The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS): Validation in Arabic and Lebanese Normative Values.

OBJECTIVE: Multiple sclerosis (MS) is often associated with cognitive deficits. Accurate evaluation of the MS patients' cognitive performance is essential for diagnosis and treatment recommendation. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS), widely used cognitive testing battery, examines processing speed, verbal and visuospatial learning, and memory. Our study aims to examine the psychometric properties of an Arabic version of the BICAMS and to provide normative values in a Lebanese sample. METHOD: The BICAMS, comprised of the Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), and a newly developed verbal learning/memory test, the Verbal Memory Arabic Test (VMAT), were administered on healthy subjects and MS patients. The sample consisted of 180 healthy individuals, of whom 63 were retested after 2-3 weeks. Forty-three MS patients matched with 43 healthy subjects based on age, sex, and years of education were assessed. A sample of 10 MS patients was also examined on two occasions. Test-retest reliability and criterion-related validity were examined, and regression-based norms were derived. RESULTS: The test-retest correlations showed good evidence of reliability with coefficients ranging between 0.64 and 0.73 in the healthy sample, and between 0.43 and 0.92 in the MS sample. The BICAMS was able to discriminate between MS patients and matched healthy participants on the SDMT and BVMT-R. Normative data were comparable to other studies. CONCLUSIONS: This new Arabic version of the BICAMS shows initial good psychometric properties. While good evidence of VMAT's reliability was shown in the healthy participants, less test-retest reliability in this tool was seen in the MS group, and partial criterion-related validity was evident. This renders further examination of the VMAT. We provide regression-based norms for a Lebanese sample and encourage the use of this battery in both research and clinical settings.

Long-term cognitive deficits after traumatic brain injury associated with microglia activation.

Traumatic Brain Injury (TBI) is the most prevalent of all head injuries. Microglia play an essential role in homeostasis and diseases of the central nervous system. We hypothesize that microglia may play a beneficial or detrimental role in TBI depending on their state of activation and duration. In this study, we evaluated whether TBI results in a spatiotemporal change in microglia phenotype and whether it affects sensory-motor or learning and memory functions in male C57BL/6 mice. We used a panel of neurological and behavioral tests and a multi-color flow cytometry-based data analysis followed by unsupervised clustering to evaluate isolated microglia from injured brain tissue. We characterized several microglial phenotypes and their association with cognitive deficits. TBI results in a spatiotemporal increase in activated microglia that correlated negatively with spatial learning and memory at 35 days post-injury. These observations could define therapeutic windows and accelerate translational research to improve patient outcomes.

Potentiating Hemorrhage in a Periadolescent Rat Model of Closed-Head Traumatic Brain Injury Worsens Hyperexcitability but Not Behavioral Deficits.

Post-traumatic epilepsy (PTE) and neurocognitive deficits are devastating sequelae of head injuries that are common in adolescents. Investigating desperately needed treatments is hindered by the difficulties in inducing PTE in rodents and the lack of established immature rat models of pediatric PTE. Hemorrhage is a significant risk factor for PTE, but compared to humans, rats are less prone to bleeding because of their rapid blood coagulation system. In this study, we promoted bleeding in the controlled cortical impact (CCI) closed-head injury model with a 20 min pre-impact 600 IU/kg intraperitoneal heparin injection in postnatal day 35 (P35) periadolescent rats, given the preponderance of such injuries in this age group. Temporo-parietal CCI was performed post-heparin (HTBI group) or post-saline (TBI group). Controls were subjected to sham procedures following heparin or saline administration. Continuous long-term EEG monitoring was performed for 3 months post-CCI. Sensorimotor testing, the Morris water maze, and a modified active avoidance test were conducted between P80 and P100. Glial fibrillary acidic protein (GFAP) levels and neuronal damage were also assessed. Compared to TBI rats, HTBI rats had persistently higher EEG spiking and increased hippocampal GFAP levels (p < 0.05). No sensorimotor deficits were detected in any group. Compared to controls, both HTBI and TBI groups had a long-term hippocampal neuronal loss (p < 0.05), as well as contextual and visuospatial learning deficits (p < 0.05). The hippocampal astrogliosis and EEG spiking detected in all rats subjected to our hemorrhage-promoting procedure suggest the emergence of hyperexcitable networks and pave the way to a periadolescent PTE rat model.

