Amygdala inhibition impairs fear conditioning but increases the stimulus-driven activity in the inferior colliculus.

It has been shown that fear conditioning improves the steady-state evoked potentials driven by a long lasting amplitude modulated tone in the inferior colliculus. In this work we tested the hypothesis that the amygdala modulates this effect, since it plays a crucial role in assessing the biological relevance of environmental stimuli. We inhibited the basolateral nucleus of the amygdala of rats by injecting a GABAa receptor agonist (muscimol) before the recall test session of an auditory fear conditioning paradigm and recorded the evoked activity in the central nucleus of the inferior colliculus.

Auditory processing assessment suggests that Wistar audiogenic rat neural networks are prone to entrainment.

Epilepsy is a neurological disease related to the occurrence of pathological oscillatory activity, but the basic physiological mechanisms of seizure remain to be understood. Our working hypothesis is that specific sensory processing circuits may present abnormally enhanced predisposition for coordinated firing in the dysfunctional brain. Such facilitated entrainment could share a similar mechanistic process as those expediting the propagation of epileptiform activity throughout the brain.

Effects of early or late prenatal immune activation in mice on behavioral and neuroanatomical abnormalities relevant to schizophrenia in the adulthood.

Maternal immune activation (MIA) during pregnancy in rodents increases the risk of the offspring to develop schizophrenia-related behaviors, suggesting a relationship between the immune system and the brain development. Here we tested the hypothesis that MIA induced by the viral mimetic polyinosinic-polycytidylic acid (poly I:C) in early or late gestation of mice leads to behavioral and neuroanatomical disorders in the adulthood. On gestational days (GDs) 9 or 17 pregnant dams were treated with poly I:C or saline via intravenous route and the offspring behaviors were measured during adulthood.

The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation.

Many patients with epilepsy do not obtain proper control of their seizures through conventional treatment. We review aspects of the pathophysiology underlying epileptic phenomena, with a special interest in the role of the amygdala, stressing the importance of hypersynchronism in both ictogenesis and epileptogenesis. We then review experimental studies on electrical stimulation of mesiotemporal epileptogenic areas, the amygdala included, as a means to treat medically refractory epilepsy.

Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice.

Inappropriate defense-alerting reaction to fear is a common feature of neuropsychiatric diseases. Therefore, impairments in brain circuits, as well as in molecular pathways underlying the neurovegetative adjustments to fear may play an essential role on developing neuropsychiatric disorders. Here we tested the hypothesis that interfering with angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis homeostasis, which appears to be essential to arterial pressure control, would affect fear memory and extinction.

Protein-caloric dietary restriction inhibits mossy fiber sprouting in the pilocarpine model of TLE without significantly altering seizure phenotype.

Given the known effects of undernutrition over protein synthesis, we promoted neonatal undernutrition to evaluate its effect over the neuroplasticity induced by the pilocarpine model of epilepsy and also over spontaneous seizure expression. A well-nourished group (WN), fed ad libitum rat chow diet, and an undernourished group (UN), fed 60% of the amount of diet consumed by a WN group, were submitted to status epilepticus (SE) through pilocarpine injection at 45 days of age. Thereafter, animals were behaviorally monitored for 6h daily to quantify seizures.

The 5-lipoxygenase (5-LOX) Inhibitor Zileuton Reduces Inflammation and Infarct Size with Improvement in Neurological Outcome Following Cerebral Ischemia.

Stroke is one of the most frequent causes of death and disability worldwide causing a major clinical and socioeconomic impact. Although the pathophysiology of brain ischemia and reperfusion is complex, the inflammatory process plays an important role in pathogenesis, contributing to the expansion of brain injury. The 5-lipoxygenase (5-LOX) is a key enzyme in the biosynthesis of the leukotrienes and has been implicated and in the central nervous system (CNS) disorders such as Alzheimer's disease and acute ischemic stroke.

Wistar Audiogenic Rats (WAR) exhibit altered levels of cytokines and brain-derived neurotrophic factor following audiogenic seizures.

Increasing body of evidence suggests that inflammatory and neurotrophic factors might be important for epileptogenesis. Most animal studies demonstrated altered levels of these mediators in drug-induced models of seizures and epilepsy. In the present study, we investigated the production of cytokines and a neurotrophin in the brain of Wistar Audiogenic Rats (WAR), a genetic model of epilepsy, stimulated with high-intensity sound.

Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity.

Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli.

Object recognition memory deficit and depressive-like behavior caused by chronic ovariectomy can be transitorialy recovered by the acute activation of hippocampal estrogen receptors.

It is well known that estradiol (E2) replacement therapy is effective on restoring memory deficits and mood disorders that may occur during natural menopause or after surgical ovarian removal (ovariectomy, OVX). However, it is still unknown the effectiveness of acute and localized E2 administration on the effects of chronic OVX. Here we tested the hypothesis that the intra-hippocampal E2 infusion, as well as specific agonists of estrogen receptors (ERs) alpha (ERα) and beta (ERβ), are able to mend novel object recognition (NOR) memory deficit and depressive-like behavior caused by 12 weeks of OVX.

PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine.

Phosphatidylinositol 3-kinase (PI3K) is an enzyme involved in different pathophysiological processes, including neurological disorders. However, its role in seizures and postictal outcomes is still not fully understood. We investigated the role of PI3Kγ on seizures, production of neurotrophic and inflammatory mediators, expression of a marker for microglia, neuronal death and hippocampal neurogenesis in mice (WT and PI3Kγ(-/-)) subjected to intrahippocampal microinjection of pilocarpine.

The role of dorsomedial hypotalamus ionotropic glutamate receptors in the hypertensive and tachycardic responses evoked by Tityustoxin intracerebroventricular injection.

The scorpion envenoming syndrome is an important worldwide public health problem due to its high incidence and potential severity of symptoms. Some studies address the high sensitivity of the central nervous system to this toxin action. It is known that cardiorespiratory manifestations involve the activation of the autonomic nervous system.

Effects of tityustoxin on cerebral inflammatory response in young rats.

Accidents caused by scorpion stings, mainly affecting children, are considered an important cause of morbidity and mortality in tropical countries. Clinical studies demonstrate the relevant role of systemic inflammatory events in scorpion envenoming. However, remains poorly understood whether the major lethal component in Tityus serrulatus venom, tityustoxin (TsTX), is able to induce inflammatory responses in the cerebral microcirculation.

Temporally unstructured electrical stimulation to the amygdala suppresses behavioral chronic seizures of the pilocarpine animal model.

Electrical stimulation applied to the basolateral amygdala in the pentylenetetrazole animal model of seizures may result in either a proconvulsant or an anticonvulsant effect depending on the interpulse intervals used: periodic or nonperiodic, respectively. We tested the effect of this electrical stimulation temporal coding on the spontaneous and recurrent behavioral seizures produced in the chronic phase of the pilocarpine animal model of temporal lobe epilepsy, an experimental protocol that better mimics the human condition. After 45 days of the pilocarpine-induced status epilepticus, male Wistar rats were submitted to a surgical procedure for the implantation of a bipolar electrical stimulation electrode in the right basolateral amygdala and were allowed to recover for seven days.

Murine model to study brain, behavior and immunity during hepatic encephalopathy.

Aim: To propose an alternative model of hepatic encephalopathy (HE) in mice, resembling the human features of the disease.

Methods: Mice received two consecutive intraperitoneal injections of thioacetamide (TAA) at low dosage (300 mg/kg). Liver injury was assessed by serum transaminase levels (ALT) and liver histology (hematoxylin and eosin).

Anticonvulsant effects of N-arachidonoyl-serotonin, a dual fatty acid amide hydrolase enzyme and transient receptor potential vanilloid type-1 (TRPV1) channel blocker, on experimental seizures: the roles of cannabinoid CB1 receptors and TRPV1 channels.

Selective blockade of anandamide hydrolysis, through the inhibition of the FAAH enzyme, has anticonvulsant effects, which are mediated by CB1 receptors. Anandamide, however, also activates TRPV1 channels, generally with an opposite outcome on neuronal modulation. Thus, we suggested that the dual FAAH and TRPV1 blockade with N-arachidonoyl-serotonin (AA-5-HT) would be efficacious in inhibiting pentylenetetrazole (PTZ)-induced seizures in mice.

Focus on desynchronization rather than excitability: a new strategy for intraencephalic electrical stimulation.

