Neuronal death after perinatal cerebral hypoxia-ischemia: Focus on autophagy-mediated cell death.

Neonatal hypoxic-ischemic encephalopathy is a critical cerebral event occurring around birth with high mortality and neurological morbidity associated with long-term invalidating sequelae. In view of the great clinical importance of this condition and the lack of very efficacious neuroprotective strategies, it is urgent to better understand the different cell death mechanisms involved with the ultimate aim of developing new therapeutic approaches. The morphological features of three different cell death types can be observed in models of perinatal cerebral hypoxia-ischemia: necrotic, apoptotic and autophagic cell death. They may be combined in the same dying neuron. In the present review, we discuss the different cell death mechanisms involved in neonatal cerebral hypoxia-ischemia with a special focus on how autophagy may be involved in neuronal death, based: (1) on experimental models of perinatal hypoxia-ischemia and stroke, and (2) on the brains of human neonates who suffered from neonatal hypoxia-ischemia.

Gliossarcoma de tronco cerebral em paciente pediátrico: relato de caso

Os autores relatam o caso de um paciente branco, de quatro anos de idade, com comprometimento neurológico progressivo. Tomografia computadorizada do crânio e ressonância magnética evidenciaram lesão expansiva no tronco cerebral. Subseqüentemente, foi feito diagnóstico histopatológico de gliossarcoma. Trata-se de um tumor raro do sistema nervoso central que, na grande maioria dos casos, acomete pacientes acima dos 40 anos de idade e tem localização supratentorial. Há poucos casos relatados de gliossarcomas em crianças, sobretudo na região infratentorial. Dados epidemiológicos, assim como achados mais freqüentes na tomografia computadorizada e ressonância magnética, são discutidos.

Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [<1.0 mmol/L] for at least 2 h) were identified among 26 patients. During GD, we found a significant increase of CMD lactate (from 4±2.3 to 5.4±2.9 mmol/L), pyruvate (126.9±65.1 to 172.3±74.1 μmol/L), and lactate/pyruvate ratio (LPR; 27±6 to 35±9; all, p<0.005), while brain oxygen and blood lactate remained normal. Dynamics of lactate and glucose supply during GD were further studied by analyzing the relationships between blood and CMD samples. There was a strong correlation between blood and brain lactate when LPR was normal (r=0.56; p<0.0001), while an inverse correlation (r=-0.11; p=0.04) was observed at elevated LPR >25. The correlation between blood and brain glucose also decreased from r=0.62 to r=0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.

Hematoma intraparenquimatoso cerebral espontâneo: aspectos à tomografia computadorizada

OBJETIVO: Identificar os aspectos mais freqüentes do hematoma intraparenquimatoso cerebral espontâneo observados na tomografia computadorizada. MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, os exames de tomografia computadorizada de 250 pacientes com hematoma intraparenquimatoso cerebral espontâneo, provenientes de três diferentes hospitais da cidade do Rio de Janeiro. RESULTADOS: O hematoma intraparenquimatoso cerebral profundo foi o de maior incidência, equivalendo a 54,4% (136 casos), seguido do lobar com 34,8% (87 casos). Mais raramente, observou-se sangramento cerebelar em 8,4% (21 casos) e do tronco cerebral em 2,4% (seis casos) dos pacientes. CONCLUSÃO: A cefaléia foi o sintoma mais comum e a hipertensão arterial foi o sinal mais freqüentemente apresentado. A drenagem do hematoma para o sistema ventricular ocorreu mais comumente nos hematoma profundos.

Multiphase Postmortem Computed Tomography Angiography in Pediatrics: A Case Report.

Postmortem imaging techniques, especially postmortem computed tomography, have become integral tools in forensic investigations. Multiphase postmortem computed tomography angiography (MPMCTA) visualizes the vascular system in detail and makes it possible to evaluate the perfusion of even the smallest vessels. Although the technique has been well described for adults, no pediatric cases have been reported and no pediatric protocol has been established for this type of investigation. We present the case a 7-year-old child for which we used a previously described MPMCTA protocol and adapted values of perfusion, with the same technical equipment as for adult cases. Our main objective was to propose a perfusion protocol adapted for the investigation of infants and children. Moreover, we discuss both the difficulties that we encountered and possible ways to further improve the investigation of pediatric cases by MPMCTA.

