Carla A. Scorza

Differential effects of spontaneous versus forced exercise in rats on the staining of parvalbumin-positive neurons in the hippocampal formation

To investigate whether the type of physical activity, voluntary or forced, would promote different morphological changes in hippocampal formation we performed an immunocytochemical study using the parvalbumin (PV) distribution as a marker. Animals submitted to the voluntary exercise were placed in a voluntary wheel running and those submitted to the forced exercise were placed in a motor driven treadmill. Both exercise groups were submitted to 10 consecutive days of physical activity. It was observed a higher number of PV-positive cells in the hilus of dentate gyrus (DG) in the voluntary and forced exercise groups when compared to the control group. The voluntary exercise group also presented a stronger fiber staining in the DG hilus than the forced exercise and control groups. In contrast, no differences were found in the pattern of PV staining in CA1/CA3 region between exercise and control groups. These findings demonstrate that physical activity leads to prominent plastic changes in the hippocampal formation of rats that were more evident following voluntary activity.

Neuroprotective activity of omega-3 fatty acids against epilepsy-induced hippocampal damage: Quantification with immunohistochemical for calcium–binding proteins

To investigate whether n-3 polyunsaturated fatty acids (n-3 PUFAs) would promote different morphological changes in the hippocampal formation of rats with epilepsy, we performed an immunocytochemical study using parvalbumin (PV) and calretinin (CR) distribution as a marker. Animals subjected to the experimental model of epilepsy with a single dose of pilocarpine were randomly divided into the following groups: animals with epilepsy treated daily with vehicle (EV) and animals with epilepsy treated daily with 85 mg/kg n-3 PUFAs (EW). Control animals administered saline were also randomly divided into two other groups: animals treated daily with vehicle (CV) and animals treated daily with 85 mg/kg n-3 PUFAs (CW). A larger number of PV-positive neurons were observed in EW when compared with EV, CV, and CW. Similarly, there were significantly more CR-positive neurons in EW than in EV. These findings demonstrate that omega-3 fatty acids prevent status epilepticus-associated neuropathological changes in the hippocampal formation of rats with epilepsy.

Is physical activity beneficial for recovery in temporal lobe epilepsy? Evidences from animal studies.

Exposure to different physical and cognitive stimulus have been shown to induce extensive neuronal plasticity in both undamaged and injured central nervous system, such as enhanced neurogenesis in the dentate gyrus of the hippocampus, up-regulation of neurotrophic factors and improved learning and memory. Neuronal plasticity also is found during certain neurodegenerative conditions, including the temporal lobe epilepsy (TLE). TLE is the most common form of partial epilepsy, characterized by atrophy of mesial temporal structures, mossy fiber sprouting, spontaneous recurrent seizures and cognitive deficits. In view of the fact that physical activity has been found to be beneficial for treating animal models of Parkinsons, Alzheimers and Huntingtons diseases, there is considerable interest in determining the efficacy of this strategy for preventing or treating chronic TLE. This review discusses the positive effects of program of physical exercise in experimental models of epilepsy. Thus, considerations of the potential application of physical exercise strategy for preventing or treating TLE are highlighted.

Acute and chronic exercise modulates the expression of MOR opioid receptors in the hippocampal formation of rats.

Exercise stimulates the release of beta-endorphin and other endogenous opioid peptides that are believed to be responsible for changes in mood, perception of pain and also performance. Although the vast majority of literature data support the role of physical exercise in increasing beta-endorphin levels, indirect measures such as increased endorphin levels in peripheral blood do not reflect opioid levels in the central nervous system. The purpose of the present study was to verify whether acute and chronic exercise using both voluntary and forced exercise procedures could modify the expression of μ-opioid receptors (MOR) in rat hippocampal formation. Immunoblotting analysis showed significantly enhanced MOR expression in the hippocampal formation in the acute (forced and voluntary) exercise groups when compared to the control group. Conversely, a significant reduction of MOR expression was noted in the chronic forced and chronic voluntary exercise groups compared to the acute forced and voluntary groups respectively. MOR expression was not significantly different in rats trained using both acute or chronic exercise. Immunohistochemistry analysis showed a higher number of MOR-positive cells for acute forced and voluntary exercise groups in the CA1, CA3, hilus and dentate gyrus regions compared to the control group. Our findings indicate that acute and chronic exercise modulates MOR expression in the hippocampal formation of rats.

