Background Acute liver failure resulting from drug-induced liver injury can lead to the development of neurological complications called hepatic encephalopathy (HE). Hepatic transforming growth factor beta 1 (TGFβ1) is upregulated due to liver failure in mice and inhibiting circulating TGFβ reduced HE progression. However, the specific contributions of TGFβ1 on brain cell populations and neuroinflammation during HE are not known. Therefore, the aim of this study was to characterize hepatic and brain TGFβ1 signaling during acute liver failure and its contribution to HE progression using a combination of pharmacological and genetic approaches. Methods C57Bl/6 or neuron-specific transforming growth factor beta receptor 2 (TGFβR2) null mice (TGFβR2 ΔNeu ) were treated with azoxymethane (AOM) to induce acute liver failure and HE. The activity of circulating TGFβ1 was inhibited in C57Bl/6 mice via injection of a neutralizing antibody against TGFβ1 (anti-TGFβ1) prior to AOM injection. In all mouse treatment groups, liver damage, neuroinflammation, and neurological deficits were assessed. Inflammatory signaling between neurons and microglia were investigated in in vitro studies through the use of pharmacological inhibitors of TGFβ1 signaling in HT-22 and EOC-20 cells. Results TGFβ1 was expressed and upregulated in the liver following AOM injection. Pharmacological inhibition of TGFβ1 after AOM injection attenuated neurological decline, microglia activation, and neuroinflammation with no significant changes in liver damage. TGFβR2 ΔNeu mice administered AOM showed no effect on liver pathology but significantly reduced neurological decline compared to control mice. Microglia activation and neuroinflammation were attenuated in mice with pharmacological inhibition of TGFβ1 or in TGFβR2 ΔNeu mice. TGFβ1 increased chemokine ligand 2 (CCL2) and decreased C-X3-C motif ligand 1 (CX3CL1) expression in HT-22 cells and reduced interleukin-1 beta (IL-1ß) expression, tumor necrosis factor alpha (TNFα) expression, and phagocytosis activity in EOC-20 cells. Conclusion Increased circulating TGFβ1 following acute liver failure results in activation of neuronal TGFβR2 signaling, driving neuroinflammation and neurological decline during AOM-induced HE. Electronic supplementary material The online version of this article (10.1186/s12974-019-1455-y) contains supplementary material, which is available to authorized users.

Background Central nervous system (CNS) tumors pose a substantial health problem. Although data on specific time periods and regions of Africa have been previously reported, no study has yet to provide a systematic review of CNS tumors for the entire continent of Africa. This study aims to analyze the frequency of CNS tumors in Africa from 1960 to 2017. Methods A comprehensive literature search on CNS tumors in Africa was performed using multiple online scientific databases. The following keywords were queried in combination with the phrase “CNS tumors in Africa”: incidence, frequency, epidemiology, prevalence, brain, and cancer. A total of 26 articles met the inclusion criteria. Each selected article reported incidence and mortality rates from different regions of Africa in a time period between 1960 and 2017. SPSS21 statistical software was used to analyze the data. Results Nigeria, Egypt, and Uganda were found to have the most of the cases of CNS tumors in Africa. Males made up 54% of the 5902 cases per 100 000 population. The most common CNS tumors found were astrocytoma (24.70%), meningioma (22.22%), pituitary adenoma (8.4%), medulloblastoma (4.26%), craniopharyngioma (4.07%), and other not specified (25.17%). Conclusions Given the large population of Africa, the total reported cases may be underestimated when compared with other continents due to the lack of a central brain tumor registry in Africa. A comprehensive knowledge of CNS tumors in Africa is critical to population-based research and improving the current healthcare system.

Background: The types of central nervous system (CNS) tumors in a patient population with a history of military service were compared to the types of CNS tumors in a similar patient population without a military service history to determine if a relationship exists between military service and CNS tumor type. Methods: This study analyzed data for adult patients diagnosed with an intra- or extra-axial CNS tumor from January 2016 to July 2019. One cohort was constructed of patients who had a history of military service (MIL), and the other cohort was made of patients who did not have a history of military service (NMIL). Appropriate parametric and non-parametric analyses were used to compare frequencies of tumor types between cohorts adjusting for potential confounders. Results: We identified 2001 patients (MIL, n = 190; NMIL, n = 1811). In the MIL cohort, most patients were males, younger, and more racially diverse. In the primary analysis, the MIL cohort showed higher diagnoses of metastatic tumors compared with the NMIL cohort (X 2 (1)= 3.71, p =.05). The MIL cohort also showed lower diagnoses of meningioma compared to the NMIL cohort. There was no statically significant difference between cohorts or tumors after adjusting for primary source by gender. Conclusions: MIL experience was associated with lower diagnoses of meningioma but higher diagnoses of metastatic cancer, providing support that there may be potential differences in tumor types between patients with a history of military service and those without military history regarding primary CNS tumor frequency.

Multiple studies have demonstrated a correlation with military service and brain tumors, both for primary tumors and meningiomas. However, there is little comprehensive research on tumor types in the US military population. We evaluated our local brain tumor bank to identify types and correlates of brain tumors in a military vs. civilian population in central Texas. PURPOSE The purpose of our research was to describe brain cancers in the military population when compared to nonmilitary population in our local database. METHODS Retrospective data was derived from our brain tumor bank at the Baylor Scott & White in central Texas. Tumors were classified based on final histologically confirmed diagnosis when possible. Demographics and correlates. We obtained military background by chart review of notes, occupation, insurance provider and relationship to insured in the electronic medical record. RESULTS Data from 53 veterans and 170 non-veterans were analyzed. The most common tumor type in Veterans was glioblastoma multiforme (20.75%) followed by metastatic lesions (18.87%), meningiomas (16.98%) and adenomas (13.21%). There was no statistically significant difference in distribution of tumor types between civilians and controls. Demographic analysis revealed an older age of diagnosis in Veterans than civilians for the top three most common tumor types with glioblastoma multiforme (67.64 vs 61.65) with a difference of 5.99 years; metastatic lesions (69.4 vs 61.22) with a difference of 8.18 years and meningiomas (63.88 vs 57.57) with a difference of 6.31 years. (military versus civilians average age, respectively). CONCLUSION The age of onset for the three most common types of tumors were older in the Veteran population than civilians by an average of 6.82 years. More research into the older age of diagnosis for the Veterans should be further explored. Our research did not find any correlation between military service and tumor types as previous studies have shown.