Acute NMDA toxicity in cultured rat cerebellar granule neurons is accompanied by autophagy induction and late onset autophagic cell death phenotype

<p>Abstract</p> <p>Background</p> <p>Autophagy, an intracellular response to stress, is characterized by double membrane cytosolic vesicles called autophagosomes. Prolonged autophagy is known to result in autophagic (Type II) cell death. This study examined the potential role of an autophagic response in cultured cerebellar granule neurons challenged with excitotoxin N-methyl-D-aspartate (NMDA).</p> <p>Results</p> <p>NMDA exposure induced light chain-3 (LC-3)-immunopositive and monodansylcadaverine (MDC) fluorescent dye-labeled autophagosome formation in both cell bodies and neurites as early as 3 hours post-treatment. Elevated levels of Beclin-1 and the autophagosome-targeting LC3-II were also observed following NMDA exposure. Prolonged exposure of the cultures to NMDA (8-24 h) generated MDC-, LC3-positive autophagosomal bodies, concomitant with the neurodegenerative phase of NMDA challenge. Lysosomal inhibition studies also suggest that NMDA-treatment diverted the autophagosome-associated LC3-II from the normal lysosomal degradation pathway. Autophagy inhibitor 3-methyladenine significantly reduced NMDA-induced LC3-II/LC3-I ratio increase, accumulation of autophagosomes, and suppressed NMDA-mediated neuronal death. ATG7 siRNA studies also showed neuroprotective effects following NMDA treatment.</p> <p>Conclusions</p> <p>Collectively, this study shows that autophagy machinery is robustly induced in cultured neurons subjected to prolonged exposure to excitotoxin, while autophagosome clearance by lysosomal pathway might be impaired. Our data further show that prolonged autophagy contributes to cell death in NMDA-mediated excitotoxicity.</p

Pediatric traumatic brain injury in the Middle East and North Africa region: a systematic review and meta-analysis to assess characteristics, mechanisms, and risk factors

Pediatric traumatic brain injury (pTBI) represents a major cause of child injuries in the Middle East and North Africa (MENA) region. This review aims to assess pTBIs in the MENA region and reports their clinical severity and outcomes. A search was conducted using major electronic databases, including Medline/Ovid, PubMed, EMBASE, Web of Science, and SCOPUS. Abstracts were screened independently and in duplicate to detect original research. The objective and study findings for each article were recorded, along with the mechanism of pTBI, patient age and sex, injury assessment tool(s) used, and outcome. A total of 1345 articles were retrieved, of which 152 met the criteria for full-text review, and 32 were included in this review. Males predominantly suffered from pTBIs (78%). Motor vehicle accidents, followed by child abuse, were the leading causes of pTBI. Overall, 0.39% of cases were mild, 0.58% moderate, 16.25% severe, and 82.27% unclassified. The mortality rate was 13.11%. Most studies used the computed tomography scan, Glasgow Coma Scale, Abbreviated Injury Scale, and Injury Severity Score as investigation methods. This review reports on the alarming rate of child-abuse-related pTBI and offers further understanding of pTBI-associated risk factors and insight into the development of strategies to reduce their occurrence, as well as policies to promote child well-being

Spillway-Induced Salmon Head Injury Triggers the Generation of Brain αII-Spectrin Breakdown Product Biomarkers Similar to Mammalian Traumatic Brain Injury

Recent advances in biomedical research have resulted in the development of specific biomarkers for diagnostic testing of disease condition or physiological risk. Of specific interest are αII-spectrin breakdown products (SBDPs), which are produced by proteolytic events in traumatic brain injury and have been used as biomarkers to predict the severity of injury in humans and other mammalian brain injury models. This study describes and demonstrates the successful use of antibody-based mammalian SBDP biomarkers to detect head injury in migrating juvenile Chinook salmon (Oncorhynchus tshawytscha) that have been injured during passage through high-energy hydraulic environments present in spillways under different operational configurations. Mortality and injury assessment techniques currently measure only near-term direct mortality and easily observable acute injury. Injury-based biomarkers may serve as a quantitative indicator of subacute physical injury and recovery, and aid hydropower operators in evaluation of safest passage configuration and operation actions for migrating juvenile salmonids. We describe a novel application of SBDP biomarkers for head injury for migrating salmon. To our knowledge, this is the first documented cross-over use of a human molecular biomarker in a wildlife and operational risk management scenario

