Environmental enrichment reduces brain excitability in adult rats overnourished during lactation / Enriquecimento ambiental reduz excitabilidade cerebral em ratos adultos hipernutridos durante a lactação

ABSTRACT Objective: This study aimed to analyze whether exposure to environmental enrichment (EE) during the juvenile phase of life interferes with the electrical activity of the adult rat brain. In addition, the present research also investigated whether this putative effect on brain electrical activity could be affected by prior overnutrition during lactation. Electrophysiology was measured through cortical spreading depression (CSD), a phenomenon related to brain excitability. Methods: Wistar rats were suckled in litters of either nine or three pups, forming the nourished (N) or overnourished (ON) groups, respectively. At 36 days old, half of the animals from each nutritional condition were exposed to EE. The other half was kept in the standard environment (SE). At 90-120 days of life, each animal was anesthetized for CSD recordings. Results: Overnutrition during lactation caused increases (p < 0.05) in body and brain weights. The EE decelerated CSD propagation velocity regardless of nutritional state during lactation (p < 0.001). The CSD deceleration in the N-EE group was 23.8% and in the ON-EE group was 15% in comparison with the N-SE and ON-SE groups, respectively. Conclusion: Our data demonstrated that EE exposure in the juvenile phase of the rat's life reduced brain excitability, and this effect was observed even if animals were overnourished during lactation. An EE could be considered an adjuvant therapeutic resource to modulate brain excitability.

RESUMO Objetivo: Este estudo analisou se a exposição ao ambiente enriquecido durante a fase juvenil da vida interferiria na atividade elétrica do cérebro de ratos adultos. Além disso, a presente pesquisa também investigou se esse provável efeito na atividade elétrica cerebral poderia ser afetado pela hipernutrição durante a lactação. A eletrofisiologia foi medida através da depressão alastrante cortical, um fenômeno relacionado à excitabilidade cerebral. Métodos: Ratos Wistar foram amamentados em ninhadas de nove ou três filhotes, formando os grupos nutridos ou hipernutridos, respectivamente. Aos 36 dias, metade dos animais de cada condição nutricional foram expostos ao ambiente enriquecido. A outra metade foi mantida na condição de ambiente padrão. Aos 90-120 dias de vida, foram obtidos os registros da depressão alastrante cortical. Resultados: A hipernutrição durante a lactação causou incrementos (p < 0,05) nos pesos corporal e cerebral.O Ambiente Enriquecido desacelerou a velocidade de propagação da depressão alastrante cortical independentemente do estado nutricional durante a lactação (p < 0,001). A desaceleração da depressão alastrante cortical no grupo nutrido/ambiente enriquecido foi de 23,8% e no grupo hipernutrido/ambiente enriquecido foi de 15% em comparação com os grupos nutrido/ambiente padrão e hipernutrido/ambiente padrão, respectivamente. Conclusão: Nossos dados demonstram que a exposição ao ambiente enriquecido na fase juvenil da vida do rato reduz a excitabilidade cerebral, e esse efeito pode ser observado mesmo se os animais estiverem hipernutridos durante a lactação. O ambiente enriquecido pode ser considerado um recurso terapêutico adjuvante para modular a excitabilidade cerebral.

History of Migraine and Volume of Brain Infarcts: The Italian Project on Stroke at Young Age (IPSYS) / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated. METHODS: In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status. RESULTS: A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm³ [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm³ [IQR, 0.8 to 10.1], P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm³ [IQR, 3.4 to 16.6]). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio [MR], 1.64; 95% confidence interval [CI], 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54). CONCLUSIONS: These findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine.

Antioxidant extract counteracts the effects of aging on cortical spreading depression and oxidative stress in the brain cortex

Abstract Purpose: To investigate the effects of Murici extract on the brain excitability-dependent phenomenon known as cortical spreading depression (CSD) and on brain oxidative stress. Methods: Adult and aged Wistar rats were supplemented with murici extract (150 mg/kg/day or 300 mg/kg/day) by gavage for fifteen days. Afterwards, the animals were submitted to a CSD electrophysiological recording and to brain oxidative stress evaluation. Results: Our results showed that aging decreased CSD propagation velocity, catalase activity and glutathione/oxidized glutathione ratio (GSH/GSSG) in the brain cortex of the rats, and increased malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activity. The highest dose (300 mg/kg/day) of murici extract accelerated CSD, whereas the lowest (150mg/kg/day) decelerated, in both adult and aged animals. In contrast, aged animals supplemented with murici extract in both doses presented low MDA levels and high GSG/GSSG ratio in comparison to the control-aged animals. Conclusion: Murici extract supplementation seems to revert detrimental effects in aged brains and could be considered as a strategy in the treatment of pathologies related to aging and cortical spreading depression.

