Fulvio A. Scorza

Effect of physical exercise on seizure occurrence in a model of temporal lobe epilepsy in rats

Although the favorable effect of physical fitness on general health is unquestionable, physical exercise and fitness programs in patients with epilepsy are still a matter of controversy. Little objective evidence regarding the effect of exercise on seizure frequency and severity has been reported. One sought to clarify the relationship between exercise and epilepsy in an animal model of temporal lobe epilepsy (the pilocarpine model of epilepsy). To evaluate the effect of an aerobic physical program on seizure frequency, 29 epileptic animals were continuously monitored during 24 h for 135 days after the first spontaneous recurrent seizure (SRS) and divided into three groups. The first group (N = 14) was submitted to an aerobic exercise program (training group). The second group (N = 7) was maintained in the treadmill for the same time as the training group without being submitted to physical exercise (sham group). The third group (N = 8) served as control. The behavioral observation was divided in three periods of 45 days. The first period was used to determine the number of seizures before physical training program. The second period was utilized to determine the number of seizures during the physical training program. The third period was used to analyze the frequency of seizures after the physical training program. The mean frequency of seizures in the control and sham groups increased significantly from period 1 to period 2 and from period 1 to period 3. However, in the training group, the frequency of seizures did not change significantly between the three periods of 45 days of observation. When the same periods of the three groups were analyzed together, a significant reduction in seizure frequency was observed comparing the training group with the control and sham groups during the period of physical training. The data presented in this study suggest that physical exercise is not a seizure-inducing factor in this experimental model of epilepsy.

The course of untreated seizures in the pilocarpine model of epilepsy

The course of untreated epilepsy is not well established. This study uses a model of chronic limbic epilepsy (pilocarpine model of epilepsy) to determine the pattern of occurrence of seizures in untreated animals. Following pilocarpine administration, 21 rats were monitored continuously with a video system for 135 days after the first spontaneous seizure. Animals showed a great variability in seizure numbers and were divided in two subgroups presenting either a low frequency of seizures (n = 9 animals presenting ten or less seizures in the first 15 days of observation) or a high frequency of seizures (n = 12 animals presenting more than ten seizures during this period). Animals with low number of seizures during the first 15 days of observation showed a significant increase in seizure frequency in the following period of analysis (until 105 days). On the other hand, those with initial high number of seizures showed significant changes in seizure frequency only in the first 2 months. The duration of each spontaneous seizure did not change significantly over time. These findings show that in untreated epilepsy there is a maturation process in the early stages and this accelerating process can be of predictive value for the treatment of epilepsy.

The pilocarpine model of epilepsy: what have we learned?

The systemic administration of a potent muscarinic agonist pilocarpine in rats promotes sequential behavioral and electrographic changes that can be divided into 3 distinct periods: (a) an acute period that built up progressively into a limbic status epilepticus and that lasts 24 h, (b) a silent period with a progressive normalization of EEG and behavior which varies from 4 to 44 days, and (c) a chronic period with spontaneous recurrent seizures (SRSs). The main features of the SRSs observed during the long-term period resemble those of human complex partial seizures and recurs 2-3 times per week per animal. Therefore, the pilocarpine model of epilepsy is a valuable tool not only to study the pathogenesis of temporal lobe epilepsy in human condition, but also to evaluate potential antiepileptogenic drugs. This review concentrates on data from pilocarpine model of epilepsy.

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.

Physical Activity and Epilepsy Proven and Predicted Benefits

Epilepsy is a common disease found in 2% of the population, affecting people from all ages. Unfortunately, persons with epilepsy have previously been discouraged from participation in physical activity and sports for fear of inducing seizures or increasing seizure frequency. Despite a shift in medical recommendations toward encouraging rather than restricting participation, the stigma remains and persons with epilepsy continue to be less active than the general population. For this purpose, clinical and experimental studies have analysed the effect of physical exercise on epilepsy. Although there are rare cases of exercise-induced seizures, studies have shown that physical activity can decrease seizure frequency, as well as lead to improved cardiovascular and psychological health in people with epilepsy. The majority of physical activities or sports are safe for people with epilepsy to participate in with special attention to adequate seizure control, close monitoring of medications, and preparation of family or trainers. The evidence shows that patients with good seizure control can participate in both contact and non-contact sports without harmfully affecting seizure frequency. This article reviews the risks and benefits of physical activity in people with epilepsy, discusses sports in which persons with epilepsy may participate, and describes the positive effect of physical exercise in experimental models of epilepsy.

