Norberto Garcia-Cairasco

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Verified

Norberto verified their affiliation via an institutional email.

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• BSc, MSc, PhD
• Professor (Full) at University of São Paulo

Emerging evidence suggests a bidirectional relationship between Alzheimer’s disease (AD) and epilepsy. In our previous studies, we identified a partial AD-like phenotype associated with central insulin resistance in the Wistar audiogenic rat (WAR), a genetic model of epilepsy. We also found that intracerebroventricular administration of streptozoto...

Background & Objective Alzheimer Disease (AD) patients at multiple stages of disease progression have a high prevalence of seizures. However, whether AD and epilepsy share pathophysiological changes remains poorly defined. In this study, we leveraged high-throughput transcriptomic data from sporadic AD cases at different stages of cognitive impairm...

Introduction Spiders are predators that use their venom to immobilize their prey. These spider toxins are able to affect the central nervous system of mammals. Methods We hypothesized that venom from the tarantula Vitalius platyomma may induce behavioral changes in male Wistar rats. To test this hypothesis, the behavioral effects of venom were inv...

Keywords: Semiology Computational approaches Computer vision Epilepsy phenotyping Quantitative and computational neuroethology A B S T R A C T Seizure events can manifest as transient disruptions in the control of movements which may be organized in distinct behavioral sequences, accompanied or not by other observable features such as altered facia...

Vagus nerve stimulation (VNS) is an adjuvant neuromodulation therapy for the treatment of refractory epilepsy. However, the mechanisms behind its effectiveness are not fully understood. Our aim was to develop a VNS protocol for the Genetic Audiogenic Seizure Hamster from Salamanca (GASH/Sal) in order to evaluate the mechanisms of action of the ther...

Epilepsy is a complex disease mainly defined by the susceptibility to spontaneous recurrent seizures but is also often associated with complex comorbid conditions. Despite the introduction of dozens of new antiseizure medications (ASMs), pharmacoresistance, which affects up to 30% of patients with epilepsy (PWE), remains a significant challenge for...

Since glucose reuptake by neurons is mostly independent of insulin, it has been an intriguing question whether insulin has or not any roles in the brain. Consequently, the identification of insulin receptors in the central nervous system has fueled investigations of insulin functions in the brain. It is also already known that insulin can influence...

Chronic neuropathic pain (CNP) is a vast world health problem often associated with the somatosensory domain. This conceptualization is problematic because, unlike most other sensations that are usually affectively neutral and may present emotional, affective, and cognitive impairments. Neuronal circuits that modulate pain can increase or decrease...

Background Alzheimer’s disease (AD) is a neurodegenerative and progressive disorder with no cure and constant failures in clinical trials. The main AD hallmarks are amyloid-β (Aβ) plaques, neurofibrillary tangles, and neurodegeneration. However, many other events have been implicated in AD pathogenesis. Epilepsy is a common comorbidity of AD and th...

About 1-2% of people worldwide suffer from epilepsy, which is characterized by unpredictable and intermittent seizure occurrence. Despite the fact that the exact origin of temporal lobe epilepsy is frequently unknown, it is frequently linked to an early triggering insult like brain damage, tumors, or Status Epilepticus (SE). We used an experimental...

Epilepsy is a neurological disease characterized by the recurrence of seizures. Seizures are associated with respiratory suppression and apneas that can increase the risk of death. The highest prevalence of seizures occurs during childhood, however, respiratory changes related to seizures during development are unknown. It is also unknown whether g...

Anxiety and pain hypersensitivity are neurobehavioral comorbidities commonly reported by patients with epilepsies, and preclinical models are suitable to investigate the neurobiology of behavioral and neuropathological alterations associated with these epilepsy-related comorbidities. This work aimed to characterize endogenous alterations in nocicep...

Background Knowledge on the neurobiological systems underlying psychiatric disorders has considerably evolved due to findings on basic research using animal models. Anxiety-like behaviors in rodents are widely explored in neuroethological apparatuses, such as the light-dark box (LDB) test through different protocols, which have been shown to influe...

Studies investigated how stressful experiences modulate physiological and behavioral responses and the consequences of stress-induced corticosterone release in anxiety-like behavior. Adolescence is crucial to brain maturation, and several neurobiological changes in this period lead individuals to increased susceptibility or resilience to aversive s...