Epilepsy is a severely debilitating brain disease, often associated with premature death, which has an urgent need for alternative methods of treatment. In fact, roughly 25% of patients with epilepsy do not have seizures satisfactorily controlled by pharmacological treatment, and 30% of these patients with treatment-refractory seizures are not even eligible for ablative surgery. Epilepsy is most readily identifiable by its seizures and/or paroxysmal events, mostly viewed as spontaneously recurrent and unpredictable, which are caused by stereotyped changes in neurological function associated with hyperexcitability and hypersynchronicity of the underlying neural networks.

Temporal rearrangement of pre-ictal PTZ induced spike discharges by low frequency electrical stimulation to the amygdaloid complex.

Background: Epilepsy is a common neurological disease affecting over 40 million people worldwide. The foremost important challenge of epileptologists has been to control and predict the recurrent and spontaneous seizures of epileptic patients. The application of low frequency electrical stimulation (LFS) in deep brain structures has shown promising results in seizure control.

Enriched environment increases neurogenesis and improves social memory persistence in socially isolated adult mice.

Social memory consists of the information necessary to identify and recognize cospecifics and is essential to many forms of social interaction. Social memory persistence is strongly modulated by the animal's experiences. We have shown in previous studies that social isolation (SI) in adulthood impairs social memory persistence and that an enriched environment (EE) prevents this impairment.

Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation.

Severe scorpion envenoming (SSE) is more frequent in children and is characterized by systemic dysfunctions with a mortality rate of up to 9%. Recent evidence shows that the central nervous system (CNS) plays a key role in triggering the cascade of symptoms present in SSE. The age-dependent role of the CNS in SSE lethality may be summarized in 3 hypotheses: (1) the shown increased blood brain barrier permeability of infants to the toxins would especially and primarily compromise neurovegetative control areas, (2) the neurons within these areas have high affinity to the toxins, and (3) the neurovascular interaction is such that SSE metabolically compromises proper function of toxin-targeted areas.

Malnutrition alters the cardiovascular responses induced by central injection of tityustoxin in Fischer rats.

Scorpion envenoming and malnutrition are considered two important public health problems in Brazil, involving mainly children. Both these conditions are more common among the economically stratified lower income portion of the population, thus suggesting that these factors should be analyzed concomitantly. It is known that cardiorespiratory manifestations, as cardiac arrhythmias, arterial hypertension and hypotension, pulmonary edema and circulatory failure are the main "causa mortis" of scorpion envenomation.

A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4.

Many studies have shown that minocycline, an antibacterial tetracycline, suppresses experimental pain. While minocycline's positive effects on pain resolution suggest that clinical use of such drugs may prove beneficial, minocycline's antibiotic actions and divalent cation (Ca(2+); Mg(2+)) chelating effects detract from its potential utility. Thus, we tested the antiallodynic effect induced by a non-antibacterial, non-chelating minocycline derivative in a model of neuropathic pain and performed an initial investigation of its anti-inflammatory effects in vitro.

Effects of cannabinoids and endocannabinoid hydrolysis inhibition on pentylenetetrazole-induced seizure and electroencephalographic activity in rats.

Cannabinoids and drugs that increase endocannabinoid levels inhibit neuronal excitability and restrain epileptic seizures through CB1 receptor activation. Nevertheless, the results have not been entirely consistent, since pro-convulsant effects have also been reported. The present study aimed to further investigate the effects of cannabinoid-related compounds on seizures induced by pentylenetetrazole (PTZ) in rats.

Object recognition memory and temporal lobe activation after delayed estrogen replacement therapy.

The critical window hypothesis predicts that estrogen replacement therapy (ERT) must be administered early on the menopause or ovariectomy (OVX) to positively affect cognition. However, the neural substrates, underling the time dependent efficacy of ERT, are still not completely known. In order to address this issue, we submitted female mice to 12 weeks of OVX followed by 5 weeks of chronic ERT (OVX(E2)).

Swim training attenuates oxidative damage and promotes neuroprotection in cerebral cortical slices submitted to oxygen glucose deprivation.

Although it is well known that regular exercise may promote neuroprotection, the mechanisms underlying this effect are still not fully understood. We investigated if swim training promotes neuroprotection by potentiating antioxidant pathways, thereby decreasing the effects of oxidative stress on glutamate and nitric oxide release. Male Wistar rats (n=36) were evenly randomized into a trained group (TRA) (5 days/week, 8 weeks, 30 min) and a sedentary group (SED).