Nurses' stories from Beirut: The 2020 explosive disaster on top of a pandemic and economic crises.

The World Health Organization designated last year as the International Year of the Nurse and the Midwife. And as we know worldwide, 2020 became an unforgettable year as nurses and midwives everywhere confronted the COVID-19 pandemic. To be a nurse in 2020 was challenging and heroic, but being a nurse in 2020 in Beirut, Lebanon was so extraordinarily charged with adversity. The country witnessed in a one-year series of tragedies of epic dimensions - laying a heavy toll on front-line nurses. We present our stories as eight Lebanese nurses, giving voice to our incredible experiences and our ongoing resilience in the face of these adversities. We served in the emergency department of a Beirut city hospital after a catastrophic explosion occurred in the capital on the 4th of August 2020. We reported for duty during a disaster of immense magnitude and are now coping with the aftermath of trauma. As nurses, we have faced many traumas in our country that has experienced through war and terrorism for decades. Arising from this disaster and challenges of the pandemic, we give policy recommendations that deserve urgent attention in Lebanon and underscore the need for disaster preparation, funding, education and importantly mental health care for nurses and other health professionals with help and support of the international community.

Enhanced setup for wired continuous long-term EEG monitoring in juvenile and adult rats: application for epilepsy and other disorders.

BACKGROUND: The electroencephalogram (EEG) is a widely used laboratory technique in rodent models of epilepsy, traumatic brain injury (TBI), and other neurological diseases accompanied by seizures. Obtaining prolonged continuous EEG tracings over weeks to months is essential to adequately answer research questions related to the chronobiology of seizure emergence, and to the effect of potential novel treatment strategies. Current EEG recording methods include wired and the more recent but very costly wireless technologies. Wired continuous long-term EEG in rodents remains the mainstay approach but is often technically challenging due to the notorious frequent EEG cable disconnections from the rodent's head, and to poor signal-to-noise ratio especially when simultaneously monitoring multiple animals. Premature EEG cable disconnections and cable movement-related artifacts result from the animal's natural mobility, and subsequent tension on the EEG wires, as well as from potential vigorous and frequent seizures. These challenges are often accompanied by injuries to the scalp, and result in early terminations of costly experiments. RESULTS: Here we describe an enhanced customized swivel-balance EEG-cage system that allows tension-free rat mobility. The cage setup markedly improves the safety and longevity of current existing wired continuous long-term EEG. Prevention of EEG cable detachments is further enhanced by a special attention to surgical electrode anchoring to the skull. In addition to mechanically preventing premature disconnections, the detailed stepwise approach to the electrical shielding, wiring and grounding required for artifact-free high signal-to-noise ratio recordings is also included. The successful application of our EEG cage system in various rat models of brain insults and epilepsy is described with illustrative high quality tracings of seizures and electrographic patterns obtained during continuous and simultaneous monitoring of multiple rats early and up to 3 months post-brain insult. CONCLUSION: Our simple-to-implement key modifications to the EEG cage setup allow the safe acquisition of substantial high quality wired EEG data without resorting to the still costly wireless technologies.

Lestaurtinib (CEP-701) modulates the effects of early life hypoxic seizures on cognitive and emotional behaviors in immature rats.

