Nigrostriatal Inflammation Is Associated with Nonmotor Symptoms in an Experimental Model of Prodromal Parkinson's Disease.

Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. The current study aimed to characterize the behavioral and cognitive changes in a toxin-induced model of prodromal PD-like syndrome. We also sought to investigate the role of neuroinflammation in prodromal PD-related NMS. Male mice were subjected to bilateral intranasal infusion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline (control group), followed by comprehensive behavioral, pathological and neurochemical analysis. Intranasal MPTP infusion was able to cause the loss of dopaminergic neurons in the substantia nigra (SN). In parallel, it induced impairment in olfactory discrimination and social memory consolidation, compulsive and anxiety-like behaviors, but did not influence motor performance. Iba-1 and GFAP expressions were increased in the SN, suggesting an activated state of microglia and astrocytes. Consistent with this, MPTP mice had increased levels of IL-10 and IL-17A, and decreased levels of BDNF and TrkA mRNA in the SN. The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD.

siRNA lipid nanoparticles for CXCL12 silencing modulate brain immune response during Zika infection.

CXCL12 is a key chemokine implicated in neuroinflammation, particularly during Zika virus (ZIKV) infection. Specifically, CXCL12 is upregulated in circulating cells of ZIKV infected patients. Here, we developed a lipid nanoparticle (LNP) to deliver siRNA in vivo to assess the impact of CXCL12 silencing in the context of ZIKV infection. The biodistribution of the LNP was assessed in vivo after intravenous injection using fluorescently tagged siRNA. Next, we investigated the ability of the developed LNP to silence CXCL12 in vivo and assessed the resulting effects in a murine model of ZIKV infection. The LNP encapsulating siRNA significantly inhibited CXCL12 levels in the spleen and induced microglial activation in the brain during ZIKV infection. This activation was evidenced by the enhanced expression of iNOS, TNF-α, and CD206 within microglial cells. Moreover, T cell subsets exhibited reduced secretion of IFN-É£ and IL-17 following LNP treatment. Despite no observable alteration in viral load, CXCL12 silencing led to a significant reduction in type-I interferon production compared to both ZIKV-infected and uninfected groups. Furthermore, we found grip strength deficits in the group treated with siRNA-LNP compared to the other groups. Our data suggest a correlation between the upregulated pro-inflammatory cytokines and the observed decrease in strength. Collectively, our results provide evidence that CXCL12 silencing exerts a regulatory influence on the immune response in the brain during ZIKV infection. In addition, the modulation of T-cell activation following CXCL12 silencing provides valuable insights into potential protective mechanisms against ZIKV, offering novel perspectives for combating this infection.

Behavioral, neurochemical and neuroimmune features of RasGEF1b deficient mice.

The factor RasGEF1b is a Ras guanine exchange factor involved in immune responses. Studies have also implicated RasGEF1b in the CNS development. It is still limited the understanding of the role of RasGEF1b in CNS functioning. Using RasGEF1b deficient mice (RasGEF1b-cKO), we investigated the impact of this gene deletion in behavior, cognition, brain neurochemistry and microglia morphology. We showed that RasGEF1b-cKO mice display spontaneous hyperlocomotion and anhedonia. RasGEF1b-cKO mice also exhibited compulsive-like behavior that was restored after acute treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (5 mg/kg). A down-regulation of mRNA of dopamine receptor (Drd1, Drd2, Drd4 and Drd5) and serotonin receptor genes (5Htr1a, 5Htr1b and 5Htr1d) was observed in hippocampus of RasGEF1b-cKO mice. These mice also had reduction of Drd1 and Drd2 in prefrontal cortex and 5Htr1d in striatum. In addition, morphological alterations were observed in RasGEF1b deficient microglia along with decreased levels of hippocampal BDNF. We provided original evidence that the deletion of RasGEF1b leads to unique behavioral features, implicating this factor in CNS functioning.

Impact of Strength Training Intensity on Brain-derived Neurotrophic Factor.

