Expression of miRNAs and Their Cooperative Regulation of the Pathophysiology in Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of injury-related death and disability worldwide. Effective treatment for TBI is limited and many TBI patients suffer from neuropsychiatric sequelae. The molecular and cellular mechanisms underlying the neuronal damage and impairment of mental abilities following TBI are largely unknown. Here we used the next generation sequencing platform to delineate miRNA transcriptome changes in the hippocampus at 24 hours and 7 days following TBI in the rat controlled cortical impact injury (CCI) model, and developed a bioinformatic analysis to identify cellular activities that are regulated by miRNAs differentially expressed in the CCI brains. The results of our study indicate that distinct sets of miRNAs are regulated at different post-traumatic times, and suggest that multiple miRNA species cooperatively regulate cellular pathways for the pathological changes and management of brain injury. The distinctive miRNAs expression profiles at different post-CCI times may be used as molecular signatures to assess TBI progression. In addition to known pathophysiological changes, our study identifies many other cellular pathways that are subjected to modification by differentially expressed miRNAs in TBI brains. These pathways can potentially be targeted for development of novel TBI treatment

Human Flt3L Generates Dendritic Cells from Canine Peripheral Blood Precursors: Implications for a Dog Glioma Clinical Trial

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and carries a dismal prognosis. We have developed a conditional cytotoxic/immunotherapeutic approach using adenoviral vectors (Ads) encoding the immunostimulatory cytokine, human soluble fms-like tyrosine kinase 3 ligand (hsFlt3L) and the conditional cytotoxic molecule, i.e., Herpes Simplex Type 1- thymide kinase (TK). This therapy triggers an anti-tumor immune response that leads to tumor regression and anti-tumor immunological memory in intracranial rodent cancer models. We aim to test the efficacy of this immunotherapy in dogs bearing spontaneous GBM. In view of the controversy regarding the effect of human cytokines on dog immune cells, and considering that the efficacy of this treatment depends on hsFlt3L-stimulated dendritic cells (DCs), in the present work we tested the ability of Ad-encoded hsFlt3L to generate DCs from dog peripheral blood and compared its effects with canine IL-4 and GM-CSF.Our results demonstrate that hsFlT3L expressed form an Ad vector, generated DCs from peripheral blood cultures with very similar morphological and phenotypic characteristics to canine IL-4 and GM-CSF-cultured DCs. These include phagocytic activity and expression of CD11c, MHCII, CD80 and CD14. Maturation of DCs cultured under both conditions resulted in increased secretion of IL-6, TNF-alpha and IFN-gamma. Importantly, hsFlt3L-derived antigen presenting cells showed allostimulatory potential highlighting their ability to present antigen to T cells and elicit their proliferation.These results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine GBM. Our data further support the translation of hsFlt3L to be used for dendritic cells' vaccination and gene therapeutic approaches from rodent models to canine patients and its future implementation in human clinical trials

Benign external hydrocephalus: a review, with emphasis on management

Benign external hydrocephalus in infants, characterized by macrocephaly and typical neuroimaging findings, is considered as a self-limiting condition and is therefore rarely treated. This review concerns all aspects of this condition: etiology, neuroimaging, symptoms and clinical findings, treatment, and outcome, with emphasis on management. The review is based on a systematic search in the Pubmed and Web of Science databases. The search covered various forms of hydrocephalus, extracerebral fluid, and macrocephaly. Studies reporting small children with idiopathic external hydrocephalus were included, mostly focusing on the studies reporting a long-term outcome. A total of 147 studies are included, the majority however with a limited methodological quality. Several theories regarding pathophysiology and various symptoms, signs, and clinical findings underscore the heterogeneity of the condition. Neuroimaging is important in the differentiation between external hydrocephalus and similar conditions. A transient delay of psychomotor development is commonly seen during childhood. A long-term outcome is scarcely reported, and the results are varying. Although most children with external hydrocephalus seem to do well both initially and in the long term, a substantial number of patients show temporary or permanent psychomotor delay. To verify that this truly is a benign condition, we suggest that future research on external hydrocephalus should focus on the long-term effects of surgical treatment as opposed to conservative management

Observações sobre o deslocamento da dura-máter nas punções cisternais laterais

Estudo da anatomia dinâmica da punção cisternal lateral (suboccipital e C1-2) em cadáveres frescos, sob visão direta da dura-máter da junção crânio-vertebral. O deslocamento («tenda») da dura foi observado em todas as punções (n = 42), em média 3,46 mm (2 a 6 mm)