Adora2A downregulation promotes caffeine neuroprotective effect against LPS-induced neuroinflammation in the hippocampus.

Caffeine has been extensively studied in the context of CNS pathologies as many researchers have shown that consuming it reduces pro-inflammatory biomarkers, potentially delaying the progression of neurodegenerative pathologies. Several lines of evidence suggest that adenosine receptors, especially A1 and A2A receptors, are the main targets of its neuroprotective action. We found that caffeine pretreatment 15 min before LPS administration reduced the expression of Il1b in the hippocampus and striatum. The harmful modulation of caffeine-induced inflammatory response involved the downregulation of the expression of A2A receptors, especially in the hippocampus. Caffeine treatment alone promoted the downregulation of the adenosinergic receptor Adora2A; however, this promotion effect was reversed by LPS. Although administering caffeine increased the expression of the enzymes DNA methyltransferases 1 and 3A and decreased the expression of the demethylase enzyme Tet1, this effect was reversed by LPS in the hippocampus of mice that were administered Caffeine + LPS, relative to the basal condition; no significant differences were observed in the methylation status of the promoter regions of adenosine receptors. Finally, the bioinformatics analysis of the expanded network demonstrated the following results: the Adora2B gene connects the extended networks of the adenosine receptors Adora1 and Adora2A; the Mapk3 and Esr1 genes connect the extended Adora1 network; the Mapk4 and Arrb2 genes connect the extended Adora2A network with the extended network of the proinflammatory cytokine Il1ß. These results indicated that the anti-inflammatory effects of acute caffeine administration in the hippocampus may be mediated by a complex network of interdependencies between the Adora2B and Adora2A genes.

Impact of neuroinflammation on epigenetic transcriptional control of Sonic Hedgehog members in the central nervous system.

Sonic Hedgehog (Shh) signaling plays a critical role during central nervous system (CNS) development, and its dysregulation leads to neurological disorders. Nevertheless, little is known about Shh signaling regulation in the adult brain. Here, we investigated the contribution of DNA methylation on the transcriptional control of Shh signaling pathway members and its basal distribution impact on the brain, as well as its modulation by inflammation. The methylation status of the promoter regions of these members and the transcriptional profile of DNA-modifying enzymes (DNA Methyltransferases - DNMTs and Tet Methylcytosine Dioxygenase - TETs) were investigated in a murine model of neuroinflammation by qPCR. We showed that, in the adult brain, methylation in the CpG promoter regions of the Shh signaling pathway members was critical to determine the endogenous differential transcriptional pattern observed between distinct brain regions. We also found that neuroinflammation differentially modulates gene expression of DNA-modifying enzymes. This study reveals the basal transcriptional profile of DNMTs and TETs enzymes in the CNS and demonstrates the effect of neuroinflammation on the transcriptional control of members of the Shh Signaling pathway in the adult brain.

Preoperative scale proposal based on clinical outcome for elderly patients with ruptured intracranial aneurysms undergoing microsurgery.

INTRODUCTION: Life expectancy in individuals has increased in recent years. There is no consensus in the literature on the best treatment for a ruptured aneurysm in the elderly (> 60 years), but some places only have microsurgery as a therapeutic strategy. This work aims to develop a prognostic scale for ruptured intracranial aneurysms in the elderly. MATERIAL AND METHODS: Two thousand five hundred thirty patients with subarachnoid hemorrhage were retrospectively evaluated in the last ten years, and 550 of them were elderly. We developed a prognostic scale from the analysis of medical records, clinical and tomographic features that had statistical significance. Glasgow Coma Outcome (GOS) was the outcome of interest and p value < 0,05 was considered statistically significant. RESULTS: Five hundred fifty patients were evaluated, and the comorbidities that were independent variables for poor prognosis were smoking and arterial hypertension; clinical variables were Hunt-Hess, modified Rankin and Glasgow Coma Scale; tomographic was Fisher scale. Poor outcome was defined as GOS ≤ 3. Poor surgical outcomes were more remarkable in the high-risk factor categories, being 6.41 times higher among individuals who had 3 to 4 risk factors and 8.80 times higher among individuals with 5 to 6 risk factors. CONCLUSION: In some vascular neurosurgery services worldwide, microsurgery is the only therapeutic option. This scale aimed at the elderly patient individualizes the treatment and can predict the clinical outcome in ruptured intracranial aneurysms.

Abducent nerve palsy after microballoon compression of the trigeminal ganglion: Case report.

