Potential Biomarkers of impulsivity in mild traumatic brain injury: A pilot study.

Very few studies have investigated cognition and impulsivity following mild traumatic brain injury (mTBI) in the general population. Furthermore, the neurobiological mechanisms underlying post-TBI neurobehavioral syndromes are complex and remain to be fully clarified. Herein, we took advantage of machine learning based-modeling to investigate potential biomarkers of mTBI-associated impulsivity. Twenty-one mTBI patients were assessed within one-month post-TBI and their data were compared to 19 healthy controls on measures of impulsivity (Barratt Impulsiveness Scale - BIS), executive functioning, episodic memory, self-report cognitive failures and blood biomarkers of inflammation, vascular and neuronal damage. mTBI patients were significantly more impulsive than controls in BIS total and subscales. Serum levels of sCD40L, Cathepsin D, IL-4, Neuropilin-1, IFN-α2, and Copeptin were associated with impulsivity in mTBI patients. Besides showing that mTBI are associated with impulsivity in non-military people, we unveiled different pathophysiological pathways potentially implicated in mTBI-related impulsivity.

The potential role of renin-angiotensin system in mild traumatic brain injury.

Traumatic brain injury (TBI) is a serious public health problem, affecting 69 million people worldwide annually. Mild TBI (mTBI) comprises the majority of the cases and remains the most neglected TBI severity. Its intricate pathophysiology involves complex cellular and molecular processes that remain uncomprehended. Although the renin-angiotensin system (RAS) has its well-known roles in blood pressure regulation and fluid balance, accumulating evidence demonstrates its active expression and signaling in the central nervous system. Over the past years, pre-clinical studies have been supporting the role of RAS in mTBI. However, particularly for human TBI, evidence is still missing. Herein, we investigated peripheral levels of angiotensin II (Ang II) and angiotensin-converting enzyme (ACE), components of RAS classical axis, as well as angiotensin-(1-7) [Ang-(1-7)] and ACE2, components of RAS counter-regulatory axis, in 28 mTBI patients and 24 healthy controls. In the first 24 h, mTBI patients displayed lower ACE (p = 0.0004) and ACE2 (p = 0.0047) concentrations and an increase in Ang II (p = 0.0234) and Ang-(1-7) (p = 0.0225) levels compared to controls. Interestingly, at 30 days follow-up, mTBI patients increased the levels of ACE (p = 0.0415) and ACE2 (p = 0.0416) along with a decrease in Ang II (p = 0.0039) and Ang-(1-7) (p = 0.0015) concentrations compared with their measures at 24 h after TBI. Also, our receiver operating curve (ROC) analysis demonstrated that ACE concentration was a good predictor of mTBI diagnosis (AUC = 0.798, p < 0.0001). The current study provides the first clinical evidence of RAS molecule's involvement in mTBI and their possible role as discriminating biomarkers.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI's long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

Traumatic brain injury biomarkers in pediatric patients: a systematic review.

Traumatic brain injury (TBI) is the main cause of pediatric trauma death and disability worldwide. Recent studies have sought to identify biomarkers of TBI for the purpose of assessing functional outcomes. The aim of this systematic review was to evaluate the utility of TBI biomarkers in the pediatric population by summarizing recent findings in the medical literature. A total of 303 articles were retrieved from our search. An initial screening to remove duplicate studies yielded 162 articles. After excluding all articles that did not meet the inclusion criteria, 56 studies were gathered. Among the 56 studies, 36 analyzed serum biomarkers; 11, neuroimaging biomarkers; and 9, cerebrospinal fluid (CSF) biomarkers. Most studies assessed biomarkers in the serum, reflecting the feasibility of obtaining blood samples compared to obtaining CSF or performing neuroimaging. S100B was the most studied serum biomarker in TBI, followed by SNE and UCH-L1, whereas in CSF analysis, there was no unanimity. Among the different neuroimaging techniques employed, diffusion tensor imaging (DTI) was the most common, seemingly holding diagnostic power in the pediatric TBI clinical setting. The number of cross-sectional studies was similar to the number of longitudinal studies. Our data suggest that S100B measurement has high sensitivity and great promise in diagnosing pediatric TBI, ideally when associated with head CT examination and clinical decision protocols. Further large-scale longitudinal studies addressing TBI biomarkers in children are required to establish more accurate diagnostic protocols and prognostic tools.

Role of cytokine and neurotrophic factors in nicotine addiction in the conditioned place preference paradigm.

The mechanisms involved in the maintenance of cigarette smoking and nicotine reward remain unclear. Immune response might play an important role in this context. Nicotine may induce both central and systemic inflammatory responses as well as changes in the regulation of brain-derived neurotrophic factor (BDNF). The conditioned place preference (CPP) is a method used for the evaluation of nicotine-induced reward, reproducing nicotine-seeking behavior in humans. So far, there are no studies investigating the relationship between neuroinflammation and nicotine-induced CPP. This study aimed to evaluate the levels of inflammatory mediators and neurotrophic factors in key areas of the central nervous system (CNS) of mice subject to nicotine-induced CPP. CPP was induced with an intraperitoneal administration of 0.5 mg/kg of nicotine in male Swiss mice, using an unbiased protocol. Control group received vehicle by the same route. The levels of cytokines, chemokines, and neurotrophic factors were measured using Enzyme-Linked Immunosorbent Assay (ELISA) in the brain after CPP test. As expected, nicotine induced place preference behavior. In parallel, we observed increased peripheral levels of IL-6 and IL-10 alongside increased hippocampal levels of NGF but decreased GDNF in mice treated with nicotine compared to controls. In the striatum, nicotine promoted decrease of IL-1ß, IL-10 and GDNF levels, while the levels of all the mediators were similar between groups in the pre-frontal cortex. Our results provide evidence on the role of cytokines and neurotrophic factors in nicotine-induced CPP in mice.

Is there any association between Toxoplasma gondii infection and bipolar disorder? A systematic review and meta-analysis.

BACKGROUND: The relationship between Toxoplasma gondii infection and the development of bipolar disorder (BD) has long been investigated, yet to date it is still poorly understood and documented. The aim of this review is to derive a summary estimate of the strength of the association between infection with T. gondii and BD from the available published studies. METHODS: A systematic review was performed using PubMed, LILACS, PsycINFO, and Embase databases. Studies which included a proportion of seropositive BD patients and controls were further examined in a meta-analysis. RESULTS: One hundred eighteen citations were initially retrieved. Thirteen studies were included in our systematic review. Eight out of these thirteen studies were included in our meta-analysis. Statistical analyses showed that T. gondii infection is associated with with BD (OR=1.26). LIMITATIONS: Small sample size was the major limitation among the studies that carried out serological analyses. In addition, the available studies did not have enough information on disease status/severity or type of bipolar disorder. Also, it was not possible to analyze pregnancy status or perinatal infection. Future studies addressing the aforementioned topics are clearly needed. CONCLUSIONS: Despite heterogeneous results, patients with BD are more likely to be infected by T. gondii than controls. Early T. gondii infection might predispose the development of BD. T.gondii infection is becoming clinically relevant in psychiatric disorders and future mechanistic studies are required to elucidate the underlying pathophysiological mechanisms.