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Abstract There are no clinical interventions to prevent post-injury epilepsy, a common and devastating outcome after brain insults. Epileptogenic events that run from brain injury to epilepsy are poorly understood. Previous studies in our laboratory suggested Proechimys, an exotic Amazonian rodent, as resistant to acquired epilepsy development in post-status epilepticus models. The present comparative study was conducted to assess (1) stroke-related brain responses 24-h and 30 days after cortical photothrombosis and (2) post-stroke epilepsy between Proechimys rodents and Wistar rats, a traditional animal used for laboratory research. Proechimys group showed smaller volume of ischemic infarction and lesser glial activation than Wistar group. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Electrophysiological signaling changes assessed by cortical spreading depression, in vitro and in vivo, showed that Wistar’s brain is most severely affected by stroke. Chronic electrocorticographic recordings showed that injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Science gains insights from comparative studies on diverse species. Proechimys rodents proved to be a useful animal model to study antiepileptogenic mechanisms after brain insults and complement conventional animal models.

Abstract Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS.

A classic method to evaluate autonomic dysfunction is through the evaluation of heart rate variability (HRV). HRV provides a series of coefficients, such as Standard Deviation of n-n intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD), which have well-established physiological associations. However, using only electrocardiogram (ECG) signals, it is difficult to identify proper autonomic activity, and the standard techniques are not sensitive and robust enough to distinguish pure autonomic modulation in heart dynamics from cardiac dysfunctions. In this proof-of-concept study we propose the use of Poincaré mapping and Recurrence Quantification Analysis (RQA) to identify and characterize stochasticity and chaoticity dynamics in ECG recordings. By applying these non-linear techniques in the ECG signals recorded from a set of Parkinson’s disease (PD) animal model 6-hydroxydopamine (6-OHDA), we showed that they present less variability in long time epochs and more stochasticity in short-time epochs, in their autonomic dynamics, when compared with those of the sham group. These results suggest that PD animal models present more “rigid heart rate” associated with “trembling ECG” and bradycardia, which are direct expressions of Parkinsonian symptoms. We also compared the RQA factors calculated from the ECG of animal models using four computational ECG signals under different noise and autonomic modulatory conditions, emulating the main ECG features of atrial fibrillation and QT-long syndrome.

SARS-CoV-2 vaccinations are not free from side effects. Usually, they are mild or moderate but occasionally severe. One of these severe side effects is Guillain-Barré syndrome (GBS). This review summarizes and discusses GBS as a side effect of SARS-CoV-2 vaccinations (SCoVaG) based on recent research reports. Altogether, nine articles reporting 18 patients with SCoVaG were identified and one more report on another patient is under review. The age for the studies ranged between 20-86y. Nine patients were male, and ten were female. In all 19 patients, SCoVaG developed after the first dose of the vaccine. The Astra Zeneca vaccine was used in fourteen patients, the Pfizer vaccine in four patients, and the Johnson & Johnson vaccine was applied in one patient. The latency between vaccination and onset of GBS ranged from 3h to 39d. The treatment of SCoVaG included IVIGs (n=13), steroids (n=3), or no therapy (n=3). Six patients required mechanical ventilation. Only a single patient recovered completely and partial recovery was achieved in nine patients. In conclusion, GBS may develop time-linked to the first dose of a SARS-CoV-2 vaccination. Though a causal relationship between SARS-CoV-2 vaccinations and SCoVaG remains speculative, more evidence is in favour than against it.

Abstract In this letter we raise several concerns regarding the interesting article by Walter and Krämer about rhomb-encephalitis as a complication two months after the vaccination with an mRNA-based SARS-CoV_2 vaccine. The causal link between the vaccination and encephalitis remained unproven, a SARS-CoV-2 infection, Bickerstaff encephalitis were not excluded, the MRI rather suggests brainstem-encephlaitis than pure rhomb-encephalitis, and the cerebro-spinal fluid was not investigated for cytokines or glial markers. Neurologists are called to make all available effort to convincingly evaluate the etiology and the pathophysiological background of an undetermined condition.