Background Cannabidiol (CBD) has been of rapidly growing interest in the epilepsy research field due to its antiseizure properties in preclinical models and patients with pharmacoresistant epilepsy. However, little is known about CBD effects in genetic models of epilepsies. Here we assessed CBD dose–response effects in the Genetically Epilepsy Pron...

Intrahippocampal pilocarpine microinjection (H-PILO) induces status epilepticus (SE) that can lead to spontaneous recurrent seizures (SRS) and neurodegeneration in rodents. Studies using animal models have indicated that lectins mediate a variety of biological activities with neuronal benefits, especially galectin-1 (GAL-1), which has been identifi...

Wistar Audiogenic Rats (WAR) is an inbred rodent strain susceptible to acute auditory stimulation-induced seizures. However, spontaneous epileptic seizures (SES) and their associated electroencephalogram (EEG) abnormalities have not been reported in WAR kindled animals. The same is true for naïve WARs (without sound-induced seizures). An approach t...

The neurobiology and development of treatments for stress-related neuropsychiatric disorders rely heavily on animal models. However, the complexity of these disorders makes it difficult to model them entirely, so only specific features of human psychopathology are emulated and these models should be used with great caution. Importantly, the effects...

Studies have suggested an important connection between epilepsy and Alzheimer's disease (AD), mostly due to the high number of patients diagnosed with AD who develop epileptic seizures later on. However, this link is not well understood. Previous studies from our group have identified memory impairment and metabolic abnormalities in the Wistar audi...

Drug‐resistant epilepsy remains to this day as a highly prevalent condition affecting around one‐third of patients with epilepsy, despite all the research and the development of several new antiseizure medications (ASMs) over the last decades. Epilepsies are multifactorial complex diseases, commonly associated with psychiatric, neurological, and so...

Epilepsies are neurological disorders characterized by chronic seizures and their related neuropsychiatric comorbidities, such as anxiety. The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel has been implicated in the modulation of seizures and anxiety-like behaviors in preclinical models. Here, we investigated the impact of chronic e...

The incidence of chronic pain is high in the general population and it is closely related to anxiety disorders, which promote negative effects on the quality of life. The cannabinoid system has essential participation in the pain sensitivity circuit. In this perspective, cannabidiol (CBD) is considered a promising strategy for treating neuropathic...

Wistar Audiogenic Rat is an epilepsy model whose animals are predisposed to develop seizures induced by acoustic stimulation. This model was developed by selective reproduction and presents a consistent genetic profile due to the several generations of inbreeding. In this study, we performed an analysis of WAR RNA-Seq data, aiming identified at gen...

The phenomenon of plasticity in the striatum, and its relation with the striatum-nigra neuronal circuit has clinical and neurophysiological relevance to Parkinson and epilepsy. High frequency stimulation (HFS) can induce neural plasticity. Furthermore, it is possible to induce plasticity in the dorsal striatum and this can be modulated by substanti...

Cannabidiol (CBD) is a marijuana compound implicated in epilepsy treatment in animal models and pharmacoresistant patients. However, little is known about chronic CBD administration’s effects in chronic models of seizures, especially regarding its potential antiepileptogenic effects. In the present study, we combined a genetic model of epilepsy (th...

The WAG/Rij strain of rats is commonly used as a preclinical model of genetic absence epilepsy. While widely utilized, the developmental trajectory of absence seizure expression has been only partially described. Moreover, sex differences in this strain have been under-explored. Here, we longitudinally monitored male and female WAG/Rij rats to quan...

Almost 115 years ago, Alois Alzheimer described Alzheimer’s disease (AD) for the first time. Since then, many hypotheses have been proposed. However, AD remains a severe health public problem. The current medical approaches for AD are limited to symptomatic interventions and the complexity of this disease has led to a failure rate of approximately...

The Wistar audiogenic rat (WAR) strain is used as an animal model of epilepsy, which when submitted to acute acoustic stimulus presents tonic‐clonic seizures, mainly dependent on brainstem (mesencephalic) structures. However, when WARs are exposed to chronic acoustic stimuli (audiogenic kindling–AK), they usually present tonic‐clonic seizures, foll...

In this review, we will discuss in four scenarios our challenges to offer possible solutions for the puzzle associated with the epilepsies and neuropsychiatric comorbidities. We need to recognize that (1) since quite old times, human wisdom was linked to the plural (distinct global places/cultures) perception of the Universe we are in, with deep re...

