Effects of different physical exercise programs on susceptibility to pilocarpine-induced seizures in female rats

Abstract

In epilepsy, the most common serious neurological disorder worldwide, several investigations in both humans and animals have shown the effectiveness of physical exercise programs as a complementary therapy. Among the benefits demonstrated, regular exercise can decrease the number of seizures as well as improve cardiovascular and psychological health in people with epilepsy. While many studies in animals have been performed to show the beneficial effects of exercise, they exclusively used male animals. However, females are also worthy of investigation because of their cyclical hormonal fluctuations and possible pregnancy. Considering the few animal studies concerning seizure susceptibility and exercise programs in females, this study aimed to verify whether exercise programs can interfere with seizure susceptibility induced by pilocarpine in adult female Wistar rats. Animals were randomly divided into three groups: control, forced, and voluntary (animals kept in a cage with a wheel). After the final exercise session, animals received a pilocarpine hydrochloride (350 mg/kg i.p.; Sigma) injection to induce seizures. To measure the intensity of pilocarpine-induced motor signs, we used a scale similar to that developed by Racine (1972) in the kindling model. During a 4-h period of observation, we recorded latency for first motor signs, latency for reaching SE, number of animals that developed SE, and intensity of pilocarpine-induced motor signs. No difference was observed among groups in latency for first motor signs and in the number of animals that developed SE. Although the voluntary group presented more intense motor signs, an increased latency for developing SE was observed compared with that in forced and control groups. Our behavioral results are not enough to explain physiological and molecular pathways, but there are mechanisms described in literature which may allow us to propose possible explanations. Voluntary exercise increased latency to SE development. Further investigation is necessary to elucidate the pathways involved in these results, while more studies should be performed regarding gender specific differences.

The Potential Role of Previous Physical Exercise Program to Reduce Seizure Susceptibility: A Systematic Review and Meta-Analysis of Animal Studies

“…Of the studies, 10 (337 animals) analyzed the behavior manifestation following chemoconvulsants. Of 7 studies reporting latency for the first motors signs or first seizure, four studies showed increased latency (28,29,35,41) and three studies did not find significant alterations following exercise (34,40,42).…”

“…In relation to the intensity of motor signs, six of ten investigations reported lower intensity following physical exercise (28,(37)(38)(39)(40)(41), one registered higher intensity in voluntary but not in forced exercise (42), one reported no significant difference (29), and two did not analyze this parameter (34,35).…”

“…Only studies that used exercise intervention before SE induction were included. Six studies used a treadmill (28)(29)(30)(31)(32)(33), five studies used swimming (34)(35)(36)(37)(38), two studies used a running wheel (39,40), and two studies used combined exercise: one applied treadmill and swimming (41), and the other used running wheel and treadmill (42). The total duration of exercise ranged between 21 and 90 days.…”

“…The frequency ranged from five to seven times a week, and two studies did not report session frequency and duration (39,40). Among the chemoconvulsants used in the selected studies, two used pentylenetetrazol (34,35), five used penicillin (30)(31)(32)(33)36), four used kainic acid (37)(38)(39)(40), three pilocarpine (28,41,42), and one homocysteine (29). See details in Table 1.…”

“…From 15 included studies, 13 demonstrated that physical exercise reduced seizure susceptibility induced by different chemoconvulsants such as homocysteine thiolactone (HCT), pentylenetetrazole (PTZ), penicillin, kainite, or pilocarpine (28)(29)(30)(31)(32)(34)(35)(36)(37)(38)(39)(40)(41) and two studies revealed no significant difference in seizure susceptibility between the exercise and control groups (33,42), which suggests a potential protective effect of exercise against seizure susceptibility.…”