Hypoxic encephalopathy of the newborn is a major cause of long-term neurological sequelae. We have previously shown that CEP-701 (lestaurtinib), a drug with an established safety profile in children, attenuates short-term hyperexcitability and tropomyosin-related kinase B (TrkB) receptor activation in a well-established rat model of early life hypoxic seizures (HS). Here, we investigated the potential long-term neuroprotective effects of a post-HS transient CEP-701 treatment. Following exposure to global hypoxia, 10 day old male Sprague-Dawley pups received CEP-701 or its vehicle and were sequentially subjected to the light-dark box test (LDT), forced swim test (FST), open field test (OFT), Morris water maze (MWM), and the modified active avoidance (MAAV) test between postnatal days 24 and 44 (P24-44). Spontaneous seizure activity was assessed by epidural cortical electroencephalography (EEG) between P50 and 100. Neuronal density and glial fibrillary acidic protein (GFAP) levels were evaluated on histological sections in the hippocampus, amygdala, and prefrontal cortex at P100. Vehicle-treated hypoxic rats exhibited significantly increased immobility in the FST compared with controls, and post-HS CEP-701 administration reversed this HS-induced depressive-like behavior (p < 0.05). In the MAAV test, CEP-701-treated hypoxic rats were slower at learning both context-cued and tone-signaled shock-avoidance behaviors (p < 0.05). All other behavioral outcomes were comparable, and no recurrent seizures, neuronal loss, or increase in GFAP levels were detected in any of the groups. We showed that early life HS predispose to long-lasting depressive-like behaviors, and that these are prevented by CEP-701, likely via TrkB modulation. Future mechanistically more specific studies will further investigate the potential role of TrkB signaling pathway modulation in achieving neuroprotection against neonatal HS, without causing neurodevelopmental adverse effects.

Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment.

As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings.

Glycosylation and other PTMs alterations in neurodegenerative diseases: Current status and future role in neurotrauma.

Traumatic brain injuries (TBIs) present a chief public health threat affecting nations worldwide. As numbers of patients afflicted by TBI are expected to rise, the necessity to increase our understanding of the pathophysiological mechanism(s) as a result of TBI mounts. TBI is known to augment the risk of developing a number of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD). Hence, it is rational to assume that a common mechanistic ground links the pathophysiology of NDs to that of TBIs. Through this review, we aim to identify the protein-protein interactions, differential proteins expression, and PTMs, mainly glycosylation, that are involved in the pathogenesis of both ND and TBI. OVID and PubMed have been rigorously searched to identify studies that utilized advanced proteomic platforms (MS based) and systems biology tools to unfold the mechanism(s) behind ND in an attempt to unveil the mysterious biological processes that occur postinjury. Various PTMs have been found to be common between TBI and AD, whereas no similarities have been found between TBI and PD. Phosphorylated tau protein, glycosylated amyloid precursor protein, and many other modifications appear to be common in both TBI and AD. PTMs, differential protein profiles, and altered biological pathways appear to have critical roles in ND processes by interfering with their pathological condition in a manner similar to TBI. Advancement in glycoproteomic studies pertaining to ND and TBI is urgently needed in order to develop better diagnostic tools, therapies, and more favorable prognoses.

Risk factors for multiple sclerosis and associations with anti-EBV antibody titers.

Multiple sclerosis (MS) is an inflammatory demyelination of the central nervous system. We investigated the prevalence of EBV seropositivity and other known risk factors for MS (age, smoking, low vitamin D) and their effect on anti-EBV antibody titers. We retrospectively studied 249 MS patients receiving care at the American University of Beirut Medical Center and 230 controls, during 2010-2014. EBV seropositivity was higher in MS patients compared to controls for both anti-VCA (99.5%; 97.2%) and anti-EBNA-1 (96.3%; 89.4%), and the titers were significantly higher in MS patients. MS patients had a significantly lower vitamin D level (15.5 ± 8.3 ng/ml) compared to controls (20.4 ± 11.3 ng/ml). The proportion of heavy smokers and overweight individuals was significantly higher in MS patients. Lebanese MS patients have risk factors similar to those in western countries. Older age and female gender were associated with a higher anti-VCA titer and male gender with a higher anti-EBNA-1.

Neuroproteomics and microRNAs studies in multiple sclerosis: transforming research and clinical knowledge in biomarker research.

Multiple sclerosis (MS) is a complex disease characterized by extensive phenotypic variability. Biomarkers to capture the different aspects of MS heterogeneity, and to help make a diagnosis and monitor disease progression, while providing insights into etiopathogenesis and response to treatment, are urgently needed. Omics technologies and research efforts with microRNAs have provide unparalleled opportunities for exploring altered protein profiles associated with molecular mechanisms of disease, substantially expanding the list of candidate biomarkers for MS. This review presents evidence from proteomic studies that have focused on identification of biomarkers released in biofluids as a result of the different pathophysiological processes of MS. Also discussed is the emerging role of miRNAs as complementary biomarkers related to cellular processes occurring in MS patients. Also provided is an overview of candidate biomarkers that have been proposed for elucidating pathophysiological processes and disease activity and for guiding clinical diagnosis and/or therapeutic interventions in MS.

