Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury

Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-kappaB (NF-kappaB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-kappaB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

Os possíveis papéis da S100B na esquizofrenia / Potential roles of S100B in schizophrenia

Evidências científicas do aumento da concentração da proteína S100B no sangue de pacientes esquizofrênicos são muito consistentes. No passado essa informação era principalmente considerada como reflexo da disfunção astroglial ou da barreira hematoencefálica. MÉTODOS: Pesquisa de publicações no PubMed até o dia 15 de junho de 2011 visando estabelecer potenciais ligações entre a proteína S100B e as hipóteses correntes da esquizofrenia. RESULTADOS: A S100B está potencialmente associada com as hipóteses dopaminérgica e glutamatérgica. O aumento da expressão de S100B tem sido detectado em astrócitos corticais em casos de esquizofrenia paranoide, enquanto se observa uma redução da expressão em oligodendrócitos na esquizofrenia residual, dando suporte à hipótese glial. Recentemente, a hipótese da neuroinflamação da esquizofrenia tem recebido atenção crescente. Nesse sentido, a S100B pode funcionar como uma citocina secretada por células gliais, linfócitos CD8+ e células NK, levando à ativação de monócitos e microglia. Além disso, a S100B apresenta propriedades do tipo adipocina e pode estar desregulada na esquizofrenia, devido a distúrbios da sinalização de insulina, levando ao aumento da liberação de S100B e ácidos graxos do tecido adiposo. CONCLUSÃO: A expressão de S100B em diferentes tipos celulares está envolvida em muitos processos regulatórios. Atualmente, não pode ser respondido qual mecanismo relacionado à esquizofrenia é o mais importante

Scientific evidence for increased S100B concentrations in the peripheral blood of acutely ill schizophrenia patients is consistent. In the past, this finding was mainly considered to reflect astroglial or blood-brain barrier dysfunction. METHODS: Using Entrez, PubMed was searched for articles published on or before June 15, 2011, including electronic early release publications, in order to determine other potential links between S100B and current hypotheses for schizophrenia. RESULTS: S100B is potentially associated with the dopamine and glutamate hypotheses. Supporting the glial hypothesis, an increased expression of S100B has been detected in cortical astrocytes of paranoid schizophrenia cases, while decreased oligodendrocytic expression has been observed in residual schizophrenia. Recently, the neuroinflammation hypothesis of schizophrenia has gained attention. S100B may act as a cytokine after secretion from glial cells, CD8+ lymphocytes and NK cells, activating monocytes and microglial cells. Moreover, S100B exhibits adipokine-like properties and may be dysregulated in schizophrenia due to disturbances in insulin signaling, leading to the increased release of S100B and free fatty acids from adipose tissue. DISCUSSION: Dysregulation of pathways related to S100B appears to play a role in schizophrenia. However, S100B is expressed in different cell types and is involved in many regulatory processes. Currently, "the most important" mechanism related to schizophrenia cannot be determined

Alteraciones neuro-funcionales y neuro-endocrinas en una cohorte de pacientes que cursan con trastorno por estrés post traumático / Neuroendocrine and neurofunctional alterations in patient with post traumatic stress disorder

