Otoni Cardoso do Vale

Oxidative stress and epilepsy: literature review.

Backgrounds. The production of free radicals has a role in the regulation of biological function, cellular damage, and the pathogenesis of central nervous system conditions. Epilepsy is a highly prevalent serious brain disorder, and oxidative stress is regarded as a possible mechanism involved in epileptogenesis. Experimental studies suggest that oxidative stress is a contributing factor to the onset and evolution of epilepsy. Objective. A review was conducted to investigate the link between oxidative stress and seizures, and oxidative stress and age as risk factors for epilepsy. The role of oxidative stress in seizure induction and propagation is also discussed. Results/Conclusions. Oxidative stress and mitochondrial dysfunction are involved in neuronal death and seizures. There is evidence that suggests that antioxidant therapy may reduce lesions induced by oxidative free radicals in some animal seizure models. Studies have demonstrated that mitochondrial dysfunction is associated with chronic oxidative stress and may have an essential role in the epileptogenesis process; however, few studies have shown an established link between oxidative stress, seizures, and age.

Anticonvulsant effects of agomelatine in mice

Agomelatine is a potent MT1 and MT2 melatonin receptor agonist and a 5-HT2C serotonin receptor antagonist. We analyzed whether agomelatine has anticonvulsant properties. The anticonvulsant activity of agomelatine (25, 50 or 75 mg/kg, i.p.) was evaluated in mouse models of pentylenetetrazole (PTZ-85 mg/kg, i.p.), pilocarpine (400mg/kg, i.p.), picrotoxin (7 mg/kg, i.p.), strychnine (75 mg/kg, i.p.) or electroshock-induced convulsions. In the PTZ-induced seizure model, agomelatine (at 25 or 50mg/kg) showed a significant increase in latency to convulsion, and agomelatine (at 50 or 75 mg/kg) also increased significantly time until death. In the pilocarpine-induced seizure model, only agomelatine in high doses (75 mg/kg) showed a significant increase in latency to convulsions and in time until death. In the strychnine-, electroshock- and picrotoxin-induced seizure models, agomelatine caused no significant alterations in latency to convulsions and in time until death when compared to controls. Our results suggest that agomelatine has anticonvulsant activity shown in PTZ- or pilocarpine-induced seizure models.

Small fiber dysfunction in patients with Wilson's disease

OBJECTIVE Patients with Wilsons disease (WD) may develop a wide variety of neuropsychiatric symptoms, but there are few reports of autonomic dysfunction. Here, we described evidence of small fiber and/or autonomic dysfunction in 4 patients with WD and levodopa-responsive parkinsonism. METHOD We reviewed the charts of 4 patients with WD who underwent evaluation for the presence of neuromuscular dysfunction and water-induced skin wrinkling test (SWT). RESULTS Two men and 2 women (33±3.5 years) with WD were evaluated. They all had parkinsonism at some point during their disease course. Parkinsonism on patient 4 almost completely subsided with treatment of WD. Two patients had significant sensory and 2 significant autonomic complaints, including syncopal spells. NCS/EMG was normal in all but SWT was abnormal in half of them (mean 4-digit wrinkling of 0.25 and 1). DISCUSSION A subset of patients with WD exhibit evidence of abnormal skin wrinkling test (small fiber neuropathy).

Motor neuron diseases in the University Hospital of Fortaleza (Northeastern Brazil): a clinico-demographic analysis of 87 cases

In this retrospective (1980-1998) study, we have analyzed clinico-demographically, from the records of the University Hospital of Fortaleza (Brazil), a group of 87 patients showing signs and symptoms of motor neuron diseases (MNDs). Their diagnosis was determined clinically and laboratorially. The WFN criteria were used for amyotrophic lateral sclerosis (ALS) diagnosis. The clinico-demographic analysis of the 87 cases of MNDs showed that 4 were diagnosed as spinal muscular atrophy (SMA), 5 cases as ALS subsets: 2 as progressive bulbar paralysis (PBP), 2 as progressive muscular atrophy (PMA) and 1 as monomelic amyotrophy (MA), and 78 cases of ALS. The latter comprised 51 males and 27 females, with a mean age of 42.02 years. They were sub-divided into 4 groups according to age: from 15 to 29 years (n= 17), 30 to 39 years (n= 18), 40 to 69 years (n= 39) and 70 to 78 years (n= 4). From the 78 ALS patients, 76 were of the classic sporadic form whilst only 2 were of the familial form. The analysis of the 87 patients with MNDs from the University Hospital of Fortaleza showed a predominance of ALS patients, with a high number of cases of juvenile and early onset adult sporadic ALS.

A dual action of alpha-lipoic acid in the brain: an electrophysiological evaluation

Oxidative stress causes metabolic and structural abnormalities during reperfusion. In an animal model of electrophysiological evaluation of cerebral ischemia-reperfusion, alpha-lipoic acid effect on the oxidative stress was studied by mean absolute amplitude of EEG spectra evaluation. The left carotideal infusion of 3.03 mM alpha-lipoic acid in Wistar rats after cerebral ischemia and reperfusion caused initial reduction and partial final recuperation of the various EEG spectral frequency mean absolute amplitudes (p<0.05). The left intracarotideal infusion of 6.06 mM alpha-lipoic acid significantly reverted the induced depression of mean absolute amplitude of theta and delta spectra. Nevertheless there was an increasing pattern of ischemia demonstrated by mean absolute amplitude depression of almost all EEG spectra with 60.6 mM alpha-lipoic acid infusion. These observations suggest that, depending on the administered concentration, alpha-lipoic acid may act in a dual way, protecting from ischemia at lower concentrations and worsening this process at higher doses.