The present study employed a randomized crossover design to investigate the effect of strength-training exercise at varying intensities on acute changes in plasma brain-derived neurotrophic factor (BDNF) levels. Fourteen trained male subjects (41.0±5.8 years old) were enrolled in the current study. The strength-training protocol included bench press, leg press, and lat pull-down exercises. Participants performed four sets with repetition failure at 60% or 80% of their one-repetition maximum (1RM), with a two-minute rest period. The order of intensity was randomized among volunteers. Blood samples were collected before, immediately after, and one hour after each exercise protocol. A time-point comparison revealed that a single session of strength training at 60% of 1RM increased lactate plasma concentrations from 1.2 to 16 mmol/L (p<0.0001). However, no significant changes were observed in the plasma BDNF concentration. Conversely, the training session at 80% of 1RM increased lactate concentrations from 1.3 to 14 mmol/L (p<0.0001) and BDNF concentrations from 461 to 1730 pg/ml (p=0.035) one hour after the session's conclusion. These findings support the hypothesis that a single strength-training session at 80% 1RM can significantly enhance circulating levels of BDNF.

Targeting the Renin-Angiotensin System (RAS) for Neuropsychiatric Disorders.

BACKGROUND: Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic targets. AIMS: We aim to report current experimental and clinical evidence on the role of RAS in physiology and pathophysiology of mood disorders, schizophrenia, AD and related dementias. We also aim to discuss bottlenecks and future perspectives that can foster the development of new related therapeutic strategies. CONCLUSION: The available evidence supports positive therapeutic effects for neuropsychiatric disorders with the inhibition/antagonism of the ACE/Ang II/AT1 receptor axis or the activation of the ACE2/Ang-(1-7)/Mas receptor axis. Most of this evidence comes from pre-clinical studies and clinical studies lag much behind, hampering a potential translation into clinical practice.

Effect of the COVID-19 Pandemic on the Epidemiology of Pediatric Traumatic Brain Injury in Brazil.

Aim In response to the coronavirus 2019 disease (COVID-19) pandemic, governments worldwide implemented measures to prevent infection, resulting in restricted school activities, restricted children's freedom of movement, and increased risk of violence and injuries at home, including traumatic brain injury (TBI), among children. In Brazil, the consequences of the COVID-19 pandemic on the causes, severity, and mortality of pediatric TBI have not yet been investigated. Thus, our study aimed to determine whether the COVID-19 pandemic has affected the epidemiology of pediatric TBI among Brazilian children. Materials and methods We investigated the patients with TBI aged <18 years who visited a tertiary trauma center in Brazil in 2019 and 2020. TBI-related variables, such as classification, mechanism, clinical manifestations, need for intervention, morbidity, and mortality, were recorded. Furthermore, we used a nationwide databank to collect information on mortality from external causes of trauma and violence in the pediatric population in 2019 and 2020. The Mann-Whitney test was used to compare quantitative variables related to the mechanisms and severity of TBI in both periods in order to determine the impact of the COVID-19 pandemic. Results Of the patients with traumatic brain injury, 1371 visited the trauma center in 2019 and 1052 in 2020. No difference was noted in the incidence rate of abusive head trauma between these periods (p=0.142) or in mortality from violence in Brazil. Recreational causes of pediatric TBI increased during the first year of the COVID-19 pandemic in Brazil and falls from bicycles significantly increased during the pandemic (p<0.001). Conclusion A global reduction in pediatric admissions to emergency rooms as well as no impact on mortality and severity of pediatric TBI were observed during the COVID-19 pandemic in Brazil. Additionally, a public education program regarding child safety during recreational activities, particularly how to avoid falls from bicycles was recommended.

Weight-drop model as a valuable tool to study potential neurobiological processes underlying behavioral and cognitive changes secondary to mild traumatic brain injury.