Coronavirus disease (COVID-19) usually starts with pulmonary signs and symptoms. However, in some cases, the initial clinical presentations are extrapulmonary. This literature review aimed at summarizing and discussing the extrapulmonary onset manifestations of COVID-19. The most frequent initial extrapulmonary manifestations include hypogeusia, hyposmia, non-specific abdominal symptoms, corneal congestion, and deep venous thrombosis. Several rarer extrapulmonary manifestations in locations such as the brain, peripheral nerves, muscles, eyes, ears, myocardium, intestines, skin, or vessels have been additionally reported as onset presentations of COVID-19. In conclusion, it is crucial for clinicians and health care providers to consider extrapulmonary presentations at the onset of COVID-19 to avoid overlooking the infection and contributing to the spread of the disease.

Males of Proechimys guyannensis, a rodent living in the Amazon rainforest are studied in biomedical research because of their antiepileptogenic mechanism. Females are usually taken from experimental designs, because of limited data of this sex. This study aimed to characterize the estrous cycle to include females together with males in research in a more balanced approach. The estrous cycle of P. guyannensis based through exfoliative cytology, determination of the vaginal occlusion membrane state, and hormonal analysis. In this study, cytological analyses of vaginal smears were performed for three months, three times a day. The observed length of the estrous cycle was 247 ± 81 h (mean ± SD) with a reproductive phase of 27.08 ± 17.39 h (estrus stage). We observed a frequent presence of both the open and closed states of the vaginal membrane in the estrus stage (fertile period) although only the open stage is a prerequisite for successful copulation. High levels of progesterone and estradiol were detected in proestrus. Levels of follicle-stimulating hormone peaked at the estrus stage. These data will establish the parameters and subsidies to set the grounds for future research either for investigating the biology of this species or to use P. guyannensis in research that previously excluded females. Information regarding female Proechimys is relevant to not only describe the species but also explain the interaction between sex hormones and physiological responses. Moreover, the present results will enhance rigor and reproducibility in preclinical studies. In conclusion, P. guyannensis reproductive cycles can occur spontaneously and cyclically independent of mating stimulation and the high levels of FSH in the estrus stage, suggest that ovulation occurs in the late phase of the estrus.

Abstract Human hippocampal slice preparations from patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) are excellent material for the characterization of epileptiform-like activity. However, it is still unknown if hippocampal regions as cornu Ammonis (CA) 1, CA3 and CA4, generate population epileptiform-like activity. Here, we investigated epileptiform activities of the subiculum, CA1, CA2, CA3, CA4 (induced by elevation of extracellular potassium concentration) and the dentate gyrus (induced with hilar stimulation and elevation of potassium concentration) from sclerotic hippocampi of patients with drug-resistant TLE. Five types of epileptiform-like activity were observed: interictal-like events; periodic ictal spiking; seizure-like events; spreading depression-like events; tonic seizure-like events and no activity. Different susceptibilities to generate epileptiform activity among hippocampal regions were observed; the dentate gyrus was the most susceptible region followed by the subiculum, CA4, CA1, CA2 and CA3. The incidence of epileptiform activity pattern was associated with specific regions of the hippocampal formation. Moreover, it was observed that each region of the hippocampal formation exhibits frequency-specific ranges in each subfield of the sclerotic human tissue. In conclusion, this study demonstrates that epileptiform-like activity may be induced in different regions of the hippocampal formation, including regions that are severely affected by neuronal loss.