Postoperative Transient Neurologic Dysfunction: A Proposal for Pathophysiology

BACKGROUND AND PURPOSE: Sudden neurological deterioration which cannot be explained by structural change, ischemia or seizure is often observed among neurosurgical patients. We aimed to provide new insight into the pathophysiology of postoperative transient neurologic dysfunction. METHODS: We describe prolonged but fully reversible focal neurologic dysfunction of unknown origin based on the initial evaluation in 8 patients who had received encephalo-duro-arterio-synangiosis for moyamoya disease. We performed brain imaging, including diffusion weighted imaging and perfusion magnetic resonance imaging or single photon emission computed tomography, and electroencephalography (EEG) during the episodes and after resolution of the symptoms. RESULTS: The symptoms consisted of dysarthria, hemiparesis, or hemiparesthesia of limbs contralateral to the operated side. These symptoms developed between 12 hours and 8 days after surgery and lasted between 12 hours and 17 days. Structural imaging did not show any significant interval change compared with the immediate postoperative images. Perfusion imaging showed increased cerebral blood flow in the symptomatic hemisphere. EEG revealed low amplitude arrhythmic slowing in the corresponding hemisphere. Follow-up imaging and EEG after recovery did not show any abnormalities. CONCLUSIONS: Transient neurologic dysfunction can occur during the postoperative period of brain surgery. Although this may last more than usual transient ischemic attack or seizure, it eventually resolves regardless of treatment. Based on our observation, we propose that this is the manifestation of the transient cortical depression triggered by mechanical stimulation, analogous to migraine aura associated with cortical spreading depression.

Análise da relação entre o estilo de vida da população economicamente ativa e a prevalência da depressão / Analysis of the relationship between the lifestyle of the economically active population and the prevalence of depression

A depressão é caracterizada como um distúrbio multifatorial da área afetiva ou do humor, exerce impacto funcional e envolve inúmeros aspectos da de ordem biológica, psicológica e social. A depressão representa, atualmente, um importante problema de saúde pública. A pesquisa foi desenvolvida com o objetivo de analisar a relação entre o estilo de vida da população economicamente ativa e a prevalência da depressão. Tratase de uma análise empírica desenvolvida com dados secundários, sob enfoque quantitativo, tendo como unidade de análise a Região Nordeste. Realizou-se estatística descritiva Regressão de Poisson nas análises bi e multivariada para testar a associação entre a variável resposta e explicativas. A prevalência da depressão para população da Região Nordeste, na faixa etária de 18 anos ou mais, foi de 5,6%. As variáveis que, no modelo multivariado final, apresentaram-se como fatores associados ao risco de depressão, foram mulheres, a faixa etária de 40-59 anos, separadas (os) ou divorciadas (os)/judicialmente, ensino médio completo/superior incompleto, fumantes, que não consomem bebidas alcoólicas abusivamente, consomem frutas três vezes ou mais ao dia e que consideram seu estado de saúde regular. Os resultados do estudo apontam que a depressão é uma doença que incide mais significativamente na população em idade produtiva e fornece evidências sobre fatores associados, alguns potencialmente modificáveis, o que poderá contribuir para o planejamento de políticas públicas.(AU)

The depression is characterized as a multifactorial disorder of the affective area or from the mood, exerts functional impact and involves innumerable aspects of the biological, psychological and social order. The depression currently represents a significant public health problem. The research was developed with the objective of analyzing the relationship between the lifestyle of the economically active population and the prevalence of the depression. It is an empirical analysis developed with secondary data, under a quantitative approach, having as unit of analysis the Northeast Region. Poisson Regression descriptive statistics were performed Poisson regression in the bi and multivariate analyzes to test the association between the response variable and explanatory variables. Poisson Regression descriptive statistics were performed in the bi and multivariate analyzes to test the association between the variable response and explanatory. The prevalence of depression for the population of the Northeast Region, in the age group of 18 years or more, was 5.6%. The variables that in the final multivariate model presented themselves as factors associated to the risk of depression were women, in a age grouo of 40-59 years, separated or judicially divorced, complete high school / incomplete university, smokers who do not consume alcoholic beverages abusively, consume fruit three times or more a day and that consider their health condition as regular. The results of the study indicate that depression is a disease that affects more significantly the population of productive age and provides evidence on associated factors, some potentially modifiable, what will may contribute to the planning of public policies.(AU)

Cortical spreading depression in migraine-time to reconsider? / Depressão alastrante cortical na enxaqueca – hora de reconsiderar?

