulated traumatic brain injury in in-vitro mouse neuronal and brain endothelial cell culture models.

Traumatic brain injury can lead to fatal outcomes such as disability and death. Every year, it affects many patients all over the world. Not only the primary ischemic event, but also the subsequent reperfusion can cause severe brain injury. This so-called ischemia/reperfusion injury combined with mechanical forces lead to cellular disruption. Hence, this paper describes a special in-vitro model, mimicking traumatic brain injury by combining both hypoxia/reoxygenation and compression to simulate ischemia/reperfusion injury as well as the mechanical effects that occur concurrently when suffering traumatic brain injury. Through this approach, stroke, concussion, and traumatic brain injury can be studied on different cell lines in a simplified way. We used two primary mouse brain cell cultures, namely neurons and endothelial cells. Our results show that for the different cell types, different timelines of hypoxia and compression need to be explored to achieve the optimal amount of cellular damage in order to effectively mimic traumatic brain injury. Thus, this model will be useful to test potential treatments of brain injury in future in-vitro studies.

Evaluation of In Vitro Neuronal Protection by Postconditioning with Poloxamer 188 Following Simulated Traumatic Brain Injury.

Traumatic brain injury (TBI) leads to morbidity and mortality worldwide. Reperfusion after ischemia adds detrimental injury to cells. Ischemia/reperfusion (I/R) injures cells in a variety of ways including cell membrane disruption. Hence, methods to improve endogenous membrane resealing capacity are crucial. Poloxamer (P) 188, an amphiphilic triblock copolymer, was found to be effective against I/R and mechanical injury in various experimental settings. The aim of this study was to establish an in vitro mouse neuronal TBI model and, further, to investigate if postconditioning with P188 directly interacts with neurons after compression and simulated I/R injury, when administered at the start of reoxygenation. Cellular function was assessed by cell number/viability, mitochondrial viability, membrane damage by lactated dehydrogenase (LDH) release and FM1-43 incorporation as well as apoptosis-activation by Caspase 3. Five hours hypoxia ± compression with 2 h reoxygenation proved to be a suitable model for TBI. Compared to normoxic cells not exposed to compression, cell number and mitochondrial viability decreased, whereas membrane injury by LDH release/FM1-43 dye incorporation and Caspase 3 activity increased in cells exposed to hypoxic conditions with compression followed by reoxygenation. P188 did not protect neurons from simulated I/R and/or compression injury. Future research is indicated.