BACKGROUND: Trigeminal neuralgia (TN) is the most common type of facial neuralgia with incidence of 26.8/100,000 person year. In general, this scenario is characterized by a lancinating, unilateral, paroxysmal pain in the area of the fifth cranial nerve. Several treatment methods, including the injection of ethyl alcohol or butyl alcohol into the ganglion, the glycerol injection into the trigeminal cistern, peripheral nerve divisions, the radiofrequency thermocoagulation of the preganglionic fibers, and radiosurgery has been used for TN. CASE DESCRIPTION: A case of a 74-year-old woman patient who undergone a treatment of TN through a compression of Meckel cave and developed a transient abducent palsy is presented. Complication regarding to a palsy of abducent nerve is discussed as well as the analysis of presumable evolving physiopathology. A critical review of literature was performed. CONCLUSIONS: Among the procedures, we mean that percutaneous microballoon compression (PMC) is the best choice for elderly frail patients, because it had a very low associated mortality-morbidity rate and does not damage permanent the Gasserian ganglion.

Stentoplastia no tratamento precoce das fraturas de coluna em idoso: relato de caso / Stentoplasty for early treatment for spine fracture in elderly: Case report

O objetivo deste artigo é fazer o relato de caso de um paciente idoso, submetido a tratamento cirúrgico de fratura osteoporóticade coluna lombar com um método pouco difundido no Brasil. Normalmente o tratamento instituído é a vertebroplastia oucifoplastia, mas os autores vêm obtendo melhores resultados com a stentoplastia nesta população, método este que envolve acolocação de um stent no corpo vertebral associado a cimento ósseo. Este procedimento fornece mais segurança e estabilidadeà vértebra quando comparado aos métodos tradicionais...

The main purpose of this article is to describe a new method, that has not been used frequently in Brazil. Mostly the physicianshas used the vertebroplasty or kyphoplasty to treat spine fracture, but the authors have been achieving better results with thestentoplasty in this population. This method evolves a vertebral stent inside the fractured bone. This procedure gives the patientmore safety and stability when comparing it to other kind of treament...

Brainstem cavernomas: a surgical challenge.

OBJECTIVE: The authors show their experience with brainstem cavernomas, comparing their data with the ones of a literature review. METHODS: From 1998 to 2009, 13 patients harboring brainstem cavernomas underwent surgical resection. All plain films, medical records and images were reviewed in order to sample the most important data regarding epidemiology, clinical picture, radiological findings and surgical outcomes, as well as main complications. RESULTS: The mean age was 42.4 years (ranging from 19 to 70). No predominant gender: male-to-female ratio, 6:7. Pontine cases were more frequent. Magnetic resonance imaging was used as the imaging method to diagnose cavernomas in all cases. The mean follow-up was 71.3 months (range of 1 to 138 months). Clinical presentation was a single cranial nerve deficit, VIII paresis, tinnitus and hearing loss (69.2%). All 13 patients underwent resection of the symptomatic brainstem cavernoma. Complete removal was accomplished in 11 patients. Morbidity and mortality were 15.3 and 7.6%, respectively. CONCLUSIONS: Cavernomas can be resected safely with optimal surgical approach (feasible entry zone) and microsurgical techniques, and the goal is to remove all lesions with no cranial nerves impairment.

Brainstem cavernomas: a surgical challenge / Cavernomas de tronco: desafio cirúrgico

Objective: The authors show their experience with brainstem cavernomas, comparing their data with the ones of a literature review. Methods: From 1998 to 2009, 13 patients harboring brainstem cavernomas underwent surgical resection. All plain films, medical records and images were reviewed in order to sample the most important data regarding epidemiology, clinical picture, radiological findings and surgical outcomes, as well as main complications. Results: The mean age was 42.4 years (ranging from 19 to 70). No predominant gender: male-to-female ratio, 6:7. Pontine cases were more frequent. Magnetic resonance imaging was used as the imaging method to diagnose cavernomas in all cases. The mean follow-up was 71.3 months (range of 1 to 138 months). Clinical presentation was a single cranial nerve deficit, VIII paresis, tinnitus and hearing loss (69.2%). All 13 patients underwent resection of the symptomatic brainstem cavernoma. Complete removal was accomplished in 11 patients. Morbidity and mortality were 15.3 and 7.6%, respectively. Conclusions: Cavernomas can be resected safely with optimal surgical approach (feasible entry zone) and microsurgical techniques, and the goal is to remove all lesions with no cranial nerves impairment.