New evidence concerning the pathophysiology of migraine has come from the results of therapeutic transcranial magnetic stimulation (tTMS). The instantaneous responses to single pulses applied during the aura or headache phase, together with a number of other observations, make it unlikely that cortical spreading depression is involved in migraine. tTMS is considered to act by abolishing abnormal impulse activity in cortical pyramidal neurons and a suggestion is made as to how this activity could arise.

Novas evidências referentes à fisiopatologia da enxaqueca são o resultado de estimulação magnética transcraniana terapêutica (tTMS). As respostas imediatas a pulsos simples aplicados durante as fases de aura ou de cefaleia, em associação a diversas outras observações, tornam improvável a ideia de que a depressão alastrante esteja envolvida na enxaqueca. Considera-se que tTMS tenha sua ação abolindo atividade anormal de impulsos em neurônios corticais piramidais, sugerindo que esta atividade tenha um papel desencadeante.

Aristides Leão: a birth centennial homage with comments on his spreading depression / Aristides Leão: homenagem ao centenário de nascimento com comentários sobre sua depressão alastrante

The year of 2014 is the birth centenary of Aristides Azevedo Pacheco Leão (1914-1993), and also marks seventy years of the publication of his discovery of the novel electrophysiological phenomenon, named by him “spreading depression” (SD), soon designated “Leão’s wave” or “Leão’s spreading depression”. This was a remarkable scientific milestone, and the author must be celebrated for this achievement, as the studies he triggered proceeded worldwide, with new concepts, as spreading depolarization, until the present days. Robust experimental and clinical evidence emerged to suggest that these and related electrophysiological phenomena are involved in the mechanisms of migraine aura, acute cerebrovascular diseases, traumatic brain injury, transient global amnesia, epileptic seizures, and their pathophysiological characteristics come to offer new therapeutic perspectives. He was a remarkable and complex personality, and the authors remit the readers to a paper where his personal life is contemplated.

O ano de 2014 é o centenário de nascimento de Aristides Azevedo Pacheco Leão (1914-1993), e também assinala setenta anos da publicação de sua descoberta, que ele denominou “depressão alastrante” (DA), logo designada “onda de Leão” ou “depressão alastrante de Leão”. Foi um notável marco científico e o autor deve ser celebrado por esse feito, considerando que estudos que desencadeou continuaram no mundo todo, com novos conceitos, como a despolarização alastrante, até os dias atuais. Evidência experimental e clínica robusta emergiram sugerindo que esses fenômenos eletofisiológicos e outros relacionados encontram-se envolvidos nos mecanismos da aura da enxaqueca, doenças cerebrovasculares agudas, lesão cerebral traumática, amnésia global transitória, crises epiléticas, sendo que suas características fisiopatológicas vêm oferecer novas perspectivas terapêuticas. Foi uma personalidade complexa e notável, e os autores remetem os leitores para um artigo no qual sua vida pessoal é contemplada.

Brimonidine tartrate effect on retinal spreading depression depends on Müller cells / O efeito do tartarato de brimonidina sobre a depressão alastrante retiniana depende das células de Müller