Incorporating gerontological content in the nursing curriculum. The case of AUB School of Nursing.

In Lebanon, the proportion of older adults (over 65 years) is on the rise. This rise is associated with increased morbidity rates and the need for age-specific medical and nursing care. The number of nurses specializing in geriatric care remains very small despite the increased need for this specialty. The nursing curriculum at the Hariri School of Nursing at the American University of Beirut (AUB) has integrated gerontological content in both undergraduate and graduate programs as an essential step to prepare future nurses for the care of the growing population of older adults and consequently to support the health care system. In line with the essential competencies proposed by the American Association of Colleges of Nursing (AACN), the school of nursing at AUB is preparing entry level and advanced practice nurses to care for the geriatric population. Furthermore, developing specialists in the field of gerontology and launching an interdisciplinary graduate program on 'Care of the Older Adult' is more and more becoming a desired development for the future.

Simvastatin and environmental enrichment effect on recognition and temporal order memory after mild-to-moderate traumatic brain injury.

PRIMARY OBJECTIVE: The purpose of this study was to investigate the effect of mild-to- moderate (m-mod) traumatic brain injury (TBI) on spontaneous object (SO) recognition and temporal order (TO) memory in male Wistar rats and to compare the effects of environmental enrichment (EE) and simvastatin (Sim) on SO and TO memory post-injury. RESEARCH DESIGN: A randomized repeated measure experimental design was used. METHODS AND PROCEDURE: Seven days after arrival, animals received the injury or sham surgery. Using a Y-shaped maze, SO and TO memory was assessed in the two groups of animals at 6, 24, 48, 72 hours and 7, 14, 21 and 35 days post-surgery. Total time exploring each object and discrimination ratio were calculated and analysed. Then SO and TO memory were compared between two groups that received either Sim or EE for 2 hours daily starting 24 hours post-injury and a sham group that received saline for 14 days post-injury. RESULTS: The results showed that the injury impaired SO and TO memory compared to the sham up to 35 days post-trauma. Injured animals exhibited familiarity preference, novelty aversion and impaired TO performance. EE improved the animals' SO recognition deficits 7 days post-injury after a shorter delay (1 minute) only and Sim reversed TO memory deficits 14 days post-injury after a longer delay (60 minutes). CONCLUSION: Persistent SO and TO memory deficits follow TBI in animals; Simv and EE seem to be promising therapies of TBI memory deficits.

Psychometric validation of the Arabic multiple sclerosis resiliency scale: Uncovering resilience factors in Lebanese MS patients for clinical and research advancements.

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that involves the central nervous system (CNS). Individuals with Multiple Sclerosis (MS) may experience difficulty adapting to their diagnosis as the unpredictable nature of the disease can be challenging to cope with. Methods: The purpose of this study is twofold. First, we have culturally adapted and analyzed the Arabic version of the Multiple Sclerosis Resiliency Scale (MSRS) psychometric properties. Second, we aimed to explore resilience in a sample of Lebanese patients with MS in the face of the chronic disease and financial hardship that Lebanon is going through to evaluate their strengths and struggles. The sample consisted of 306 participants aged between 18 and 79 diagnosed with MS for at least one year. Results: After examining criterion validity, construct validity, internal consistency, and test-retest reliability, the Arabic version of the MSRS exhibited good psychometric properties. The study also revealed that resilience increases with age and lower disability scores. Additionally, individuals with higher resilience levels displayed lower levels of depression. The research revealed that MS patients have high resilience, mainly relying on cognitive and emotional strategies, social support from family and friends, MS peer support, and spirituality. Conclusion: These findings highlight the importance of emotional coping strategies and social support in building resilience among MS patients.

Health-related quality of life and utilities among Lebanese patients with Multiple Sclerosis: A cross-sectional study.