The pathophysiology of post-traumatic brain injury (TBI) behavioral and cognitive changes is not fully understood, especially in its mild presentation. We designed a weight drop TBI model in mice to investigate the role of neuroinflammation in behavioral and cognitive sequelae following mild TBI. C57BL/6 mice displayed depressive-like behavior at 72 h after mild TBI compared with controls, as indicated by a decrease in the latency to first immobility and climbing time in the forced swim test. Additionally, anxiety-like behavior and hippocampal-associated spatial learning and memory impairment were found in the elevated plus maze and in the Barnes maze, respectively. Levels of a set of inflammatory mediators and neurotrophic factors were analyzed at 6 h, 24 h, 72 h, and 30 days after injury in ipsilateral and contralateral hemispheres of the prefrontal cortex and hippocampus. Principal components analysis revealed two principal components (PC), which represented 59.1% of data variability. PC1 (cytokines and chemokines) expression varied between both hemispheres, while PC2 (neurotrophic factors) expression varied only across the investigated brain areas. Our model reproduces mild TBI-associated clinical signs and pathological features and might be a valuable tool to broaden the knowledge regarding mild TBI pathophysiology as well as to test potential therapeutic targets.

A suitable model to investigate acute neurological consequences of coronavirus infection.

OBJECTIVE AND DESIGN: The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model. MATERIAL: Wild-type C57BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3). METHODS: Mice underwent behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, ELISA, histopathological, immunohistochemical and synaptosome analysis. RESULTS: Increased viral titers and mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, which is indicative of excitotoxicity, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain. Finally, behavioral analysis showed impaired motor, anhedonia-like and anxiety-like behaviors in animals infected with MHV-3. CONCLUSIONS: In conclusion, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.

Chronic hyperpalatable diet induces impairment of hippocampal-dependent memories and alters glutamatergic and fractalkine axis signaling.

Chronic consumption of hyperpalatable and hypercaloric foods has been pointed out as a factor associated with cognitive decline and memory impairment in obesity. In this context, the integration between peripheral and central inflammation may play a significant role in the negative effects of an obesogenic environment on memory. However, little is known about how obesity-related peripheral inflammation affects specific neurotransmission systems involved with memory regulation. Here, we test the hypothesis that chronic exposure to a highly palatable diet may cause neuroinflammation, glutamatergic dysfunction, and memory impairment. For that, we exposed C57BL/6J mice to a high sugar and butter diet (HSB) for 12 weeks, and we investigated its effects on behavior, glial reactivity, blood-brain barrier permeability, pro-inflammatory features, glutamatergic alterations, plasticity, and fractalkine-CX3CR1 axis. Our results revealed that HSB diet induced a decrease in memory reconsolidation and extinction, as well as an increase in hippocampal glutamate levels. Although our data indicated a peripheral pro-inflammatory profile, we did not observe hippocampal neuroinflammatory features. Furthermore, we also observed that the HSB diet increased hippocampal fractalkine levels, a key chemokine associated with neuroprotection and inflammatory regulation. Then, we hypothesized that the elevation on glutamate levels may saturate synaptic communication, partially limiting plasticity, whereas fractalkine levels increase as a strategy to decrease glutamatergic damage.

Innate and adaptive immune gene expression in the brain is associated with neuropathological changes after infection with bovine alpha-herpesvirus-5 in mice.

Bovine alpha herpesvirus-5 (BoAHV-5) is related to the development of meningoencephalitis in cattle. Very little is known about the molecular pathways involved in the central nervous system (CNS) damage associated with inflammation during BoHV-5 infection in mice. To better identify the specific immunological pathways triggered by BoAHV-5 infection in mice, we evaluated the mRNA expression of 84 genes involved in innate and adaptive immune responses. We compared gene expression changes in the cerebrum from noninfected and infected mice with BoHV-5 at a 1 × 107 TCID50. Then, we analyzed the association of these genes with neurological signs, neuropathology, and activation of glial cells in response to BoHV-5 infection. Three days after BoAHV-5 infection, increased expression of TNF, IL-2, CXCL10, CXCR3, CCR4, CCL5, IFN-γ, IL-10, IRF7, STAT1, MX1, GATA 3 C3, LIZ2, caspase-1 and IL-1b was found. We also observed the upregulated expression of the CD8a, TBX21 and CD40LG genes and the downregulated expression of the CD4 gene after BoAHV-5 infection. In addition, BoHV-5-infected animals showed higher levels of all the evaluated inflammatory mediators (TNF, IFN-γ and IL-10) on day 3 postinfection. BoAHV-5-infected animals showed neurological changes along with meningoencephalitis, neuropil vacuolation, hemorrhage and reactive gliosis. Astrogliosis and microgliosis, indicated by increased expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), were found throughout the neuropil in infected brains. Moreover, cleaved caspase-3 immunopositive glio-inflammatory cells were visualized around some blood vessels in areas of neuroinflammation in the cerebrum. In agreement on that we found higher cleaved caspase-3 and Iba-1 expression evaluated by western blot analysis in the brains of infected mice compared to control mice. In conclusion, our results revealed.