Objective: Demonstrate the Brimonidine effect over Retinal Spreading Depression (SD). Brimonidine is an alpha-2–adrenergic receptor agonist, used in the management of glaucoma. Alpha2-agonists have been shown to be neuroprotective in various experimental models, however the molecular and cellular targets leading to these actions are still poorly defined. The SD of neuronal electric activity is a wave of cellular massive sustained depolarization that damages the nervous tissue. Local trauma, pressure, ischemic injuries and other chemical agents as high extracellular potassium concentration or glutamate, can trigger SD, leading to exaggerated focal electrical followed by an electrical silence. Methods: Using chicken retina as model, we performed alpha2-receptor detection by Western Blotting and Immunohistochemistry. After that we obtained electrical signals of SD by microelectrodes on retina in the absence or presence of Brimonidine. For in vivo visualization we observed retina with optical coherence tomography on normal state, with SD passing, and with SD + Brimonidine. Results: Our data demonstrated that: (1) alpha2-adrenergic receptors are present in Müller cells, (2) the treatment with Brimonidine decreases the SD‘s velocity as well as the voltage of SD waves and (3) OCT revealed that SD creates a hyper reflectance at inner plexiform layer, but on retinal treatment with brimonidine, SD was not visualized. Conclusions: Our study about brimonidine possible pathways of neuroprotection we observed it reduces SD (a neuronal damage wave), identified a new cellular target – the Müller cells, as well as, firstly demonstrated SD on OCT, showing that the inner plexiform layer is the main optically affected layer on SD. .

Objetivo: Demonstrar o efeito do Tartarato de Brimonidina, um alfa2-agonista usado no manejo do glaucoma, sobre a depressão alastrante (DA) retiniana. Esses agonistas têm demonstrado ser neuroprotetores em vários modelos experimentais, contudo seus alvos celulares e moleculares continuam indefinidos. A DA da atividade elétrica neuronal é uma onda de despolarização celular massiva e sustentada que leva ao dano no tecido nervoso. Trauma local, pressão, isquemia e outros agentes químicos como o aumento do potássio extracelular e o glutamato podem disparar a DA, levando a uma atividade elétrica exagerada seguida de silêncio elétrico. Métodos: Usando a retina de pinto como modelo, realizamos a detecção do alfa2-receptor por Western Blotting e ensaio Imunohistoquímico. Após isso, obtivemos os sinais elétricos da DA através de microeletrodos inseridos na retina durante sua passagem na presença ou ausência de Brimonidina. Para visualização do tecido utilizamos o tomógrafo de coerência optica (OCT), analisando como é a retina no seu estado de repouso, durante a passagem da DA, e a DA + brimonidina. Resultados: Nossos dados demonstraram que: (1) os receptores alfa adrenérgicos presentes na retina são do subtipo-2A e estão localizados nas células de Müller; (2) o tratamento com Brimonidina diminui a velocidade e a voltagem da onda de DA; (3) A OCT demonstrou que a DA retiniana possui um sinal óptico de maior reflectância na camada plexiforme interna, fato não observado quando foi associada à Brimonidina. Conclusão: A Brimonidina foi capaz de reduzir a DA (uma onda de lesão neuronal) e identificamos um novo possível alvo celular – a célula de Müller e demonstramos pela primeira vez uma OCT da DA, visualizando a camada plexiforme interna como a mais afetada opticamente pelo fenômeno. .

Persistência de imagem de hiperintensidade no hipocampo após episódio de amnésia global transitória / Persistence of hyperintensity image in the hippocampus after an episode of transient global amnesia

A patogenia da amnésia global transitória (AGT) continua obscura. Estudos recentes demonstraram que, em alguns pacientes, a sequência de difusão (DWI) da ressonância magnética pode revelar apresença de sinal pequeno e pontual hipersinal no hipocampo, após a fase aguda do episódio. Esse sinal é principalmente visualizado nas primeiras 6 horas do início do evento, sendo 114 horas o tempo máximo que foi registrado até o momento. Estamos apresentando um caso em que essa imagem persistiu por 11 dias após o episódio. Discutem-se as conhecidas causas, as teorias da patogenia da AGT e a possível conexão entre um efeito vascular e a depressão alastrante, como relatada na enxaqueca com aura.

The pathogenesis of transient global amnesia (TGA) remains obscure.Recent studies revealed that small and punctate signal on diffusion-weighted imaging (DWI) in the hippocampus after the post-acute phase. This signal is mainly seen in the first 6 hours of the onset of the event, and so far the maximum time registered was 114 hours. We present one case where this image persisted for 11 days after the episode. Known causes, theories on pathogenesis of TGA and a possible relation between a vascular mechanism and the spreading depression, as reported in migraine with aura, are discussed.