Early Exercise Promotes Positive Hippocampal Plasticity and Improves Spatial Memory in the Adult Life of Rats

There is a great deal of evidence showing the capacity of physical exercise to enhance cognitive function, reduce anxiety and depression, and protect the brain against neurodegenerative disorders. Although the effects of exercise are well documented in the mature brain, the influence of exercise in the developing brain has been poorly explored. Therefore, we investigated the morphological and functional hippocampal changes in adult rats submitted to daily treadmill exercise during the adolescent period. Male Wistar rats aged 21 postnatal days old (P21) were divided into two groups: exercise and control. Animals in the exercise group were submitted to daily exercise on the treadmill between P21 and P60. Running time and speed gradually increased over this period, reaching a maximum of 18 m/min for 60 min. After the aerobic exercise program (P60), histological and behavioral (water maze) analyses were performed. The results show that early‐life exercise increased mossy fibers density and hippocampal expression of brain‐derived neurotrophic factor and its receptor tropomyosin‐related kinase B, improved spatial learning and memory, and enhanced capacity to evoke spatial memories in later stages (when measured at P96). It is important to point out that while physical exercise induces hippocampal plasticity, degenerative effects could appear in undue conditions of physical or psychological stress. In this regard, we also showed that the exercise protocol used here did not induce inflammatory response and degenerating neurons in the hippocampal formation of developing rats. Our findings demonstrate that physical exercise during postnatal development results in positive changes for the hippocampal formation, both in structure and function.

Evaluation of physical exercise habits in Brazilian patients with epilepsy

In this study we present data from a survey that aimed to assess the physical activity of a sample of adult outpatients with epilepsy. One hundred adult outpatients of both sexes with epilepsy answered a survey addressing exercise habits. Fifty-eight males and forty-two females participated in this study. The mean age of onset of seizures was 18.6 years and the mean duration of epilepsy was 16.1 years. Sixty patients had controlled or rare seizures, 8 infrequent seizures, 17 frequent seizures, and 11 very frequent seizures. Eighty-six had partial epilepsy and only 3 had abnormal neurological examinations. Of the total, 51 engaged in physical activity, 85 did not believe that sports precipitate seizures, and 15 were forbidden by their physicians to engage in physical activities. Moreover, 14 were cautioned against participation in sports by their relatives and friends. Eight-four patients had never experienced seizures during physical exercise, 36 believed that physical activity has a positive influence on treatment, and only 1 related injuries associated with seizures. Forty-five are afraid of having seizures during exercise because the seizures might attract the attention of others and they would make fools of themselves. Our data show that although most of our patients do not regularly engage in physical activity, they believe that it might improve medical treatment.

Whole transcriptome analysis of the hippocampus: toward a molecular portrait of epileptogenesis

BackgroundUncovering the molecular mechanisms involved in epileptogenesis is critical to better understand the physiopathology of epilepsies and to help develop new therapeutic strategies for this prevalent and severe neurological condition that affects millions of people worldwide.ResultsChanges in the transcriptome of hippocampal cells from rats subjected to the pilocarpine model of epilepsy were evaluated by microarrays covering 34,000 transcripts representing all annotated rat genes to date. Using such genome-wide approach, differential expression of nearly 1,400 genes was detected during the course of epileptogenesis, from the early events post status epilepticus (SE) to the onset of recurrent spontaneous seizures. Most of these genes are novel and displayed an up-regulation after SE. Noteworthy, a group of 128 genes was found consistently hyper-expressed throughout epileptogenesis, indicating stable modulation of the p38MAPK, Jak-STAT, PI3K, and mTOR signaling pathways. In particular, up-regulation of genes from the TGF-beta and IGF-1 signaling pathways, with opposite effects on neurogenesis, correlate with the physiopathological changes reported in humans.ConclusionsA consistent regulation of genes functioning in intracellular signal transduction regulating neurogenesis have been identified during epileptogenesis, some of which with parallel expression patterns reported in patients with epilepsy, strengthening the link between these processes and development of epilepsy. These findings reveal dynamic molecular changes occurring in the hippocampus that may serve as a starting point for designing alternative therapeutic strategies to prevent the development of epilepsy after acquired brain insults.

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.

Evaluation of physical activity habits in patients with posttraumatic stress disorder.

OBJECTIVE In this study, we present data from a survey that aimed to assess the physical activity habits of adult Brazilian patients with Posttraumatic Stress Disorder. METHOD Fifty male and female patients with Posttraumatic Stress Disorder participated in this study. The mean age at onset was 37±12 years, and the mean time between diagnosis and follow-up was 3.6±4.2 years. RESULTS Substantial changes in physical activity habits were observed following the onset of PTSD. While more than half of the patients participated in physical activities prior to Posttraumatic Stress Disorder onset, there was a significant reduction in their participation afterwards. The justifications for stopping physical activities or sport participation were lack of time and lack of motivation. DISCUSSION Several studies have shown that physical exercise decreases reverts symptoms of psychiatric disorders such as depression, anxiety and social isolation. We could therefore hypothesize that patients with Posttraumatic Stress Disorder who exercise should experience the same benefits. CONCLUSION Our findings demonstrated that patients with Posttraumatic Stress Disorder have low levels of participation in sports or physical activities.