Background: Diverse forms of long-term potentiation (LTP) have been described, but one of the most investigated is encountered in the glutamatergic synapses of the hippocampal cornu Ammonis (CA1) subfield. However, little is known about synaptic plasticity in wildlife populations. Laboratory animals are extremely inbred populations that have been disconnected from their natural environment and so their essential ecological aspects are entirely absent. Proechimys are small rodents from Brazil’s Amazon rainforest and their nervous systems have evolved to carry out specific tasks of their unique ecological environment. It has also been shown that long-term memory duration did not persist for 24-h in Proechimys, in contrast to Wistar rats, when both animal species were assessed by the plus-maze discrimination avoidance task and object recognition test.Methods: In this work, different protocols, such as theta burst, single tetanic burst or multiple trains of high frequency stimulation (HFS), were used to induce LTP in hippocampal brain slices of Proechimys and Wistar rats.Results: A protocol-independent fast decay of early-phase LTP at glutamatergic synapses of the CA1 subfield was encountered in Proechimys. Long-term depression (LTD) and baseline paired-pulse facilitation (PPF) were investigated but no differences were found between animal species. Input/output (I/O) relationships suggested lower excitability in Proechimys in comparison to Wistar rats. Bath application of d-(-)-2-amino-5-phosphonopentanoicacid (D-AP5) and CNQX prevented the induction of LTP in both Proechimys and Wistar. However, in marked contrast to Wistar rats, LTP induction was not facilitated by the GABAA antagonist in the Amazon rodents, even higher concentrations failed to facilitate LTP in Proechimys. Next, the effects of GABAA inhibition on spontaneous activity as well as evoked field potentials (FPs) were evaluated in CA1 pyramidal cells. Likewise, much lower activity was detected in Proechimys brain slices in comparison to those of the Wistar rats.Conclusions: These findings suggest a possible high inhibitory tone in the CA1 network mediated by GABAA receptors in the Amazon rodents. Currently, neuroscience research still seeks to reveal molecular pathways that control learning and memory processes, Proechimys may prove useful in identifying such mechanisms in complement to traditional animal models.

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys, contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys. Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated.

This letter was written in response to: Giron C, Roze E, Degos, B, Méneret A, Jardel C, Lannuzel A, et al. Adult-onset generalized dystonia as the main manifestation of MEGDEL syndrome. Tremor Other Hyperkinet Mov. 2018; 8. doi: 10.7916/D8VM5VBQ

It is extremely difficult to estimate the occurrence of sudden unexpected death in epilepsy (SUDEP). On the other hand, discovering and carefully evaluating new risk factors that may contribute to the onset of cardiovascular abnormalities in people with refractory epilepsy may prevent fatal events in these individuals. In this context, we should not ignore that urban air pollution is a leading problem for environmental health and is able to cause serious cardiovascular dysfunctions that culminate in sudden death. In this regard, we aimed to determine whether environmental exposure to air pollution is an aggravating event for SUDEP.

Intellectual disability is a prevalent form of cognitive impairment, affecting 2-3% of the general population. It is a daunting societal problem characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social and practical adaptive skills. Intellectual disability is a clinically important disorder for which the etiology and pathogenesis are still poorly understood. Moreover, although tremendous progress has been made, pharmacological intervention is still currently non-existent and therapeutic strategies remain limited. Studies in humans have a very limited capacity to explain basic mechanisms of this condition. In this sense, animal models have been invaluable in intellectual disability investigation. Certainly, a great deal of the knowledge that has improved our understanding of several pathologies has derived from appropriate animal models. Moreover, to improve human health, scientific discoveries must be translated into practical applications. Translational research specifically aims at taking basic scientific discoveries and best practices to benefit the lives of people in our communities. In this context, the challenge that basic science research needs to meet is to make use of a comparative approach to benefit the most from what each animal model can tell us. Intellectual disability results from many different genetic and environmental insults. Taken together, the present review will describe several animal models of potential intellectual disability risk factors.