Objetivo: Os autores mostram sua experiência com cavernomas de tronco cerebral, comparando seus dados com os de uma revisão da literatura. Métodos: De 1998 a 2009, 13 pacientes com cavernoma de tronco cerebral foram submetidos a ressecção cirúrgica. Todos os filmes, prontuários e imagens foram revisados para exposição dos dados mais importantes, como epidemiologia, detalhes clínicos, achados radiológicos e resultados cirúrgicos, bem como as principais complicações. Resultados: A média de idade foi de 42,4 anos (variação de 19 a 70). Não houve predominância de gênero na taxa masculino versus feminino, 6:7. Os casos pontinos foram os mais frequentes. Ressonância nuclear magnética foi o método de imagem para o diagnóstico de cavernomas em todos os casos. A média do acompanhamento foi de 71,3 meses (variação de 1 a 138 meses). A apresentação clínica mais frequente foi a paresia do VIII nervo craniano, tinitus e perda auditiva (69,2%). Todos os 13 pacientes com cavernomas de tronco sintomáticos foram submetidos à ressecção cirúrgica. A remoção total foi realizada em 11 pacientes. A morbidade e a mortalidade foram de 15,3 e 7,6%, respectivamente. Conclusão: Os cavernomas podem ser seguramente ressecados por meio de acessos cirúrgicos ideais (zonas de entrada seguras) e técnicas de microcirurgia, sendo que o objetivo é remover toda a lesão sem o comprometimento dos nervos cranianos.

Análise de crescimento de mamona semeada em diferentes épocas / Growth of castor sown at different times

O objetivo deste trabalho foi estudar os efeitos dos fatores externos no crescimento, desenvolvimento e na produtividade da planta de mamona. O experimento foi realizado com a cultivar 'BRS Energia' semeada em três épocas nas safras 2008/09 e 2009/10 em Pelotas - RS. As variáveis avaliadas foram a taxa de crescimento relativo (TCR), taxa assimilatória líquida (TAL), produtividade e as principais variáveis meteorológicas. A maior taxa de crescimento relativo e assimilatória líquida ocorre nos períodos de temperatura média de 22,5 a 25,7°C e insolação média diária maior que seis horas, que coincidem com as semeaduras de novembro e dezembro na região de Pelotas, enquanto as maiores produtividades ocorrem nas semeaduras de outubro e novembro.

The objective was to study external effects on growth, development and plant productivity. The experiment was conducted with 'BRS Energia' sown at three times in 2008/09 and 2009/10 seasons in Pelotas, Southern Brazil. It was evaluated the relative growth rate (RGR), net assimilation rate (NAR), yield and the main meteorological variables. The highest relative growth rate and net assimilation rate occurred at an average temperature of 22.5 to 25.7°C and average daily insolation greater than six hours, which coincide with November and December sowings in Southern Brazil. The highest yields were observed in October and November sowings.

Surgical management of brainstem cavernous malformations.

Bleeding from brainstem cavernomas may cause severe deficits due to the absence of non-eloquent nervous tissue and the presence of several ascending and descending white matter tracts and nerve nuclei. Surgical removal of these lesions presents a challenge to the most surgeons. The authors present their experience with the surgical treatment of 43 patients with brainstem cavernomas. Important aspects of microsurgical anatomy are reviewed. The surgical management, with special focus on new intraoperative technologies as well as controversies on indications and timing of surgery are presented. According to several published studies the outcome of brainstem cavernomas treated conservatively is poor. In our experience, surgical resection remains the treatment of choice if there was previous hemorrhage and the lesion reaches the surface of brainstem. These procedures should be performed by experienced neurosurgeons in referral centers employing all the currently available technology.

Tratamento cirúrgico dos aneurismas intracranianos em idosos / Surgical treatment of intracranial aneurysms in elderly

Há cerca de vinte anos, pacientes idosos com diagnóstico de aneurisma cerebral eram excluídos de quaisquer modalidades de intervenção cirúrgica devido ao prognóstico reservado. Com o rápido envelhecimento da população, houve um aumento consistente na prevalência de hemorragia subaracnóide, associada a todas as suas complicações. A deterioração neurológica tardia, advinda do vasoespasmo cerebral, é uma das principais causas de morbi-mortalidade nesse grupo de pacientes. Dessa forma, a estratégia de tratamento específico para aneurismas cerebrais em idosos tem sido aprimorada.

Is sagittal sinus resection in falcine meningiomas a factor of bad surgical outcome?

OBJECTIVE: Meningiomas arising purely from the falx below the longitudinal sinus represents a surgical challenge for the neurosurgeon. The authors discuss the new aspects of surgical details that may avoid complications and determine the prognosis. MATERIALS AND METHODS: We retrospectively evaluated our surgical experience from June 2004 to January 2010. Seventy patients harboring falcine meningiomas were included and submitted for surgical resection. All historical records, office charts and images were reviewed in order to sample the most important data regarding epidemiology, clinical pictures, radiological findings and surgical results, as well as the main complications. The patients were divided into three main groups: anterior third 32 patients (Group A), middle third 15 patients (Group B), 23 patients in the posterior third of falx (Group C). RESULTS: In Group A, total macroscopic resection was achieved in 31 out of 32 cases (96.87%). Twenty five patients had Rankin 0, five patients had Rankin 1-2, two patients had Rankin 6. In Group B (15 patients), 10 patients had gross resection and Rankin 0, four patients had Rankin 1-2 and one patient had Rankin 6. In Group C (23 patients), 20 patients were absolutely able, Rankin score 0, after six months postoperative period (83.3% had excellent results) and no mortality. Four cases had Rankin score 1 - 2 (16.6%). Ten cases (43.47%) had Simpson I resection and ten cases (43.47%) had Simpson II. CONCLUSION: Despite larger lesion volumes, Group A meningiomas had a better outcome due to the position they were in, the tumor and surrounding structures. The preoperative preparation and surgical planning can preserve sagittal sinus; but in some cases, this is not possible. Sagittal sinus resection, as proven by this paper, is still a factor of bad surgical outcome. In the middle and posterior third, resection of sagittal sinus is a factor of a bad outcome, due to cerebral infartion.