El trastorno por estrés post traumático (TEPT) se perfila en la actualidad como una patología emergente debido a las condiciones de vida modernas cada vez más exigentes y al énfasis epidemiológico y en salud mental por pesquisar las consecuencias de traumas cotidianos, como de aquellos derivados de conflictos bélicos o de la acción de fuerzas de seguridad y orden ciudadanos. Se describe que aproximadamente un 8 por ciento de quienes sufren un trauma experimentarán un cuadro clínico compatible con TEPT. Sin embargo, la larga duración y frecuente cronicidad de estos casos demanda un enorme esfuerzo al equipo de salud y costos elevados a los organismos que acogen a estos pacientes. El presente trabajo tiene por objetivo realizar un estudio neuro-funcional, clínico y de laboratorio en una muestra de 7 pacientes que cursan con un cuadro compatible con TEPT. Método: Se evaluó clínicamente a 7 pacientes que cursaban con TEPT, aplicándoseles una escala de evaluación para esta patología (Escala de Davidson) y el inventario de depresión de Beck. Se obtuvieron muestras de sangre con el objeto de evaluar los niveles de cortisol plasmático y hormonas tiroideas T3, T4 y TSH. Finalmente, los sujetos fueron evaluados a partir de la técnica de neuro SPECT delineándose una serie de Regiones e Interés (ROI) involucradas en la neurobiología del TEPT. Resultados: Se reportan para todos los pacientes de la cohorte estudiada valores elevados en escala Davidson para TEPT y en la escala de Beck para depresión (91.85 y 25.28 respectivamente). Se describen valores promedios normales de cortisol plasmático y de hormonas tiroideas T3, T4 y TSH (17.35 ug/dl, 1.34 ng/ml, 6,98 ug/dl y 2,95 uUI/ml respectivamente). Destaca la presencia de hiper-cortisolemia en tres de los pacientes estudiados. Los hallazgos neuro-funcionales se caracterizan por una hiper-perfusión a nivel de córtex fronto-parietal e hipo-perfusión...

Post Traumatic Stress Disorder (PTSD) is one of the most important emergent pathologies in mental health and is usually associated with current post modern´s life styles and with specific traumatic event such as belic conflicts or incident involving criminal behaviors affecting civilians. It is well known that 8% of victims of a traumatic event will develop PTSD. Furthermore, the chronicity and social impairment associated to this clinical entity requires an enormous effort from mental health’s professionals and huge costs to the systems involved in the rehabilitation of these patients. The aim of this study is to evaluate a sample of 7 patients affected from PTSD in order to understand their clinical characteristics, neuro-functional features and possible neuro-endocrine abnormatilies. Method: 7 patient affected with PTSD were clinically evaluated and submitted to a specific-validated post traumatic scale (Davidson scale) and also to a depression inventory (Beck depression inventory). Then, blood samples were taken in order to assess Neuro- endocrine levels of cortisol in plasma and T3, T4 and TSH levels. Finally, the subjects were studied by means of SPECT, delineating specific Region of Interest (ROI) involved in the neurobiological basis of PTSD. Results: we report on, for the entire sample, high scores on both scales used (Davidson scale: 91.85; Beck inventory: 25.28). These results confirm the previously reported high comorbidity between this two clinical entities. We describe average normal values for plasmatic cortisol levels and thyroid hormones levels T3, T4, TSH (17.35 ug/dl, 1.34 ng/ml, 6.98 ug/dl and 2.95 uUI/ml respectively). It is important to remark the presence of hypercortisolemia in 3 of the patients studied. Neuro-functional features were characterized by a cortical fronto-parietal hyper-perfusion and hypo-perfusion on limbic areas. This results were consistently replicated in the entire sample...

Adjuvant therapy in cerebral malaria.

Cerebral malaria is the most common cause of non-traumatic encephalopathy in the world. The mainstay of therapy is either quinine or artemisinin, both of which are effective antimalarials. The clinical picture of cerebral malaria may persist or even become worse in spite of the clearance of parasites from blood. The death rate is unacceptably high even with effective antimalarials in tertiary care hospitals. The mortality increases in presence of multi organ failure (renal failure, jaundice, respiratory distress, severe anaemia, lactic acidosis, etc.). The pathogenesis of cerebral malaria is multifactorial and includes clogging, sequestration, rosette formation, release of cytokines, cerebral oedema, increased intracranial hypertension, etc. Attempts are made to use adjuvant therapy which will act through alternate mechanisms and address one or more of the pathogenetic processes. In this review, we have discussed the role of corticosteroids, pentoxifylline, desferrioxamine, mannitol and newer agents in the treatment of cerebral malaria. Though the literature on adjuvant therapy in cerebral malaria is large enough, there are a number of shortcomings in the clinical trials, many being open and non randomized or of very small sample size. Further research is of utmost importance through large multicentric, double-blind controlled trials to show the efficacy of any of these drugs.