Migraine With Aura Presenting Reversible Delayed Perfusion

It is believed that migrainous aura is correlated with cortical spreading depression and spreading benign oligemia. A 54-year-old female with migraine with aura presented with left hemianopia preceding pulsating headache. Perfusion-weighted images revealed delayed contrast arrival to the right occipital lobe and nearly normal relative cerebral blood volume images, indicating benign oligemia. Follow-up perfusion-weighted images revealed resolution of the perfusion abnormalities. We report herein a case of migraine with aura presenting with reversible delayed perfusion in the right occipital lobe on perfusion-weighted images.

Signos de liberación cortical en pacientes con esquizofrenia, trastornos depresivos, trastorno afectivo bipolar, demencia y enfermedad cerebrovascular / Cortical Release Signs in Patients with Schizophrenia, Depressive Disorders, and Bipolar Affective Disorder

Resumen Introducción y objetivos: Determinar la presencia de signos de liberación cortical, asociada a daño de sustancia blanca, es un método clínico de fácil realización. El objetivo es deter minar la presencia de signos de liberación cortical en pacientes con enfermedades mentales y enfermedad cerebrovascular y determinar su utilidad clínica, dado que indica daño cortical. Material y métodos: Se realiza búsqueda de signos de liberación cortical en pacientes hospitalizados en clínica psiquiátrica y hospital general con diagnósticos de trastorno afectivo bipolar (40), depresión (37), esquizofrenia (33), enfermedad cardiovascular (33) y demencia (37). Resultados: Los signos de liberación cortical no tienen igual importancia en la determinación de daño cortical; por ejemplo, se encontró reflejo glabelar en todos los grupos; el de paratonía, especialmente en el grupo con esquizofrenia, y más signos, en el grupo de pacientes con demencia. Conclusiones: Se formula que estos signos implican daño de sustancia blanca subcortical; la aparición de estos signos supone la necesidad de seguimiento de pacientes con diagnósticos de trastorno afectivo bipolar, depresión y esquizofrenia.

Abstract Background and objectives: Determining the presence of cortical release signs associated with white matter damage, is a clinically easy method to perform. The objective of this study is to determine the presence of cortical release signs in patients with mental illnesses and cerebrovascular disease, as well as its clinical usefulness, given that it indicates cortical damage. Material and methods: A review was made of cortical release signs in patients hospitalized in clinical psychiatry and general hospitals with bipolar affective disorder (40), depression (37), schizophrenia (33), cardiovascular disease (33) and dementia (37). Results: The signs of cortical release do not have the same importance as cortical damage. For example, the glabellar reflex was found in all the groups, that of paratonia, particularly in the group with schizophrenia, and others signs in the group of patients with dementia. Conclusions: It is suggested that these signs imply subcortical white matter damage. The appearance of these signs shows the need for a follow up of patients diagnosed with bipolar affective disorder, depression and schizophrenia.

Clinical Efficacy of Acute Monitoring Cortical Activity Using Subdural Strip Electrode after Decompressive Craniectomy / 대한신경손상학회지

OBJECTIVE: Decompressive craniectomy is widely used in cases of uncontrolled intracranial hypertension, including traumatic brain injury or acute stroke. Physiological monitorings, such as intracranial pressure or electroenecephalography (EEG) are critical for patients in the acute phase. We retrospectively reviewed our experience of continuous electrocorticography (ECoG) monitoring by subdural strip electrode in patients who performed decompressive craniectomy and assessed its clinical efficacy. METHODS: Patients who underwent decompressive craniectomy because of severe intracranial hypertension were included. 4 Channel strip electrodes were inserted on the frontal cortex before closure. 24-hour continuous monitoring of ECoG was done to identify abnormal electrical activity. The level of consciousness was assessed according to Glasgow Coma Scale (GCS). In patients with malignant intracranial hypertension, barbiturate coma therapy was considered. RESULTS: Fifteen patients (9 men and 6 women) were included and the mean age was 55.7 years (from 17 to 80). The initial mean GCS score was 7.9 (from 3 to 14). In six out of fifteen patients, abnormal spike activities were identified, and one of these six patients was diagnosed as nonconvulsive status epilepticus (NCSE). Cortical spreading depression (CSD) was suspected in five. Three patients underwent barbiturate coma therapy and ECoG monitoring of these patients showed typical burst suppression pattern, which was used for indicator of therapeutic level. The mean duration of strip electrode and ECoG monitoring was 3.5 days, and there was no complication. CONCLUSION: Continuous ECoG monitoring using subdural strip electrode was useful to detect abnormal brain activity in the acute period after decompressive craniectomy.