Lovastatin reduces neuronal cell death in hippocampal CA1 subfield after pilocarpine-induced status epilepticus: preliminary results

OBJECTIVE To further characterize the capacity of lovastatin to prevent hippocampal neuronal loss after pilocarpine-induced status epilepticus (SE) METHOD: Adult male Wistar rats were divided into four groups: (A) control rats, received neither pilocarpine nor lovastatin (n=5); (B) control rats, received just lovastatin (n=5); (C) rats that received just pilocarpine (n=5); (D) rats that received pilocarpine and lovastatin (n=5). After pilocarpine injection (350 mg/kg, i.p.), only rats that displayed continuous, convulsive seizure activity were included in our study. Seizure activity was monitored behaviorally and terminated with an injection of diazepam (10 mg/kg, i.p.) after 4 h of convulsive SE. The rats treated with lovastatin received two doses of 20 mg/kg via an oesophagic probe immediately and 24 hours after SE induction. Seven days after pilocarpine-induced SE, all the animals were perfused and their brains were processed for histological analysis through Nissl method. RESULTS The cell counts in the Nissl-stained sections performed within the hippocampal formation showed a significant cell loss in rats that received pilocarpine and presented SE (CA1=26.8 +/- 13.67; CA3=38.1 +/- 7.2; hilus=43.8 +/- 3.95) when compared with control group animals (Group A: CA1=53.2 +/- 9.63; CA3=63.5 +/- 13.35; hilus=59.08 +/- 10.24; Group B: CA1=74.3 +/- 8.16; CA3=70.1 +/- 3.83; hilus=70.6 +/- 5.10). The average neuronal cell number of CA1 subfield of rats that present SE and received lovastatin (44.4 +/- 17.88) was statically significant increased when compared with animals that just presented SE. CONCLUSION Lovastatin exert a neuroprotective role in the attenuation of brain damage after SE.

Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome

OBJECTIVE To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. METHOD Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patients clinical data and surgical outcome were reviewed. RESULTS Occurrence of initial precipitating insult (IPI), as well as better postoperative seizure control (i.e. Engel class 1), were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively). CONCLUSION Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS.

Physical exercise in epilepsy: What kind of stressor is it?

Stress has been considered the most frequently self-reported precipitant of seizures in people with epilepsy. The literature documents that physical stress, that is, physical exercise, can have beneficial effects in people with epilepsy. In view of evidence indicating that sensitivity to stress is reduced after a physical exercise program, physical activity could be a potential candidate for stress reduction in people with epilepsy. This review considers how physical exercise could contribute to reduce seizure susceptibility and, hence, seizure frequency. Possible mechanisms by which exercise can be beneficial for people with epilepsy are highlighted. Hypothalamic-pituitary-adrenal axis adaptation, neurotransmitter system modulation, and metabolic and neuroendocrine changes may interfere with seizure susceptibility. The psychological stress of different sports activities is an important concern that must also be taken into account. Overall, among stress reduction therapies for the treatment of seizures, exercise might be a potential candidate.