O papel da abordagem endoscópica trans-esfenoidal extendita no manejo dos meningiomas do tubéculo da sela: existe alguma indicação? / The role of the extended transsphenoidal endoscopic approach in tuberculum sellae meningeomas management. Is there any indication

A abordagem endonasal endoscópica é um novo armamentarium cirúrgico no tratamento das patologias da base do crânio. A abordagem endoscópica trans-esfenoidal extendida para a fossa anterior da base do crânio é uma de suas variações. Meningeomas do tubérculo da sela são lesões únicas que correspondem a 5 a 10% de todos os meningeomas intracranianos. Eles caracterizam-se por deterioração visual precoce. O melhor manejo destes tumores é a ressecção cirúrgica radical, que é realizada historicamente mediante craniotomia. Para pequenos meningeomas do tubérculo selar situados na linha média a abordagem a abordagem endoscópica trans-esfenoidal extendida pode ser indicada. Durante período de 30 meses, 10 meningeomas do tubérculo da sela foram operados por craniotomia fronto-orbital (7 casos) ou pterional (2 casos)unilateral e um paciente por abordagem trans-esfenoidal endoscópica. Nós apresentamos este último caso e discutimos as nuances técnicas bem como os fatores envolvidos na seleção da melhor abordagem.

Labeling index in pituitary adenomas evaluated by means of MIB-1: is there a prognostic role? A critical review.

OBJECTIVE: The present article presents an overview of the literature, and analyses the methods and the primary questions related to assessment of proliferation index using the Ki-67/MIB-1 labeling index in pituitary adenomas. Although atypical adenomas are characterized by their atypical morphological features by an elevated mitotic index, a Ki-67 (MIB-1) labeling index greater than 3% and extensive nuclear staining for p53, use of the proliferation index (LI) of pituitary adenomas in assessing the degree of tumor aggressiveness is a controversial topic in the literature, and there are disparate results involving many studies. METHODS: A review of literature was carried out to correlate the role of Ki-67 LI and its correlation with clinical findings, tumor size, invasiveness, recurrence, adenoma subtype, adenoma doubling time, and pituitary carcinomas is addressed. RESULTS: The prognosis cannot be predicted on the basis of the Ki-67 LI alone. Although there is no direct relation between Ki-67 LI and some of these variables and controversial data were found regarding some topics, our review justify the use of Ki-67 in the analysis of pituitary adenomas as an additional information for clinical decision. CONCLUSION: Although assessment of proliferative may be helpful in predicting subsequent tumor recurrence or invasiveness, there are many other important and as yet unidentified factors pituitary tumors. It is clear that further research is needed to clarify these molecular mechanisms to predict those with a potentially poor clinical outcome.

Craniofaringiomas: análise crítica da literatura: [revisão] / Management of craniopharyngiomas: [review]

Os autores fazem uma revisão estruturada da literatura sobre o manejo dos craniofaringiomas e sobre as principais complicações do tratamento cirúrgico. As diferentes vias de acesso são discutidas, bem como o prognóstico.

Benefício terapêutico do magnésio na fisiopatologia do vasoespasmo após hemorragia subaracnóide: [revisão] / Magnesium in subarachnoide hemorrhage: useful with benefits?: [review]

O vasoespasmo tem sido causador de grande numero de sequelas e óbitos após o evento da hemorragia subaracnóide.Várias hipóteses fisiopatológicas para seu desenvolvimento vêm sendo estudadas na literatura, todavia o envolvimento do magnésio na gênese e como substância terapêutica vem ganhando destaque cada vez maior. Os autores procuram identificar os pontos de relevância da cadeia de equilíbrio entre o cálcio e magnésio nas bombas de membrana endoteliais e o beneficio do mesmo na terapêutica, baseando-se na literatura revisada. A infusão de sulfato de magnésio endovenosa no período em que o vasoespasmo se instala parece ser um conduta extremamente útil e necessária no relaxamento da musculatura endotelial e faz parte hoje da maior parte dos protocolos de tratamento do vasoespasmo pós hemorragia subaracnóide.