Pathophysiology of Vestibular Migraine / 대한평형의학회지

Vestibular migraine (VM) is an increasingly recognized cause of episodic recurrent vertigo. However, the pathophysiology of VM is still a matter of speculation. An understanding of the relationship between migraine and the vestibular system increases knowledge of the pathogenesis of both migraine and vertigo. The pathophysiology of VM has been known to be related to cortical spreading depression, neurotransmitters (i.e., serotonin, noradrenaline, dopamine, calcitonin gene-related peptide) and calcium ion channel disorder. Moreover, VM is related with Meniere's disease, benign paroxysmal positional vertigo, motion sickness, cerebellar dysfunction, or comorbid psychotic disorder. This review refines recently proposed pathophysiological concept for VM and relationships between migraine and other related disorders.

Depressão alastrante cortical e seu possível papel na lesão neuronal subsequente à hemorragia subaracnóide aneurismática / The role of cortical spreading depolarizations in delayed cerebral ischemia after aneurysmal subarachnoid hemorhage

Isquemia cerebral tardia (delayed cerebral ischemia; DCI)é a principal causa potencialmente tratável de mortalidade e incapacidade em pacientes com hemorragia subaracnóide aneurismática (HSA). No entanto, não existe tratamento eficaz para esta condição até o momento. A recente demonstração da falta de resposta clínica à reversão farmacológica do espasmo arterial após HSA estimulou uma reavaliação dos conceitos fisiopatológicos na DCI que segue a HSA,que foram por muito tempo creditados ao espasmo arterial observado em doentes com HSA. Desde a demonstração de resultados eletrocorticográficos de depressão cortical generalizada(“cortical spreading depressions”, CSD) em pacientes com HSA, um crescente interesse foi despertado sobre opapel destes fenômenos na fisiopatologia da DCI observados em pacientes com HSA. Quando induzida em um cérebro saudável, a CSD está associada com aumento do fluxo sanguíneo cerebral, facilitando a distribuição de substratos de energia necessários para repolarização celular cerebral.Em um cérebro lesado, no entanto, CSDs estão associados a uma redução do fluxo sanguíneo cerebral, que, no contexto de aumento das necessidades da energia, leva à falha de energia e hipóxia, acentuando a gravidade da lesão cerebral. Esta resposta inversa hemodinâmica à CSD foi descoberta pela primeira vez em um modelo animal, replicando as condições de HSA e, posteriormente, demonstrado em pacientes com HSA. A isquemia leva à escassez de substratos energéticos e propagação da hipóxia, resultando em lesões corticais, e podem explicar os padrões de lesão, semelhantemente ao que ocorre em pacientes com HSA. Estas observações sugerem que o déficit de energia produzida por CSD é um fator chave na patogênese dos DCI observados como resultado da HSA.Este artigo detalha as principais características de CSDs e sua potencial relevância na fisiopatologia das complicações isquêmicas da HSA.

Delayed cerebral ischemia (DCI) is the leading potentially treatable cause of mortality and disability in patients with aneurysmal subarachnoid hemorrhage (SAH). However, to date there is no effective treatment for this entity. The recently demonstrated lack of clinical response to pharmacologic reversal of arterial spasm as a result of SAH has spurred a reassessment of the pathophysiological concepts on DCI that follows SAH.DCI was long believed the consequence of the angiographically visible arterial spasm observed in patients with SAH. Since themeasurement of cortical spreading depolarizations (CSD) inpatients with SAH, increasing evidence has suggested a role for these phenomena in the pathophysiology of DCI. When induced in a healthy brain, CSDs are associated with an increase in regional cerebral blood flow that facilitates the delivery of the necessary energy substrates for cellular repolarization. Ina brain that has been injured, however, CSDs can induce microvascular constriction, or cortical spreading ischemia. This inverse hemodynamic response to CSD was first discovered in an animal model replicating the conditions following SAH, and later demonstrated in patients with SAH. The spreading ischemia leads to energy substrates shortage and hypoxia, resulting in cortical lesions, and may explain similar lesion patterns which occur in SAH patients. This review describes the salient characteristics of CSD and its potential relevance in the pathophysiology, monitoring, and treatment of ischemic complications following SAH.