Chronic infection by atypical Toxoplasma gondii strain induces disturbance in microglia population and altered behaviour in mice.

Toxoplasma gondii chronic infection is characterized by the establishment of tissue cysts in the brain and increased levels of IFN-γ, which can lead to brain circuitry interference and consequently abnormal behaviour in mice. In this sense, the study presented here sought to investigate the impact of chronic infection by two T. gondii strains in the brain of infection-resistant mice, as a model for studying the involvement of chronic neuroinflammation with the development of behavioural alterations. For that, male BALB/c mice were divided into three groups: non-infected (Ni), infected with T. gondii ME49 clonal strain (ME49), and infected with TgCkBrRN2 atypical strain (CK2). Mice were monitored for 60 days to establish the chronic infection and then submitted to behavioural assessment. The enzyme-linked immunosorbent assay was used for measurement of specific IgG in the blood and levels of inflammatory cytokines and neurotrophic factors in the brain, and the cell's immunophenotype was determined by multiparametric flow cytometry. Mice infected with ME49 clonal strain displayed hyperlocomotor activity and memory deficit, although no signs of depressive- and/or anxiety-like behaviour were detected; on the other hand, chronic infection with CK2 atypical strain induced anxiety- and depressive-like behaviour. During chronic infection by CK2 atypical strain, mice displayed a higher number of T. gondii brain tissue cysts and inflammatory infiltrate, composed mainly of CD3+ T lymphocytes and Ly6Chi inflammatory monocytes, compared to mice infected with the ME49 clonal strain. Infected mice presented a marked decrease of microglia population compared to non-infected group. Chronic infection with CK2 strain produced elevated levels of IFN-γ and TNF-ɑ in the brain, decreased NGF levels in the prefrontal cortex and striatum, and altered levels of fractalkine (CX3CL1) in the prefrontal cortex and hippocampus. The persistent inflammation and the disturbance in the cerebral homeostasis may contribute to altered behaviour in mice, as the levels of IFN-γ were shown to be correlated with the behavioural parameters assessed here. Considering the high incidence and life-long persistence of T. gondii infection, this approach can be considered a suitable model for studying the impact of chronic infections in the brain and how it impacts in behavioural responses.

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.

Inflammasome activation and assembly in Huntington's disease.

Huntington's disease (HD) is a rare neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. Inflammasomes are multiprotein complexes capable of sensing pathogen-associated and damage-associated molecular patterns, triggering innate immune pathways. Activation of inflammasomes results in a pro-inflammatory cascade involving, among other molecules, caspases and interleukins. NLRP3 (nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3) is the most studied inflammasome complex, and its activation results in caspase-1 mediated cleavage of the pro-interleukins IL-1ß and IL-18 into their mature forms, also inducing a gasdermin D mediated form of pro-inflammatory cell death, i.e. pyroptosis. Accumulating evidence has implicated NLRP3 inflammasome complex in neurodegenerative diseases. The evidence in HD is still scant and mostly derived from pre-clinical studies. This review aims to present the available evidence on NLRP3 inflammasome activation in HD and to discuss whether targeting this innate immune system complex might be a promising therapeutic strategy to alleviate its symptoms.

Modified Levels of Renin Angiotensin Related Components in the Frontal Cortex and Hippocampus were Associated with Neuroinflammation and Lower Neuroprotective Effects of NGF During Acute Hepatic Encephalopathy in Mice.

