Flavio Del Vecchio

Behavioral, Morphologic, and Electroencephalographic Evaluation of Seizures Induced by Intrahippocampal Microinjection of Pilocarpine

Summary:  Purpose: We studied, by means of video‐EEG and neo‐Timm histochemistry, the behavioral, electrophysiologic, and structural characteristics of seizures induced by intrahippocampal microinjection of pilocarpine (HIP‐PILO), a selective model of temporal lobe epilepsy (TLE).

Convulsant activity and neurochemical alterations induced by a fraction obtained from fruit Averrhoa carambola (Oxalidaceae: Geraniales).

We obtained a neurotoxic fraction (AcTx) from star fruit (Averrhoa carambola) and studied its effects on GABAergic and glutamatergic transmission systems. AcTx had no effect on GABA/glutamate uptake or release, or on glutamate binding. However, it specifically inhibited GABA binding in a concentration-dependent manner (IC(50)=0.89muM). Video-electroencephalogram recordings demonstrated that following cortical administration of AcTx, animals showed behavioral changes, including tonic-clonic seizures, evolving into status epilepticus, accompanied by cortical epileptiform activity. Chemical characterization of AcTx showed that this compound is a nonproteic molecule with a molecular weight less than 500, differing from oxalic acid. This neurotoxic fraction of star fruit may be considered a new tool for neurochemical and neuroethological research.

Elucidating the Neurotoxicity of the Star Fruit

Caramboxin: Patients suffering from chronic kidney disease are frequently intoxicated after ingesting star fruit. The main symptoms of this intoxication are named in the picture. Bioguided chemical procedures resulted in the discovery of caramboxin, which is a phenylalanine-like molecule that is responsible for intoxication. Functional experiments in vivo and in vitro point towards the glutamatergic ionotropic molecular actions of caramboxin, which explains its convulsant and neurodegenerative properties.

Correlation between shaking behaviors and seizure severity in five animal models of convulsive seizures

Wet dog shakes (WDS) and head shakes (HS) are associated with experimentally induced convulsive seizures. We sought to determine whether these behaviors are correlated or not with major (status epilepticus (SE) or fully kindled animals) or minor (non-SE or partially kindled animals) seizure severity. WDS are directly correlated with SE induced by intracerebral star fruit extract (Averrhoa carambola) injection and with kindled animals in the amygdala fast kindling model. On the other hand, WDS are inversely correlated with SE induced by intracerebral bicuculline and pilocarpine injections. Systemic pilocarpine in animals pretreated with methyl-scopolamine barely induced WDS or HS. The role of shaking behaviors may vary from ictal to anticonvulsant depending on the experimental seizure model, circuitries involved, and stimulus intensity. The physical presence of acrylic helmets may per se inhibit the HS response. Also, methyl-scopolamine, a drug incapable of crossing the blood-brain barrier, can induce HS in animals without acrylic helmets.

Antinociceptive Effect of Stimulating the Occipital or Retrosplenial Cortex in Rats

UNLABELLED A role for the occipital or retrosplenial cortex in nociceptive processing has not been demonstrated yet, but connections from these cortices to brain structures involved in descending pain-inhibitory mechanisms were already demonstrated. This study demonstrated that the electrical stimulation of the occipital or retrosplenial cortex produces antinociception in the rat tail-flick and formalin tests. Bilateral lesions of the dorsolateral funiculus abolished the effect of cortical stimulation in the tail-flick test. Injection of glutamate into the same targets was also antinociceptive in the tail-flick test. No rats stimulated in the occipital or retrosplenial cortex showed any change in motor performance on the Rota-rod test, or had epileptiform changes in the EEG recording during or up to 3 hours after stimulation. The antinociception induced by occipital cortex stimulation persisted after neural block of the retrosplenial cortex. The effect of retrosplenial cortex stimulation also persisted after neural block of the occipital cortex. We conclude that stimulation of the occipital or retrosplenial cortex in rats leads to antinociception activating distinct descending pain-inhibitory mechanisms, and this is unlikely to result from a reduced motor performance or a postictal phenomenon. PERSPECTIVE This study presents evidence that stimulation of the retrosplenial or occipital cortex produces antinociception in rat models of acute pain. These findings enhance our understanding of the role of the cerebral cortex in control of pain.