OBJECTIVE: This study assessed the Health-Related Quality of Life (HRQoL) and utilities of Multiple Sclerosis (MS) patients in Lebanon using generic and MS-specific QoL instruments, categorized by disease severity, and explored factors associated with HRQoL. METHODS: This was a cross-sectional, retrospective HRQoL study collecting data through face-to-face interviews using the EQ-5D-5 L and the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaires. We enrolled Lebanese patients aged ≥18 years, diagnosed with MS for >6 months. Patients were categorized by disease severity using the expanded disability status scale (EDSS) scores: 0-3 (mild MS), 4-6.5 (moderate MS), and 7-9 (severe MS). Bivariate and linear regression analyses were performed to study factors associated with HRQoL. RESULTS: A total of 210 patients (mean age: 43.3 years; 65.7 % females) were included. The mean EQ-5D-5 L utility score was 0.74. This score decreased significantly with disease severity (p < 0.001 for the trend): 0.93, 0.60, and 0.32 for mild, moderate, and severe MS, respectively. The mean MusiQoL global index score was 71.33 and was significantly lower for severe MS (58.68), than for moderate (65.23) and mild (77.80), (p < 0.001 for the trend). Higher educational level, lower EDSS scores, and longer disease duration were associated significantly with a higher EQ-5D-5 L utility (R2 = 0.67), while employment, lower EDSS scores, and decrease in cognitive difficulties were associated with better MusiQoL utility (R2 = 0.46). CONCLUSIONS: This study reveals a significant and gradual deterioration in HRQoL as MS progresses, resulting in low utility scores for patients with severe MS.

Resilience, mental health, sleep, and smoking mediate pathways between lifetime stressors and Multiple Sclerosis severity.

Intro: Lifetime stressors (e.g., poverty, violence, discrimination) have been linked to Multiple Sclerosis (MS) features; yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom evaluated. Aim: To deconstruct pathways between lifetime stressors and cumulative severity on MS outcomes, accounting for resilience. Methods: Adults with MS (N=924) participated in an online survey through the National MS Society listserv. Structural Equation Modeling was used to examine the direct and indirect effect of lifetime stressors (count/severity) on MS severity (self-reported disability, relapse burden, fatigue, pain intensity and interference), via resilience, mental health (anxiety and depression), sleep disturbance, and smoking. Results: The final analytic model had excellent fit (GFI=0.998). Lifetime stressors had a direct relationship with MS severity (ß=0.27, p<.001). Resilience, mental health, sleep disturbance, and smoking significantly mediated the relationship between lifetime stressors and MS severity. The total effect of mediation was significant (ß=0.45). Conclusions: This work provides foundational evidence to inform conceptualization of pathways by which stress could influence MS disease burden. Resilience may attenuate effects of stressors, while poor mental health, smoking, and sleep disturbances may exacerbate their impact. Parallel with usual care, these mediators could be targets for early multimodal therapies to improve disease course.

Validation of the Cognitive Reserve Index Questionnaire (CRIq) in Arabic.

Cognitive reserve is the adaptability of cognitive processes in the face of brain aging and pathology. This study aimed to validate the Arabic version of the Cognitive Reserve Index Questionnaire (CRIq) in a healthy Lebanese sample. CRIq assesses cognitive reserve through three domains: education, working activity, and leisure time. Statistical measures, including descriptive and regression analysis along with structural equation modeling, were utilized to investigate the convergent and discriminant validity of the CRIq, incorporating fluid intelligence (Gf) and measures of cognitive function, long-term memory encoding and retrieval (Glr), and processing speed (Gs). Results from 174 participants revealed that the activities assessed by the CRIq-Arabic were comparable to the original CRIq study, with slight cultural differences. The internal consistency of the CRIq-Arabic was good (Cronbach's α = 0.88), indicating reliability. Convergent validity was confirmed, with moderate to high loadings on the cognitive reserve latent construct. Discriminant validity was supported as correlations between cognitive reserve variables and non-target constructs (Gf, Glr, and Gs) were less than 1. The findings provide an initial psychometric validation of the CRIq-Arabic. Further research of clinical samples is needed to enhance its utility in neuropsychological practice.