Migraine-Associated Vertigo and Dizziness as Presenting Complaint in a Private General Medical Practice

Migraine-associated vertigo (MV) remains a developing entity because accepted diagnostic criteria are unavailable. Patients present with debilitating dizziness without experiencing headache; and are often misdiagnosed as anxious. The condition is manageable in primary care without the need for neurological referral. The aim of this study was to investigate the prevalence of MV and migraine-associated dizziness (MD) as presenting complaints. Methods: Patients presented with dizziness probably or definitely associated with migraine history based on the criteria of the International Headache Society. Patients with other vestibulopathies and medical conditions were excluded. Patients were evaluated over a period of nine months. Seven hundred and seventeen patients were examined. The numbers of patients were recorded as a percentage of the population visiting a general practitioner. Response to migraine prophylactic medications was regarded as supporting evidence of the diagnosis. Response was regarded as a complete resolution of symptoms. Results: Of the 717 patients seen; 12 were identified as having probable or definite MV. Five patients were treated with migraine prophylactic medications; namely amitriptyline 25 mg nocte and/or sodium valproate CR 300 mg bd; and all showed a response to the treatment. Conclusions: We conclude that the prevalence of MV as presenting complaint may be as high as 1.67. This figure does however not reflect the total patient population that suffers from the condition - this figure may be much higher. Of those patients treated for MV the response was 100; further supporting the diagnosis. MV is a relevant complaint that is often misdiagnosed as psychogenic in origin

Depresiones corticales propagadas y su posible rol en la fisiopatología del daño neuronal subsecuente a la hemorragia subaracnoidea / Cortical spreading depressions and their role in the pathophysiology of neuronal damage subsequent to aneurysmal subarachnoid hemorrhage

El vasoespasmo cerebral es la principal causa potencialmente tratable de mortalidad e incapacidad en pacientes que sufren hemorragia subaracnoidea aneurismática (HSA). Sin embargo, a la fecha no existe un tratamiento eficaz para el mismo. La reciente demostración de la falta de respuesta clínica a la reversión farmacológica del espasmo arterial a consecuencia de HSA ha obligado un replanteo de los fundamentos fisiopatológicos de los déficits neurológicos isquémicos tardíos (“delayed ischemic neurologic déficit”, DIND) a consecuencia de HSA, los cuales se creían en relación al espasmo arterial observado en pacientes con HSA. Desde la demostración de hallazgos electrocorticográficos de depresión cortical propagada (“cortical spreading depression”, CSD) en pacientes con HSA, un interés creciente se ha despertado respecto del rol de estos fenómenos en la fisiopatología de los DIND observados en pacientes con HSA. Cuando inducidas en un cerebro saludable, las CSD se asocian con un aumento del flujo sanguíneo cerebral, facilitando la entrega del cerebro de los sustratos energéticos necesarios. En un cerebro que ha sido lesionado, sin embargo, la CSD se asocia con una reducción en flujo sanguíneo cerebral, lo cual, en el contexto de un aumento de las necesidades de energía, conduce a la insuficiencia energética y la hipoxia, empeorando así el daño cerebral. Estas observaciones sugieren que el déficit de energía producida por la CSD es un factor clave en la patogénesis de los DIND observados a consecuencia de HSA. Este resumen detalla características sobresalientes de las CSD y su potencial relevancia en la fisiopatología del vasoespasmo.

Cerebral vasospasm is the leading potentially treatable cause of mortality and disability in patients with aneurysmatic subarachnoid hemorrhage (SAH). However, to date there is no effective treatment for this entity. The recently demonstrated lack of clinical response to pharmacologic reversal of arterial spasm as a result of SAH has spurred a reassessment of the pathophysiological concepts on delayed ischemic neurologic deficits (DIND) that follow SAH, which were long believed the effect of the arterial spasm observed in patients with SAH. Since the discovery of electrocorticographic cortical spreading depressions (CSD) in patients with SAH, increasing interest has been shown on the role of these phenomena in the pathophysiology of DIND observed in patients with HSA. When induced in a healthy brain, CSD are associated with an increase in cerebral blood flow by facilitating the delivery of the necessary energy substrates. In a brain that has been injured, however, CSD are associated with a reduction in cerebral blood flow, which, in the context of increased energy requirements leads to energy shortage and hypoxia, thus worsening brain damage. These observations suggest that the energetic deficit produced by the CSD is a key factor in the pathogenesis of DIND observed as a result of HSA. This review details striking characteristics of CSD and their potential relevance in the pathophysiology of vasospasm.