BACKGROUND: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that involves cognitive and motor dysfunctions due to hepatic failure. The clinical and experimental studies suggest that the angiotensin (Ang) converting enzyme (ACE), Ang II, and angiotensin type 1 receptor (AT1R), which compose the classical pathway of the renin-angiotensin system (RAS), exacerbate neuroinflammation in different neurologic diseases. Conversely, Ang-(1-7), ACE2, and Mas receptor, which integrate the alternative RAS axis, have been shown as promising therapeutic targets in neuropsychiatric disorders, leading to neuroprotection. OBJECTIVE: This study aimed to investigate the potential participation of the RAS components in thioacetamide (TAA)-induced HE in mice. METHODS: We also evaluated the levels of neurotrophic factors, pro-inflammatory cytokines, and chemokine in the central nervous system of TAA-induced HE in mice. Mice were submitted to acute liver failure induced by TAA administration by intraperitoneal route. Measurements of RAS components (ACE, Ang II, ACE2 and Ang1-7) and neurotrophic factors (BDNF, GDNF and NGF) were obtained by ELISA assay. Pro-inflammatory cytokines (TNF, IFN-γ, IL-6, IL-12p70) and the chemokine (CCL2) were quantified by cytometric bead array. The student's t-test was applied for statistical analysis. RESULTS: Mice presented increased cortical levels of ACE, while Ang-(1-7) levels were decreased in cortical and hippocampal samples compared to controls. Moreover, HE mice had an increase in the Ang II/Ang-(1-7) ratio along with reduced levels of neural growth factor (NGF) in the prefrontal cortex. They also showed elevated levels of IFN-γ and CCL2 in the prefrontal cortex and of TNF, IL-6, IL-12, and CCL2 in the hippocampus compared with controls. CONCLUSION: This study suggested that the reduction of components of the alternative RAS axis was associated with the deleterious effects of neuroinflammation and lower neuroprotective effects of NGF during TAA-induced HE.

Renin-Angiotensin System in Huntington's Disease: Evidence from Animal Models and Human Patients.

The Renin-Angiotensin System (RAS) is expressed in the central nervous system and has important functions that go beyond blood pressure regulation. Clinical and experimental studies have suggested that alterations in the brain RAS contribute to the development and progression of neurodegenerative diseases. However, there is limited information regarding the involvement of RAS components in Huntington's disease (HD). Herein, we used the HD murine model, (BACHD), as well as samples from patients with HD to investigate the role of both the classical and alternative axes of RAS in HD pathophysiology. BACHD mice displayed worse motor performance in different behavioral tests alongside a decrease in the levels and activity of the components of the RAS alternative axis ACE2, Ang-(1-7), and Mas receptors in the striatum, prefrontal cortex, and hippocampus. BACHD mice also displayed a significant increase in mRNA expression of the AT1 receptor, a component of the RAS classical arm, in these key brain regions. Moreover, patients with manifest HD presented higher plasma levels of Ang-(1-7). No significant changes were found in the levels of ACE, ACE2, and Ang II. Our findings provided the first evidence that an imbalance in the RAS classical and counter-regulatory arms may play a role in HD pathophysiology.

The Role of Neuroplasticity in Improving the Decision-Making Quality of Individuals With Agenesis of the Corpus Callosum: A Systematic Review.

Although individuals with agenesis of corpus callosum (ACC) possess intelligence coefficients within regular parameters, current studies have demonstrated decision-making compromise and potential negative social consequences. Furthermore, alternative pathways regarding brain connectivity in acallosal patients combined with cognitive therapy that would potentially mitigate such difficulties. Therefore, this study aimed to examine the current state of the art regarding brain foundations in the role of neuroplasticity by improving the decision-making quality in ACC. A systematic revision of literature was performed including studies conducted on non-syndromic ACC individuals and analyzing the impact of the potential role of neuroplasticity on the decision-making published to date. Studies with patients who underwent callosotomy were excluded. Experimental studies performed on animal models were included. During this period, 849 studies were identified; among them, 11 were eligible for qualitative analysis. Despite the paucity of evidence on this matter, patients with ACC present considerable decision-making difficulties mainly due to the functional connectivity impairment in the frontal lobes. Moreover, neuroplasticity was characterized by increased anterior commissure width as compared with controls. Notwithstanding, no studies were conducted on cognitive therapists managing this type of disease. Although the reorganization of inter-hemispheric bundles on anterior commissure has demonstrated the main natural neuroanatomic strategy in ACC, further evidence will be needed to clarify whether cognitive stimulus could improve the decision-making quality.