Different types of status epilepticus lead to different levels of brain damage in rats

We investigated a possible correlation between behavior during status epilepticus (SE) and underlying brain damage. Adult rats were electrically stimulated in the left amygdala to induce SE, which was stopped 2 hours later. We observed two different types of SE: (1) typical SE (TSE), with facial automatisms, neck and forelimb myoclonus, rearing and falling, and tonic-clonic seizures; (2) ambulatory SE (ASE), with facial automatisms, neck myoclonus, and concomitant ambulatory behavior. TSE was behaviorally more severe than ASE (P<0.05). Histology revealed neuronal loss in several brain areas. There was a positive correlation between SE type and amount of injured areas 24 hours and 14 days after SE (P<0.01). The areas more affected were piriform cortex and hippocampal formation. We suggest quality of seizures during SE may be considered in further SE studies, as our results indicate its influence on the severity of brain damage following this paradigm.

Cortical stimulation in conscious rats controls joint inflammation

ABSTRACT The neuronal control of the immune system is fundamental to the development of new therapeutic strategies for inflammatory disorders. Recent studies reported that afferent vagal stimulation attenuates peripheral inflammation by activating specific sympathetic central and peripheral networks, but only few subcortical brain areas were investigated. In the present study, we report that afferent vagal stimulation also activates specific cortical areas, as the parietal and cingulate cortex. Since these cortical structures innervate sympathetic‐related areas, we investigate whether electrical stimulation of parietal cortex can attenuate knee joint inflammation in non‐anesthetized rats. Our results show that cortical stimulation in rats increased sympathetic activity and improved joint inflammatory parameters, such as local neutrophil infiltration and pro‐inflammatory cytokine levels, without causing behavioral disturbance, brain epileptiform activity or neural damage. In addition, we superposed the areas activated by afferent vagal or cortical stimulation to map common central structures to depict a brain immunological homunculus that can allow novel therapeutic approaches against inflammatory joint diseases, such as rheumatoid arthritis. HIGHLIGHTSAfferent vagus nerve stimulation activates subcortical and cortical brain areas.Cortical electrical stimulation (CES) activates similar subcortical and cortical brain areas.CES and Aff VNS reduced joint inflammation.CES does not cause behavioral disturbance, epileptiform activity or neural damage.

Intense olfactory stimulation blocks seizures in an experimental model of epilepsy

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 evoke seizures in already kindled animals. The Wistar Audiogenic Rat (WAR) strain is a model of tonic-clonic seizures induced by acute acoustic stimulation, although it also expresses limbic seizures when repeated acoustic stimulation occurs - a process known as audiogenic kindling (AK). The aim of this study was to evaluate whether or not the olfactory stimulation with TOL would interfere on the behavioral expression of brainstem (acute) and limbic (chronic) seizures in the WAR strain. For this, animals were exposed to TOL or saline (SAL) and subsequently exposed to acoustic stimulation in two conditions that generated: I) acute audiogenic seizures (only one acoustic stimulus, without previous seizure experience before of the odor test) and II) after AK (20 acoustic stimuli [2 daily] before of the protocol test). We observed a decrease in the seizure severity index of animals exposed only to TOL in both conditions, with TOL presented 20s before the acoustic stimulation in both protocols. These findings were confirmed by behavioral sequential analysis (neuroethology), which clearly indicated an exacerbation of clusters of specific behaviors such as exploration and grooming (self-cleaning), as well as significant decrease in the expression of brainstem and limbic seizures in response to TOL. Thus, these data demonstrate that TOL, a strong olfactory stimulus, has anticonvulsant properties, detected by the decrease of acute and AK seizures in WARs.