Alterações ultra-sonográficas na gravidez Rh negativo sensibilizada avaliada pela espectrofotometria do líquido amniótico e pela dopplervelocimetria da artéria cerebral média

OBJETIVO: Avaliar e confrontar a presença de alterações ultra-sonográficas nas gestações Rh negativo sensibilizadas, quando a anemia fetal foi determinada ou pela espectrofotometria do líquido amniótico, ou pela dopplervelocimetria da artéria cerebral média. MATERIAIS E MÉTODOS: Observacional descritivo com grupo de comparação. Nosso grupo de estudo foi constituído por 99 pacientes, avaliadas no período de janeiro de 1995 a janeiro de 2004. Foram analisados e comparados dois grupos: 74 gestantes sensibilizadas pelo fator Rh cuja anemia fetal foi acompanhada pela espectrofotometria (grupo SE) e 25 gestantes sensibilizadas pelo fator Rh cuja anemia fetal foi acompanhada pela dopplervelocimetria (grupo SD). Avaliamos a presença ou não de alterações ultra-sonográficas no acompanhamento pré-natal e confrontamos os dois grupos de estudo. RESULTADOS: No grupo cuja anemia fetal foi acompanhada através da espectrofotometria (grupo SE), apuramos modificações placentárias, principalmente o aumento da espessura e sua alteração textural, mais assiduamente que as encontradiças no grupo de gestantes sensibilizadas, em que a anemia foi determinada através da dopplervelocimetria (grupo SD) (64% X 32%, p = 6,294). CONCLUSÃO: As alterações ultra-sonográficas foram detectadas em dobro quando a anemia foi avaliada pela espectrofotometria em comparação com o grupo seguido pela dopplervelocimetria.

Erratum of initial paper: Postmortem computed tomography angiography vs. conventional autopsy: advantages and inconveniences of each method.

PURPOSE: Postmortem computed tomography angiography (PMCTA) was introduced into forensic investigations a few years ago. It provides reliable images that can be consulted at any time. Conventional autopsy remains the reference standard for defining the cause of death, but provides only limited possibility of a second examination. This study compares these two procedures and discusses findings that can be detected exclusively using each method. MATERIALS AND METHODS: This retrospective study compared radiological reports from PMCTA to reports from conventional autopsy for 50 forensic autopsy cases. Reported findings from autopsy and PMCTA were extracted and compared to each other. PMCTA was performed using a modified heart-lung machine and the oily contrast agent Angiofil® (Fumedica AG, Muri, Switzerland). RESULTS: PMCTA and conventional autopsy would have drawn similar conclusions regarding causes of death. Nearly 60 % of all findings were visualized with both techniques. PMCTA demonstrates a higher sensitivity for identifying skeletal and vascular lesions. However, vascular occlusions due to postmortem blood clots could be falsely assumed to be vascular lesions. In contrast, conventional autopsy does not detect all bone fractures or the exact source of bleeding. Conventional autopsy provides important information about organ morphology and remains the only way to diagnose a vital vascular occlusion with certitude. CONCLUSION: Overall, PMCTA and conventional autopsy provide comparable findings. However, each technique presents advantages and disadvantages for detecting specific findings. To correctly interpret findings and clearly define the indications for PMCTA, these differences must be understood.

Alterações parenquimatosas na trombose venosa cerebral: aspectos da ressonância magnética e da angiorressonância

OBJETIVO: Determinar a freqüência e localização das alterações parenquimatosas da trombose venosa cerebral nos exames de ressonância magnética e de angiorressonância, bem como a correlação com o território e a drenagem venosa comprometida. MATERIAIS E MÉTODOS: Foram analisados exames de 21 pacientes realizados entre 1996 e 2004, com diagnóstico clínico e radiológico de trombose venosa cerebral em exames de ressonância magnética e de angiorressonância nas seqüências 2D PC, 3D PC e 3D TOF com contraste paramagnético. Análise estatística foi realizada com o teste do qui quadrado. Quatro pacientes tinham exames de controle e três realizaram angiografia por subtração digital. RESULTADOS: Dos 21 pacientes, 18 eram mulheres, todos com idade entre três e 82 anos (média de 40 anos e mediana de 36 anos). Os principais fatores etiológicos foram infecção, uso de contraceptivos orais, reposição hormonal e colagenoses. Predominaram os sintomas de déficit focal, cefaléia, alteração do nível de consciência e convulsões. Por freqüência, as manifestações parenquimatosas foram: edema/infarto de distribuição cortical e/ou subcortical, congestão venosa e circulação colateral, realce meníngeo e infarto ou edema dos tálamos e núcleos da base. Os principais seios comprometidos foram o sagital superior, o transverso esquerdo, o sigmóide esquerdo e o seio reto, sendo incomum o acometimento dos seios cavernosos e de veias corticais. CONCLUSÃO: A trombose venosa cerebral é causa incomum de acidente vascular encefálico, com prognóstico favorável pelo caráter reversível das lesões. Seu diagnóstico depende fundamentalmente da capacidade do radiologista reconhecer suas formas de apresentação, principalmente nos casos em que ele é sugerido pelas alterações parenquimatosas e não necessariamente pela visualização do trombo. A precisão e a rapidez no diagnóstico permitem o pronto tratamento, reduzindo a morbi-mortalidade da doença.