Traumatic brain injury in Brazil: an epidemiological study and systematic review of the literature.

BACKGROUND: Traumatic brain injury (TBI) is a serious public health problem worldwide. Although TBI is common in developing countries, there are few epidemiological studies. OBJECTIVE: To investigate the sociodemographic and clinical features of patients with TBI at the Hospital João XXIII, a public reference center for trauma in Belo Horizonte, Brazil, and to systematically review the available literature on TBI in Brazil. METHODS: Clinical and sociodemographic data were collected from electronic medical records for the entire month of July 2016. The literature on epidemiology of TBI in Brazil was systematically reviewed using MeSH/DeCS descriptors in the PubMed and Lilacs databases. RESULTS: Most patients admitted with TBI were male and under 60 years of age. Mild TBI was the most prevalent form and the most common cause of TBI was falls. A Glasgow Coma Scale score below 12, neuroimaging changes on computer tomography, and presence of any medical conditions were significantly associated with longer hospital stay. Brazilian studies showed that TBI affected mainly men and young adults. In addition, mild TBI was the most common TBI severity reported and the most common causes were motor vehicle accidents and falls. CONCLUSIONS: Overall, the profile of TBI in this center reflects the data from other Brazilian studies.

Traumatic brain injury in Brazil: an epidemiological study and systematic review of the literature / Traumatismo cranioencefálico no Brasil: um estudo epidemiológico e uma revisão sistemática da literatura

ABSTRACT Background: Traumatic brain injury (TBI) is a serious public health problem worldwide. Although TBI is common in developing countries, there are few epidemiological studies. Objective: To investigate the sociodemographic and clinical features of patients with TBI at the Hospital João XXIII, a public reference center for trauma in Belo Horizonte, Brazil, and to systematically review the available literature on TBI in Brazil. Methods: Clinical and sociodemographic data were collected from electronic medical records for the entire month of July 2016. The literature on epidemiology of TBI in Brazil was systematically reviewed using MeSH/DeCS descriptors in the PubMed and Lilacs databases. Results: Most patients admitted with TBI were male and under 60 years of age. Mild TBI was the most prevalent form and the most common cause of TBI was falls. A Glasgow Coma Scale score below 12, neuroimaging changes on computer tomography, and presence of any medical conditions were significantly associated with longer hospital stay. Brazilian studies showed that TBI affected mainly men and young adults. In addition, mild TBI was the most common TBI severity reported and the most common causes were motor vehicle accidents and falls. Conclusions: Overall, the profile of TBI in this center reflects the data from other Brazilian studies.

RESUMO Antecedentes: O traumatismo cranioencefálico (TCE) representa, mundialmente, um problema sério de saúde pública. Apesar de o TCE ser prevalente em países em desenvolvimento, estudos epidemiológicos permanecem escassos. Objetivo: Investigar as características sociodemográficas e clínicas de pacientes acometidos por TCE no Hospital João XXIII - centro de referência em trauma situado em Belo Horizonte, Brasil - e revisar sistematicamente toda a literatura disponível sobre o TCE no Brasil. Métodos: Os dados clínicos e sociodemográficos foram coletados apenas para o mês de julho, 2016, por meio de prontuários eletrônicos. A literatura sobre a epidemiologia do TCE no Brasil foi sistematicamente revisada usando descritores Medical Subject Headings (MeSH)/Descritores em Ciências da Saúde (DeCS) nos bancos de dados PubMed e Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs). Resultados: Os pacientes acometidos por TCE eram em sua maioria homens com menos de 60 anos. O TCE leve foi a gravidade mais prevalente entre os casos. O TCE foi causado principalmente por quedas. Escores menores que 12 na escala de Coma de Glasgow mais alterações de neuroimagem em tomografia computadorizada e a presença de qualquer comorbidade médica estão significativamente associados à maior estadia hospitalar. Estudos brasileiros demonstraram que o TCE acomete principalmente homens e adultos jovens. Além disso, o TCE leve foi a gravidade mais comum reportada, e os mecanismos de TCE mais comuns foram acidentes automobilísticos e quedas. Conclusões: O perfil de pacientes acometidos por TCE no centro de referência em questão reflete os dados de outros estudos brasileiros.

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.