Can, Want and Try: Parents' Viewpoints Regarding the Participation of Their Child with an Acquired Brain Injury

BACKGROUND: Acquired brain injury (ABI) is a leading cause of permanent disability, currently affecting 20,000 Australian children. Community participation is essential for childhood development and enjoyment, yet children with ABI can often experience barriers to participation. The factors which act as barriers and facilitators to community participation for children with an ABI are not well understood. AIM: To identify the viewpoints of parents of children with an ABI, regarding the barriers and facilitators most pertinent to community participation for their child. METHODS: Using Q-method, 41 parents of children with moderate/severe ABI sorted 37 statements regarding barriers and facilitators to community participation. Factor analysis identified three viewpoints. RESULTS: This study identified three distinct viewpoints, with the perceived ability to participate decreasing with a stepwise trend from parents who felt their child and family "can" participate in viewpoint one, to "want" in viewpoint two and "try" in viewpoint three. CONCLUSIONS: Findings indicated good participation outcomes for most children and families, however some families who were motivated to participate experienced significant barriers. The most significant facilitators included child motivation, supportive relationships from immediate family and friends, and supportive community attitudes. The lack of supportive relationships and attitudes was perceived as a fundamental barrier to community participation. SIGNIFICANCE: This research begins to address the paucity of information regarding those factors that impact upon the participation of children with an ABI in Australia. Findings have implications for therapists, service providers and community organisations

Restless leg syndrome in hospitalized psychiatric patients in Lebanon: a pilot study

Farid Talih,1 Jean Ajaltouni,1 Firas Kobeissy2 1Department of Psychiatry, 2Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Objectives: To characterize and describe the prevalence of restless leg syndrome (RLS) in hospitalized psychiatric patients and to investigate the correlations between patient profile and RLS.Methods: Demographic information, psychiatric diagnoses, psychotropic medication use, and history of substance use were collected from hospitalized psychiatric patients at the American University of Beirut Medical Center; Beirut, Lebanon. A validated questionnaire to evaluate RLS symptomatology was also administered to 126 participants who agreed to participate, as well as questionnaires for insomnia, depression, and anxiety symptoms. Statistical analysis was conducted to detect the prevalence of RLS among the participants and to examine correlations with RLS in a hospitalized psychiatric population.Results: Out of the 126 participants who completed the survey, RLS was detected in 18% of the participants. Of interest, RLS was also found to be associated with higher depressive symptomatology, suicidal ideation, and working night shifts. Keywords: restless leg syndrome, insomnia, depression, and anxiety symptom

Insomnia in hospitalized psychiatric patients: prevalence and associated factors

Farid Talih,1 Jean Ajaltouni,1 Hiba Ghandour,2 Ahmad Subhi Abu-Mohammad,2 Firas Kobeissy2,3 1Department of Psychiatry, American University of Beirut Medical Center, Beirut, Lebanon; 2Faculty of Medicine, American University of Beirut, Beirut, Lebanon; 3Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Objectives: To quantify and describe the prevalence of insomnia in hospitalized psychiatric patients and to investigate the associations between insomnia and demographic and clinical factors in hospitalized psychiatric patients.Methods: The participants included 203 individuals hospitalized for psychiatric treatment at an academic medical center. Demographic information, psychiatric diagnoses, current psychotropic medication use, and history of substance use were collected. Insomnia screening was performed using the Insomnia Severity Index. Depressive and anxiety symptoms were also evaluated using the Generalized Anxiety Disorder questionnaire and the Patient Health Questionnaire. Restless legs syndrome (RLS) symptoms were evaluated using the Restless Legs Syndrome Rating Scale (RLSRS). Statistical analysis was conducted to detect the prevalence of insomnia among the participants and to examine possible associations among psychiatric disorders, psychotropic medications, and RLS.Results: Out of the 203 participants that completed the survey, 67.4% were found to have insomnia and 14.3% were found to have RLS. The severity of insomnia was found to be associated with the presence of RLS, depressive and anxious symptomatology, suicidal ideation, use of selective serotonin reuptake inhibitors, and use of benzodiazepines. Keywords: insomnia, depression, anxiety, restless legs syndrom