Of the many risk factors suggested for sudden unexpected death in epilepsy (SUDEP), higher frequency of seizures is a very consistent issue. Following this reasoning, it has been established that hemodialysis-associated seizure is a complication of dialysis procedure. Based on these facts, this study investigated a possible association between cardiovascular abnormalities and SUDEP among patients with chronic renal insufficiency in regular hemodialysis program. For that, a retrospective medical history of 209 patients was reviewed to investigate the occurrence of convulsive seizures and EKG abnormalities during dialytic program. Three patients presented generalized tonic-clonic seizures, one had partial seizure with secondary generalization, and one presented unclassified seizure. Any EKG abnormalities and SUDEP event were found in all patients evaluated. In conclusion, the present findings demonstrated uncommon the occurrence of seizures and also SUDEP. Probably, the main justification to not allow us to demonstrated a direct relation between SUDEP and cardiovascular diseases in hemodialysis are the reduced number of cases examined.Um dos principais fatores de risco para a morte súbita e inesperada na epilepsia (SUDEP) é a alta freqüência de crises epilépticas. Seguindo este raciocínio, tem sido estabelecido que as crises epilépticas associadas à hemodiálise seja uma complicação do procedimento dialítico. Baseado neste fato, este estudo investigou uma possível associação entre anormalidades cardiovasculares e SUDEP nos pacientes com insuficiência renal crônica em um programa regular de hemodiálise. Para isto, um histórico médico retrospectivo de 209 pacientes foi revisado para avaliar a ocorrência de crises epilépticas e possíveis anormalidades no ECG durante o programa de diálise. Três pacientes apresentaram crises tônico-clonica generalizadas, um apresentou crise parcial com generalização secundária e um apresentou crise não-classificada. Não detectamos anormalidades no ECG e ocorrência de SUDEP em todos os pacientes avaliados. Em conclusão, na presente amostra constatou-se como rara a ocorrência de crises epilépticas e SUDEP. Provavelmente, o número reduzido de casos avaliados tenha sido responsável pela não observação de uma relação direta entre SUDEP e as doenças cardiovasculares na hemodiálise.

Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. More than two decades ago, temporal lobe epilepsy was suggested as having been the ''nervous disease'' of Gustave Flaubert, one of the most important French novelists. In these lines, as the circumstances of his death were the subject of fabulous and mysterious speculations, we postulated in this paper that Falubert' death could be due SUDEP phenomenon.A epilepsia é a condição neurológica crônica grave mais comum e a morte súbita em epilepsia (SUDEP) é a mais importante causa de morte diretamente relacionada à epilepsia. Informações sobre fatores de risco para SUDEP são conflitantes, porém, a alta freqüência de crises epilépticas é um fator de risco em potencial. Além disso, os mecanismos causais para SUDEP ainda não estão conhecidos, mas é muito provável que arritmias cardíacas durante e entre as crises epilépticas ou a transmissão da atividade epiléptica para o coração via sistema nervoso autônomo desempenhem um importante papel. Mais de duas décadas atrás, foi proposto que a "doença nervosa" de Gustave Flaubert, um dos mais importantes novelistas franceses, era epilepsia do lobo temporal. Nesse sentido, como a morte de Gustave Flaubert ainda seja motivo de misteriosa especulação, nosso artigo propõe que a mesma poderia estar relacionada ao fenômeno de SUDEP.

Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of seizure-related mortality in people with refractory epilepsy. Several risk factors for SUDEP are described; however, the importance of including low temperatures as risk factor for SUDEP was never explored. Based on this, the aim of this study was to evaluate the heart rate of rats with epilepsy during low temperature exposure. Our results showed that low temperature clearly increased the heart rate of rats with epilepsy. Taken together, we concluded that exposure to low temperatures could be considered important risk factors from cardiovascular abnormalities and hence sudden cardiac death in epilepsy.A morte súbita e inesperada nas epilepsias (SUDEP) é considerada a maior causa de morte em indivíduos com epilepsia refratária. Vários fatores de risco para SUDEP têm sido descritos, no entanto, a inclusão das baixas temperaturas como um possível fator de risco para SUDEP não foi verificada até o momento. Nesse sentido, o objetivo desse estudo foi verificar a freqüência cardíaca de animais com epilepsia expostos as temperaturas baixas. Nossos resultados demonstraram que as baixas temperaturas são capazes de aumentar significativamente a freqüência cardíaca de animais com epilepsia. Dessa forma, concluímos que as baixas temperaturas podem ser consideradas um importante fator de risco de possíveis alterações cardiovasculares e até mesmo morte súbita cardíaca nas epilepsias.