Cisticercose intradural-extramedular cerebral e espinhal: relato de caso e revisão da literatura

Relato de um caso raro de apresentação de infestação por cisticercose do espaço subaracnóide cerebral e intra-raquiano nas regiões cervical e torácica em mulher de 59 anos de idade, com náuseas, sinais de ataxia cerebelar e perda gradual da sensibilidade nas pernas. O diagnóstico foi feito por meio de imagens por ressonância magnética do cérebro e da coluna cérvico-torácica, que evidenciaram a presença de cistos nos espaços subaracnóides. O exame do líquido cefalorraquiano revelou teste imunológico ELISA positivo e elevado nível de proteína (420 mg/dl), indicativo de atividade da doença. Os parasitos foram removidos cirurgicamente pela necessidade de descompressão da medula espinhal torácica. Breve comentário sobre a patogênese da forma cística da cisticercose espinhal intradural-extramedular, aspectos das imagens de ressonância magnética e tratamento foram feitos com base nos achados de revisão da literatura.

Extended Endoscopic Endonasal Approaches for Cerebral Aneurysms: Anatomical, Virtual Reality and Morphometric Study

Introduction. The purpose of the present contribution is to perform a detailed anatomic and virtual reality three-dimensional stereoscopic study in order to test the effectiveness of the extended endoscopic endonasal approaches for selected anterior and posterior circulation aneurysms. Methods. The study was divided in two main steps: (1) simulation step, using a dedicated Virtual Reality System (Dextroscope, Volume Interactions); (2) dissection step, in which the feasibility to reach specific vascular territory via the nose was verified in the anatomical laboratory. Results. Good visualization and proximal and distal vascular control of the main midline anterior and posterior circulation territory were achieved during the simulation step as well as in the dissection step (anterior communicating complex, internal carotid, ophthalmic, superior hypophyseal, posterior cerebral and posterior communicating, basilar, superior cerebellar, anterior inferior cerebellar, vertebral, and posterior inferior cerebellar arteries). Conclusion. The present contribution is intended as strictly anatomic study in which we highlighted some specific anterior and posterior circulation aneurysms that can be reached via the nose. For clinical applications of these approaches, some relevant complications, mainly related to the endonasal route, such as proximal and distal vascular control, major arterial bleeding, postoperative cerebrospinal fluid leak, and olfactory disturbances must be considered

Involvement of a transforming-growth-factor-beta-like molecule in tumor-cell-derived inhibition of nitric-oxide synthesis in cerebral endothelial cells.

Nitric oxide (NO) has been shown to exert cytotoxic effects on tumor cells. We have reported that EC219 cells, a rat-brain-microvessel-derived endothelial cell line, produced NO through cytokine-inducible NO synthase (iNOS), the induction of which was significantly decreased by (a) soluble factor(s) secreted by DHD/PROb, an invasive sub-clone of a rat colon-carcinoma cell line. In this study, the DHD/PROb cell-derived NO-inhibitory factor was characterized. Northern-blot analysis demonstrated that the induction of iNOS mRNA in cytokine-activated EC219 cells was decreased by PROb-cell-conditioned medium. When DHD/PROb cell supernatant was fractionated by affinity chromatography using Con A-Sepharose or heparin-Sepharose, the NO-inhibitory activity was found only in Con A-unbound or heparin-unbound fractions, respectively, indicating that the PROb-derived inhibitory factor was likely to be a non-glycosylated and non-heparin-binding molecule. Pre-incubation of DHD/PROb-cell supernatant with anti-TGF-beta neutralizing antibody completely blocked the DHD/PROb-derived inhibition of NO production by EC219 cells. Addition of exogenous TGF-beta 1 dose-dependently inhibited NO release by EC219 cells. The presence of active TGF-beta in the DHD/PROb cell supernatant was demonstrated using a growth-inhibition assay. Moreover, heat treatment of medium conditioned by the less invasive DHD/REGb cells, which constitutively secreted very low levels of active TGF-beta, increased both TGF-beta activity and the ability to inhibit NO production in EC219 cells. Thus, DHD/PROb colon-carcinoma cells inhibited NO production in EC219 cells by secreting a factor identical or very similar to TGF-beta.