Epileptogenesis is a multistage process and seizure susceptibility can be influenced by stress early in life. Wistar Audiogenic Rat (WAR) strain is an interesting model to study the association between stress and epilepsy, since it is naturally susceptible to seizures and present changes in the hypothalamus–pituitary–adrenal (HPA) axis activity. Al...

Tau is a microtubule-associated protein responsible for controlling the stabilization of microtubules in neurons. Tau function is regulated by phosphorylation. However, in some neurological diseases Tau becomes aberrantly hyperphosphorylated, which contributes to the pathogenesis of neurological diseases, known as tauopathies. Western blotting (WB)...

Cannabinoids and Cannabis-derived compounds have been receiving especial attention in the epilepsy research scenario. Pharmacological modulation of endocannabinoid system’s components, like cannabinoid type 1 receptors (CB1R) and their bindings, are associated with seizures in preclinical models. CB1R expression and functionality were altered in hu...

Epileptogenesis is a multistage process and seizure susceptibility can be influenced by stress early in life. Wistar Audiogenic Rat (WAR) strain is an interesting model to study the association between stress and epilepsy, since it is naturally susceptible to seizures and present changes in the hypothalamus-pituitary-adrenal (HPA) axis activity. Al...

Hypertension is a common comorbidity observed in individuals with epilepsy. Growing evidence suggests that lower blood pressure is associated with reduced frequency and severity of seizures. In this study, we sought to investigate whether the renin–angiotensin system (RAS), which is a critical regulator of blood pressure, is involved in the pathoge...

The endocannabinoid system (ECS) is related to several physiological processes, associated to the modulation of brain excitability, with impact in the expression of susceptibility and control of epileptic seizures. The cannabinoid receptor type 1 (CB1R) is widely expressed in the brain, especially in forebrain limbic structures. Changes in CB1R exp...

Early-life stress (ELS) is associated with a higher risk of psychopathologies in adulthood, such as depression, which may be related to persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to evaluate the effects of ELS on the functioning of the HPA axis in clinical and experimental situations. Clinically, patients...

Background: Clinical and experimental evidence indicates that olfactory stimulation modulates limbic seizures, either blocking or inducing ictal activity. Objective: We aim to evaluate the behavioral and electroencephalographic (EEGraphic) effects of dihydro-2,4,5-trimethylthiazoline (TMT) olfactory exposure on limbic seizures induced by amygdala r...

The objective of the present study was to evaluate maternal reproductive performance, body weight, and frequency of external and internal anomalies of newborns of Wistar Audiogenic Rat (WAR) females as compared with Wistar rats. The adult WAR and Wistar rats were mated within their respective strains. After confirming the pregnancy, the body weight...

Objective To evaluate the chemical and behavioral effects of 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT) after olfactory exposure and to verify their influence in the expression of acute audiogenic seizures in the Wistar Audiogenic Rat (WAR) strain. Materials and Methods: Protocol 1 TMT gas chromatography was applied to define odor saturation in a...

Wistar Audiogenic Rats (WARs) are genetically susceptible to sound-induced seizures that start in the brainstem and, in response to repetitive stimulation, spread to limbic areas, such as hippocampus. Analysis of the distribution of interevent intervals of GABAergic inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal cells showed a monoexpone...

The Wistar Audiogenic Rat (WAR) and the Genetic Audiogenic Seizure Hamster from Salamanca (GASH/Sal) strains are audiogenic epilepsy models, in which seizures are triggered by acoustic stimulation. These strains were developed by selective reproduction and have a genetic background with minimal or no variation. In the current study, we evaluated th...

Here, we investigated the participation of pro and anti-inflammatory cytokines in the spread of repeated audiogenic seizures from brainstem auditory structures to limbic areas, including the hippocampus. We used Wistar Audiogenic Rats (WARs) and Wistars submitted to the audiogenic kindling protocol with a loud broad-band noise. We measured pro and...

Epilepsy is a neurological disorder characterized by the presence of seizures and neuropsychiatric comorbidities. Despite the number of antiepileptic drugs, one-third of patients did not have their seizures under control, leading to pharmacoresistance epilepsy. Cannabis sativa has been used since ancient times in Medicine for the treatment of many...

We are pleased to present ou new research article. https://doi.org/10.1016/j.brainres.2019.146570

While acute audiogenic seizures in response to acoustic stimulus appear as an alteration in sensory-motor processing in the brainstem, the repetition of the stimulus leads to the spread of epileptic activity to limbic structures. Here, we investigated whether animals of the Wistar Audiogenic Rat (WAR) strain, genetically selected by inbreeding for...