The societal costs of multiple sclerosis in Lebanon: a cross-sectional study.

INTRODUCTION: This study assessed the societal costs of multiple sclerosis (MS) in Lebanon, categorized by disease severity. METHODS: This was a cross-sectional, prevalence-based, bottom-up study using a face-to-face questionnaire. Patients were stratified by disease severity using the expanded disability status scale (EDSS); EDSS scores of 0-3, 4-6.5, and 7-9 indicating respectively mild, moderate, and severe MS. All direct medical, nonmedical, and indirect costs related to reduced productivity were accounted for regardless of who bore them. Costs, collected from various sources, were presented in international US dollars (US$) using the purchasing power parity (PPP) conversion rate. RESULTS: We included 210 Lebanese patients (mean age: 43.3 years; 65.7% females). The total annual costs per patient were PPP US$ 33,117 for 2021, 12.4 times higher than the nominal GDP per capita. Direct costs represented 52% (US$ 17,185), direct nonmedical costs 8% (US$ 2,722), and indirect costs 40% (US$ 13, 211) of the mean annual costs. The total annual costs per patient increased with disease severity and were PPP US$ 29,979, PPP US$ 36,125, PPP US$ 39,136 for mild, moderate, and severe MS, respectively. CONCLUSION: This study reveals the huge economic burden of MS on the Lebanese healthcare system and society.

Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden.

BACKGROUND: Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function. METHODS: Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3) 42 I.U./Kg for 21 days. Control animals received equal volume of normal saline. Behavioral testing in water maze and spontaneous object recognition tasks started on day 14. Levels of interleukin (IL)-1ß and IL-10 were quantified to assess inflammatory state. Also, beta amyloid (Aß) clearance and Aß load were measured. RESULTS: Our results show that: (1) aged rats demonstrated significant learning and memory impairment overall compared to younger animals. However, the age-related decline in learning and memory was ameliorated by the supplementation of vitamin D. No vitamin D effect on learning and memory was seen in the young animals; 2) the pro-inflammatory cytokine IL-1ß is significantly increased while the anti-inflammatory cytokine IL-10 is significantly decreased in the aged rats compared to the young animals; but this age-related change in inflammatory state was mitigated by vitamin D supplementation. No effects of vitamin D were seen on the IL-1ß and IL-10 expression in the young rats; (3) vitamin D increased Aß clearance and decreased amyloid burden in the aged rats while no significant difference was seen between the young animal groups. CONCLUSIONS: Our data suggest that vitamin D supplementation modulated age-related increase in pro-inflammatory state and amyloid burden. It is possible that these effects of vitamin D mediated the decrease memory impairment seen in the aged rats making it a useful therapeutic option to alleviate the effects of aging on cognitive function.

Mild traumatic brain injury (MTBI) leads to spatial learning deficits.

PRIMARY OBJECTIVE: The aim of this study was to investigate the effect of mild and severe TBI on young male Wistar rats' spatial learning. RESEARCH DESIGN: Randomized repeated measure experimental design was used to examine spatial learning in three independent animal groups. METHODS AND PROCEDURES: Twenty-four (severe n = 9, mild n = 8, sham n = 7) male rats were included in the study. Animals received controlled mild (1.5 mm), severe (2.5 mm) cortical impact injury or sham surgery. Spatial learning was assessed daily using a modified Morris water maze test, 20 days post-trauma, for 5 consecutive days. Percentage time travelled within each quadrant and escape latency were calculated. All animals' hippocampal brain regions were examined post-injury using neuron (MAP2) and pre-synaptic protein (Synaptophysin) biomarkers. MAIN OUTCOMES AND RESULTS: It took the animals with mild injury until day 3 to reach the platform; and animals with mild and severe injury spent significantly less time in the target quadrant than the sham. The hippocampal neuron numbers differed proportionately between animals with severe and mild injury, but the percentage of synaptophysin density was significantly less in the dentate gyrus of both animals with mild and severe injury than sham group. CONCLUSION: Persistent spatial learning deficits exist after mild TBI; these deficits appear equivalent to deficits exhibited after a more severe injury.