Estudo qualitativo da formação hipocampal de animais hipertensos com epilepsia

RESUMO - O objetivo deste estudo foi avaliar qualitativamente o hipocampo e o giro dentado de ratos es-pontaneamente hipertensos (SHR) com epilepsia. Metodo: Os animais foram divididos em 4 grupos: Wistarcontrole, Wistar com epilepsia, SHR controle e SHR com epilepsia. Para inducao da epilepsia, utilizamos omodelo da pilocarpina. Apos os animais apresentarem crises espontâneas e recorrentes, o tecido cerebraldos animais foi encaminhado para analise histologica atraves dos metodos de Nissl e neo-Timm. Resultados:Nos animais Wistar e SHR controle submetidos a coloracao de Nissl observamos a manutencao das camadascelulares da formacao hipocampal. Nos animais Wistar com epilepsia verificamos intensa morte neuronalna regiao CA1 e CA3 do hipocampo e no hilo do giro dentado. Nos animais SHR com epilepsia verificou-se a presenca de atrofia hipocampal com dilatacao do sistema ventricular. A coloracao de neo-Timm reve-lou a presenca de brotamento supragranular em todos os animais com epilepsia. Conclusao: Foram encon-tradas alteracoes neuropatologicas na citoarquitetura hipocampal nos animais Wistar com epilepsia e SHRcom epilepsia, demonstrando que a epilepsia isoladamente ou associadamente a hipertensao sao capazesde causar destruicao neuronal. PALAVRAS-CHAVE: epilepsia, hipertensao arterial, crise epileptica, pilocarpina.Qualitative study of hippocampal formation in hypertensive rats with epilepsy.ABSTRACT - The aim of our study was to investigate the hippocampus and dentate gyrus neuropathologicalfeatures of spontaneous hypertensive rats (SHR) with epilepsy. Method: Animals were randomly dividedinto 4 groups: control Wistar, Wistar with epilepsy, control SHR and SHR with epilepsy. The pilocarpine modelof epilepsy was used in this experiement. After spontaneous recurrent seizures, all animals were perfusedand their brains processed for histological analysis through Nissl and neo-Timm methods. Results: In theWistar rats with epilepsy we observed cell loss in hippocampal subfields CA1, CA3 and hilus of the dentategyrus when compared with control animals. In the SHR with epilepsy we observed hippocampal formationatrophy with ventricular dilatation. No morphological alterations were observed in SHR and Wistar controlrats. The neo-Timm staining of hippocampal formation has shown supragranular sprouting in Wistar andSHR with epilepsy. Conclusion: We found neuropathological alterations in hippocampal formation in Wis-tar with epilepsy and SHR with epilepsy, suggesting that epilepsy per se or associated to hypertention areable to cause neuronal damage.KEY WORDS: epilepsy, arterial hypertension, seizure, pilocarpine.

Morphological and electrophysiological properties of pyramidal-like neurons in the stratum oriens of Cornu ammonis 1 and Cornu ammonis 2 area of Proechimys.

Proechimys (Rodentia: Echimyidae) is a neotropical rodent of the Amazon region that has been successfully colonized in the laboratory and used for experimental medicine. Preliminary studies indicated that Proechimys (casiragua) rodents express an atypical resistance to developing a chronic epileptic condition in common models of temporal lobe epilepsy. Moreover, previous investigation of our laboratory described a remarkably different Proechimys cytoarchitecture organization of the hippocampal CA2 subfield. In the present study, we investigated the intrinsic neuronal properties and morphological characteristics of the Proechimyss hippocampal pyramidal neurons of the CA1 and CA2 areas. A comparative approach was performed using neurons recorded in Wistar rats. A striking finding in Proechimys rodents was the presence of large pyramidal-like neurons throughout the stratum oriens from CA2 to CA1 area. In order to confirm such distinctive feature of the Proechimyss hippocampus, we performed Nissl staining and immunohistochemistry for neurofilament protein SM311. CA2 pyramidal neurons in the stratum pyramidale of Proechimys exhibited a significantly higher input resistance and lower time constant when compared to corresponding cell groups in the same area of the Wistar rats. This newly identified population of pyramidal-shaped neurons in stratum oriens of Proechimys exhibited distinct electrophysiological and morphological properties. This included larger capacitance, lower input resistance, larger rheobase, long latency to first action potential and slower firing frequency. In addition, the apical dendrites of these neurons were oriented in parallel to apical dendrites of regular pyramidal neurons in stratum pyramidale. Moreover, these neurons were immunoreactive to SM311 as the majority of the neurons of the pyramidal layer. The functional role of these hippocampal neurons of the rodent Proechimys deserves further investigation.

Positive impact of omega-3 fatty acid supplementation in a dog with drug-resistant epilepsy: a case study.

Epilepsy is the most common neurological disorder in both dogs and humans. Although the pharmacological options for treatment of epilepsies have increased, it has been reported that two-thirds of dogs with epilepsy are refractory to antiepileptic drug therapy. To our knowledge, there are no experimental studies in the literature that show an effect of omega-3 supplementation on epilepsy in dogs. Our case study describes the effectiveness of daily intake of a moderate amount of fish oil in a case of canine epilepsy.