Temporal lobe epileptic seizures are one of the most common and well-characterized types of epilepsies. The current knowledge on the pathology of temporal lobe epilepsy relies strongly on studies of epileptogenesis caused by experimentally induced status epilepticus (SE). Although several temporal lobe structures have been implicated in the epilept...

The Wistar Audiogenic Rat (WAR) strain is a genetic model of epilepsy, specifically brainstem-dependent tonic-clonic seizures, triggered by acute auditory stimulation. Chronic audiogenic seizures (audiogenic kindling) mimic temporal lobe epilepsy, with significant participation of the hippocampus, amygdala, and cortex. The objective of the present...

Previously we have demonstrated that microinjection of oxytocin (OT) into the central nucleus of amygdala (CeA) induces hypergrooming in Wistar rats, a model of compulsion. The Wistar Audiogenic Rat (WAR) strain is a genetic model of generalized tonic-clonic seizures. Here we quantified grooming behavior in WAR, with grooming scores , flowcharts an...

Temporal lobe epilepsy is often accompanied by behavioral, electroencephalographic and autonomic abnormalities. Amygdala kindling has been used as an experimental model to study epileptogenesis. Although amygdala kindling has been extensively investigated in the context of its clinical relevance to the epilepsies, potential associated respiratory a...

Stress is among the most frequently self‐reported factors provoking epileptic seizures in children and adults. It is still unclear though, why some people display stress‐sensitive seizures while others don't. Recently, we showed that young epilepsy patients with stress‐sensitive seizures exhibit a dysregulated hypothalamus‐pituitary‐adrenal (HPA)‐a...

The Wistar Audiogenic Rat (WAR) is an animal model of tonic-clonic epileptic seizures, developed after genetic selection by sister x brother inbreeding of Wistar rats susceptible to sound stimuli. Although metabolic changes have been described in this strain, nothing, however, is known about its mitochondrial metabolism. Here, we addressed mitochon...

Tau is a neuronal, microtubule-associated protein responsible for controlling the stabilization of microtubules in neurons. Tau function is regulated by phosphorylation, but in some neurological diseases it becomes aberrantly hyperphosphorylated, thus contributing to the pathogenesis of several neurological diseases such as Alzheimer's disease. Wes...

Despite the many studies focusing on epilepsy, a lot of the basic mechanisms underlying seizure susceptibility are mainly unclear. Here, we studied cellular electrical excitability, as well as excitatory and inhibitory synaptic neurotransmission of CA1 pyramidal neurons from the dorsal hippocampus of a genetic model of epilepsy, the Wistar Audiogen...

Stress is recognized as an important issue in basic and clinical neuroscience research, based upon the founding historical studies by Walter Canon and Hans Selye in the past century, when the concept of stress emerged in a biological and adaptive perspective. A lot of research after that period has expanded the knowledge in the stress field. Since...

Wistar Audiogenic Rat (WAR) strain is an animal model for epilepsy studies, the chronic multifactorial disease that affects millions of people worldwide. The animals of this strain are genetically predisposed to sound-induced seizures, called audiogenic seizures, and have been used for many years in studies to understand the mechanisms involved in...

Background: Slice cultures have been prepared from several organs. With respect to the brain, advantages of slice cultures over dissociated cell cultures include maintenance of the cytoarchitecture and neuronal connectivity. Slice cultures from adult human brain have been reported and constitute a promising method to study neurological diseases. D...

Evidences suggest the contributive role of early-life stress (ELS) to affective and anxiety disorders. Chronic exposure to the same stressor may generate habituation, while the exposure to different and repeated stressors gradually promotes maladaptive plasticity. Therefore, to further understand the effects of heterotypic stressors during early li...

O avanço da ciência, e sua relação com a formação de pessoal altamente qualificado na pós-graduação, geram pressões por desempenho e, em paralelo, dilemas éticos e conflitos de interesse entre os diversos atores envolvidos. A situação urge reflexões sobre quais são tais conflitos e como tratá-los, de forma a que sejam compatíveis com a formação de...

There are reports of patients whose epileptic seizures are prevented by means of olfactory stimulation. Similar findings were described in animal models of epilepsy, such as the electrical kindling of amygdala, where olfactory stimulation with toluene (TOL) suppressed seizures in most rats, even when the stimuli were 20% above the threshold to evok...