Obstructive sleep apnea (OSA) is a multifactorial sleep disorder associated to increased risk for cardiovascular mortality and morbidity. Several mechanisms were proposed to explain the association between the occurrence of OSA and increased cardiovascular dysfunction. One of the proposed mechanisms is the inflammatory response to OSA mediated especially by tumor necrosis factor (TNF-α). Patients with OSA showed higher plasmatic, serum, and intracellular levels of TNF-α, which may be reduced after apnea treatment with continuous positive airway pressure (CPAP). Considering that TNF-α plays an important role in OSA related cardiovascular morbidity, the present review speculates if there is any preventive measure, besides the use of CPAP, which could minimize the inflammatory process in OSA and consequently the risk of premature death by cardiovascular dysfunctions. Thus, we hypothesized that a possible answer for this question is the nutritional immunology profile, or rather, more precisely by the supplementation with omega-3 fatty acids (omega-3 FAs) for individuals with OSA.

On February 12, 2009, we commemorated the 200th anniversary of Charles Darwin's birth and the 150th anniversary of the publication of the ûrst edition of the "On the origin of species". Only in the sixth edition of the Origin Darwin explicitly stated that natural selection applied to the brain as to all other organs and contemporary epilepsy research plays an interesting role in this scenario. Epilepsy affects approximately 3 percent of the general population and is a complex disease. At least 11 genes have now been described for human epilepsy and over 50 more genes have been identified in animal models of epilepsy. The complex gene to gene interactions and gene-environment interactions may account for epilepsy susceptibility and antiepileptic drug response. Darwin's thoughts on evolution are relevant to understand these gene interactions, contributing to current development of new treatments and prevention of chronic diseases, such as epilepsy.Em 12 de Fevereiro de 2009 nós comemoramos o aniversário de 200 anos de Charles Darwin e os 150 anos da publicação da primeira edição do livro "A Origem das Espécies". Apenas na sexta edição do livro A Origem, Darwin explicitamente definiu que a seleção natural se aplicava ao cérebro, assim como a todos os outros órgãos e as pesquisas contemporâneas em epilepsia tem um papel interessante neste cenário. A epilepsia afeta aproximadamente 3% da população geral e é uma doença complexa. Ao menos 11 genes foram descritos até o momento na epilepsia humana e mais de 50 genes foram identificados em modelos animais de epilepsia. As complexas interações gene-gene e genes-meio ambiente podem estar relacionadas com a susceptibilidade à epilepsia e respostas às drogas antiepilépticas. Os pensamentos de Darwin quanto à evolução são relevantes para a compreensão dessas interações gênicas, contribuindo para o desenvolvimento de novos tratamentos e na prevenção de doenças crônicas, como a epilepsia.

Epilepsy is the commonest serious neurological disorder and individuals with epilepsy are at higher risk of death than the general population and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures play a potential role. The ultimate goal of SUDEP research is to develop methods to prevent it and nutritional aspects such as omega-3 fatty acid deficiency may have an interesting role in this scenario. Omega-3 fatty acids reduce the risk of cardiovascular mortality and are important for treating or preventing some neurological diseases, including epilepsy. A dietary modification or nutritional supplements increasing the ingestion of omega-3 fatty acids may help to ''save the brain".A epilepsia é uma das doenças neurológicas sérias mais comuns e está associada a um maior risco de morte do que o observado na população geral e a morte súbita em epilepsia é uma importante causa de morte relacionada à epilepsia. Os potenciais patomecanismos da morte súbita em epilepsia são desconhecidos, mas é bastante provável que arritmias cardíacas durante ou entre as crises tenham um papel preponderante. O objetivo final das pesquisas em morte súbita em epilepsia é o desenvolvimento de métodos que levem à sua prevenção e aspectos nutricionais, como a deficiência de ômega-3 pode ter um papel interessante neste contexto. A suplementação com ômega-3 reduz o risco de mortalidade de origem cardiovascular e é importante no tratamento e prevenção de algumas doenças neurológicas, incluindo a epilepsia. A modificação dietética ou a suplementação nutricional aumentando a ingesta de ômega-3 pode ajudar a "salvar o cérebro".