Essential oil of Croton zehntneri and its main constituent anethole block excitability of rat peripheral nerve.

Croton zehntneri is an aromatic plant native to Northeast Brazil and employed by local people to treat various diseases. The leaves of this plant have a rich content of essential oil. The essential oil of C. zehntneri samples, with anethole as the major constituent and anethole itself, have been reported to have several pharmacological activities such as antispasmodic, cardiovascular, and gastroprotective effects and inducing the blockade of neuromuscular transmission and antinociception. Since several works have demonstrated that essential oils and their constituents block cell excitability and in view of the multiple effects of C. zehntneri essential oil and anethole on biological tissues, we undertook this investigation aiming to characterize and compare the effects of this essential oil and its major constituent on nerve excitability. Sciatic nerves of Wistar rats were used. They were mounted in a moist chamber, and evoked compound action potentials were recorded. Nerves were exposed in vitro to the essential oil of C. zehntneri and anethole (0.1-1 mg/mL) up to 180 min, and alterations in excitability (rheobase and chronaxie) and conductibility (peak-to-peak amplitude and conduction velocity) parameters of the compound action potentials were evaluated. The essential oil of C. zehntneri and anethole blocked, in a concentration-dependent manner with similar pharmacological potencies (IC50: 0.32 ± 0.07 and 0.22 ± 0.11 mg/mL, respectively), rat sciatic nerve compound action potentials. Strength-duration curves for both agents were shifted upward and to the right compared to the control curve, and the rheobase and chronaxie were increased following essential oil and anethole exposure. The time courses of the essential oil of C. zehntneri and anethole effects on peak-to-peak amplitude of compound action potentials followed an exponential decay and reached a steady state. The essential oil of C. zehntneri and anethole caused a similar reduction in conduction velocities of the compound action potential waves investigated. In conclusion, we demonstrated here that the essential oil of C. zehntneri blocks neuronal excitability and that this effect, which can be predominantly attributable to its major constituent, anethole, is important since these agents have several pharmacological effects likely related to the alteration of excitability. This finding is relevant due to the use of essential oils in aromatherapy and the low acute toxicity of this agent, which exhibits other effects of potential therapeutic usefulness.

Epilepsia partialis continua (Koshevnikov): a preliminary case report

We report on the preliminary clinical and electrophysiological aspects of an in-patient possibly presenting epilepsia partialis continua (Koshevnikov). We discuss the different etiologies and emphasize on the possible idiopathic form in this case.

n5-STZ Diabetic Model Develops Alterations in Sciatic Nerve and Dorsal Root Ganglia Neurons of Wistar Rats

One experimental model of diabetes mellitus (DM) similar to type II DM, called n5-STZ, is obtained by a single injection (via i.p.) of streptozotocin (STZ) in the 5th day of life of newborn rats. The present investigation aimed to characterize alterations in excitability of rat peripheral neurons in n5-STZ model. n5-STZ DM was induced, and electrophysiological evaluation was done at 12th week of rat life. Rats developed glucose intolerance, sensory alteration, and hyperglycemia or near-normoglycemia (21.2 ± 1.6 and 7.4 ± 0.4 mmol/L). In near-normoglycemia group the significant electrophysiological alteration observed was decreased in amplitude of 2nd wave (2nd component, conduction velocity: 48.8 m/s) of compound action potential (CAP) of sciatic nerve. For hyperglycemic rats, decreased excitability, amplitude, and conduction velocity of 2nd CAP component of sciatic nerve were found; a depolarization of resting potential (4-5 mV) and reduction in maximum ascendant and descendant inclinations of action potential were found in DRG neurons but no alteration on Na+ current (INa+). Thus, n5-STZ rats develop alterations in excitability which were related to glycemic levels but were not likely attributable to changes on INa+. Our data confirm that n5-STZ model is a useful model to study type II DM.

Average spectral power changes at the hippocampal electroencephalogram in schizophrenia model induced by ketamine

The use of ketamine (Ket) as a pharmacological model of schizophrenia is an important tool for understanding the main mechanisms of glutamatergic regulated neural oscillations. Thus, the aim of the current study was to evaluate Ket‐induced changes in the average spectral power using the hippocampal quantitative electroencephalography (QEEG). To this end, male Wistar rats were submitted to a stereotactic surgery for the implantation of an electrode in the right hippocampus. After three days, the animals were divided into four groups that were treated for 10 consecutive days with Ket (10, 50, or 100 mg/kg). Brainwaves were captured on the 1st or 10th day, respectively, to acute or repeated treatments. The administration of Ket (10, 50, or 100 mg/kg), compared with controls, induced changes in the hippocampal average spectral power of delta, theta, alpha, gamma low or high waves, after acute or repeated treatments. Therefore, based on the alterations in the average spectral power of hippocampal waves induced by Ket, our findings might provide a basis for the use of hippocampal QEEG in animal models of schizophrenia.

A propósito de um caso de pupila tônica bilateral (síndrome de Holmes-Adie)

The authors present a case of bilateral tonic pupil and discuss clinical and physiopathological aspects of this syndrome. They discuss some elements necessary for the understanding of the etiopathogenesis of the disease.