The Wistar Audiogenic Rat (WAR) is a well-characterized seizure-prone, inbred rodent strain that, when acutely stimulated with high-intensity sounds, develops brainstem-dependent tonic-clonic seizures that can evolve to limbic-like, myoclonic (forebrain) seizures when the acoustic stimuli are presented chronically (audiogenic kindling). In order to...

Acoustically evoked seizures (e.g., audiogenic seizures or AGS) are common in models of inherited epilepsy and occur in a variety of species including rat, mouse, and hamster. Two models that have been particularly well studied are the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR) strains. Acute and repeated AGS, as we...

Neuropathological studies often use autopsy brain tissue as controls to evaluate changes in protein or RNA levels in several diseases. In mesial temporal lobe epilepsy (MTLE), several genes are up or down regulated throughout the epileptogenic and chronic stages of the disease. Given that postmortem changes in several gene transcripts could impact...

SRS profile of the animals from the chronic group. (DOCX)

Hippocampal relative expression of Gusb, Tubb2a, B2m, Actb, and Gadph genes comparing 0h and 6h of postmortem intervals. Values are mean ± SEM, n = 6 per group. (TIF)

Objective: To test the hypothesis that naïve Wistar audiogenic rats (WAR) display ED, which is associated with increased sympathetic-mediated contractile tone and/or decreased NO-mediated relaxation responses of the cavernous tissue. Methods: Changes in the ratio of the maximal intracavernosal pressure/mean arterial pressure (ICP/MAP) after elec...

In the context of modeling epilepsy and neuropsychiatric comorbidities, we review the Wistar Audiogenic Rat (WAR), first introduced to the neuroscience international community more than 25 years ago. The WAR strain is a genetically selected reflex model susceptible to audiogenic seizures (AS), acutely mimicking brainstem-dependent tonic–clonic seiz...

Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by induc...

The involvement of miRNA in mesial temporal lobe epilepsy (MTLE) pathogenesis has increasingly become a focus of epigenetic studies. Despite advances, the number of known miRNAs with a consistent expression response during epileptogenesis is still small. Addressing this situation requires additional miRNA profiling studies coupled to detailed indiv...

Validated targets of miR-196b-5p based on miRTarBase. (XLSX)

Correlation between clinical characteristics and miR-128a-3p and miR-196b-5p expression levels in TLE patients. (DOCX)

Validated targets of miR-128a-3p based on miRTarBase. (XLSX)

Levels of miR-128a-3p and miR-196b-5p in accordance to memory performance, epilepsy remission, IPI, epileptic focus or sex. (DOCX)

Key points: It is recognized that seizures commonly cause apnoea and oxygen desaturation, but there is still a lack in the literature about the respiratory impairments observed ictally and in the post-ictal period. Respiratory disorders may involve changes in serotonergic transmission at the level of the retrotrapezoid nucleus (RTN). In this study...

Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, starting from secondary functional disorders due to several insults, including self-sustaining continuous seizures identified as status epilepticus (SE). Although hypoglycemia has been associated with SE, the effect of inhibition of the Na(+)/glucose cotransporters (SG...

Introduction: We investigated the behavioral, respiratory, and thermoregulatory responses elicited by acute exposure to both hypercapnic and hypoxic environments in Wistar audiogenic rats (WARs). The WAR strain represents a genetic animal model of epilepsy. Methods: Behavioral analyses were performed using neuroethological methods, and flowchart...

First block of raw data on thermoregulatory and ventilatory responses to both acute hypercapnia and acute hypoxia, when WAR and Wistar animals were compared. (XLS)

Second block of raw data on thermoregulatory and ventilatory responses to both acute hypercapnia and acute hypoxia, when WAR and Wistar animals were compared. (XLS)

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. There is still a debate in the literature if the respiratory arrest is the primary cause of death. Respiratory chemoreceptors neurons located in retrotrapezoid nucleus (RTN) constitute one of the main groups responsible for controlling br...

The present study aimed to investigate the behavioral and anticonvulsant effects of lamotrigine (LTG) on the genetic audiogenic seizure hamster (GASH:Sal), an animal model of audiogenic seizure that is in the validation process. To evaluate the efficiency of acute and chronic treatments with LTG, GASH:Sals were treated with LTG either acutely via i...