Hydrogels for Advanced Stem Cell Therapies: A Biomimetic Materials Approach for Enhancing Natural Tissue Function

Stem-cell-based therapy is a promising approach for the treatment of a myriad of diseases and injuries. However, the low rate of cell survival and the uncontrolled differentiation of the injected stem cells currently remain key challenges in advancing stem cell therapeutics. Hydrogels are biomaterials that are potentially highly effective candidates for scaffold systems for stem cells and other molecular encapsulation approaches to target in vivo delivery. Hydrogel-based strategies can potentially address several current challenges in stem cell therapy. We present a concise overview of the recent advances in applications of hydrogels in stem cell therapies, with a focus particularly on the recent advances in the design and approaches for application of hydrogels in tissue engineering. The capability of hydrogels to either enhance the function of the transplanted stem cells by promoting their controlled differentiation or enhance the recruitment of endogenous adult stem cells to the injury site for repair is also reviewed. Finally, the importance of impacts and the desired relationship between the scaffold system and the encapsulated stem cells are discussed. - 2008-2011 IEEE.Manuscript received June 9, 2017; revised January 8, 2018 and March 14, 2018; accepted March 15, 2018. Date of publication April 12, 2018; date of current version February 15, 2019. This publication was made possible by the NPRP grant [NPRP 9-144-3-021] from the Qatar National Research Fund (a member of The Qatar Foundation) and the grant GCC-2017-005 from GCC research program. The statements made herein are solely the responsibility of the authors. W. Farhat would also like to acknowledge the partial funding for his work by the French Ministry of Europe & Foreign Affairs. A. Hasan would like to thank the Biomedical Research Center at Qatar University for its resources to Anwarul Hasan’s lab. (Corresponding authors: Anwarul Hasan; Firas Kobeissy.) W. Farhat is with the College of Natural Resources, Department of Forest Biomaterials, North Carolina State University, Raleigh, NC 27695 USA, with the Université de Lyon, Ingénierie des Matériaux Polymères (IMP), UMR CNRS 5223, Université Jean Monnet, Saint-Etienne F-42023, France, and also with the Faculty of Medicine, Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon (e-mail: [email protected])

Culture of PC12 neuronal cells in GelMA hydrogel for brain tissue engineering

Restoration of brain functions following trauma or degenerative neural diseases is considered among the greatest challenges in neurology due to the fact that the central nervous system (CNS) does not regenerate on its own. Tissue engineering offers a potential solution in developing artificial neural/brain tissues. Numerous hydrogel based biomaterials have been investigated in the field of neural tissue engineering. However, the lack of the optimum combination of mechanical and biological properties in commonly available hydrogels represents a major bottle neck in growing artificial neural tissues. In this study, 3 dimensional cell culture of PC12 neuronal cells have been investigated in methacrylated Gelatin (GelMA) hydrogel for brain tissue engineering. The cell viability and propagation of PC12 neural cell lines on GelMA-based hydrogel was tested revealing its positive effects on these cells. In addition, cytotoxicity was assessed in vivo showing that implantation of GelMA did not show any acute neurotoxic effects in mice exposed to experimental brain injury.Scopu