Acute tryptophan administration impairs cortical spreading depression propagation in REM sleep deprived and non-deprived adult rats

The enhanced availability of tryptophan in the brain, as a consequence of exogenous tryptophan administration, can increase neuronal serotonin synthesis and this can interfere with brain function. REM sleep deprivation (D) constitutes another external factor that can change brain excitability, facilitating, in some cases, the manifestation of neurological diseases like epilepsy. Here we used cortical spreading depression (CSD) as a neurophysiological parameter to investigate the effects of a single L-tryptophan intraperitoneal injection combined or not with 72h D-condition (water-tank technique) in rats. A 1h baseline CSD-recording was performed under urethane+chloralose (1g/kg + 40mg/kg) anesthesia and revealed increased CSD propagation velocities in D rats, as compared with non-deprived (ND), or pseudo-deprived (Pseudo) controls. After the baseline CSD recording, L-tryptophan was immediately injected (125 mg/kg ip, dissolved in water at pH about 3) and this was followed by a significant decrease of CSD propagation velocities, as compared to the baseline values in the same animals of the Pseudo, ND and D condition. In an additional control group (ND rats injected with the vehicle), no CSD propagation change was seen. Our findings indicate an important acute antagonistic influence of tryptophan on CSD propagation, which is not affected by REM sleep deprivation. We suggest that this tryptophan effect may be due to a serotonin-mediated action, probably caused by increased serotonin synthesis as a consequence of enhanced tryptophan availability in the brain.

Effect of cortical spreading depression on spontaneous firing activities of STN neurons in rats / 中国应用生理学杂志

<p><b>AIM</b>To observe the effect of cortical spreading depression (CSD) on the spontaneous firing activities of neurons of subthalamic nucleus (STN) in normal and model rat of Parkinson's disease (PD).</p><p><b>METHODS</b>Extracellular recording was used to research the neuronal electric activities in subthalamic neurons. The changes of the discharge rates of subthalamic neurons were observed in control and PD rats after intracortical microinjection of KCl solution.</p><p><b>RESULTS</b>The discharge rates of subthalamic neurons in control and PD rats were (9.78 +/- 0.71) Hz and (23.81 +/- 1.08) Hz, respectively. The discharge rate of PD rats was increased significantly when compared with those of the control rats and the percentage of neurons discharging in bursts was obviously higher than those of control rats (P < 0.01). After a long latent period secondary to intracortical injection of KCl solution, the discharge rates in both group of subthalamic neurons were decreased apparently, then recovered slowly.</p><p><b>CONCLUSION</b>The discharge rate and bursting pattern are increased in PD rats and these abnormal activities can be improved by cortical depression. This result indicates that the changes in cortical excitability may be one of the factors increasing the activity of STN in PD.</p>

The Serum Concentration of Matrix Metalloproteinase-9 in Childhood Migraine

PURPOSE: Migraine is a common neurological disorder, but the mechanism has not yet been apparently discovered. Recent studies have found that migrainous headache comes from the hemodynamic changes based on the cortical spreading depression and matrix metalloproteinase(MMP)-9 has an important role in this phenomenon. The aim of this study is to investigate the significance of the serum concentration of MMP-9 in children with migraine. METHODS: Among 33 children who visited the headache clinic, from June 2004 to August 2004 we identified and analyzed the clinical findings of 17 patients, who were diagnosed as migraine or tension-type headache. Also we selected 9 children as a healthy control group. The serum concentrations of MMP-9 from all of those were obtained via ELISA kits. RESULTS: The mean duration of headache was 1.3 years in the migraine group. Also, the frequency of migraine is as follows:everyday in 4 patients and more than once during weekdays in 5 patients. The character of headache was throbbing in 8 patients out of 9 patients with migraine. There were no significant differences found in the serum concentrations of MMP-9 between the control group and the migraine group. The serum concentrations of MMP-9 were significantly high, of those who had frequent attacks of migrainous headache. CONCLUSION: The serum concentrations of MMP-9 in the migraine group were not significantly high compared with those in the control group. However, the levels were high from those who complained of migraine frequently. This study suggests that the serum concentration of MMP-9 is not high during a normal period but increases when migraine occurrs.