Resumo

Objectives: An increased incidence of cerebral palsy (CP), a developmental neurological disorder, has been associated with several pre, peri or postnatal insults such as oxygen deprivation and maternal infections. In the present study, the effects of maternal exposure to low doses of bacterial endotoxin (lipopolysaccharide, LPS) on balance and coordination were examined in young rats. Prenatal exposure to LPS was also associated to perinatal asphyxia (PA) with or without subsequent sensorimotor restriction (SR). Materials and Methods: For gestational LPS treatment, timed pregnant Wistar rats were divided into 2 groups: Group 1 (n = 10), LPS injected rats (200 µg/kg diluted in 100 µL of saline) and Group 2 (n = 10), saline injected rats (100 µL). The pregnant rats were injected with LPS or saline at 12-hour intervals until the end of gestation. On the day of birth (P0) half of the pups born from both group of mothers were subjected to PA. For this procedure, rat pups were placed for 20 min in a temperature controlled chamber (37º C ± 1º C) with a flow of 9 L/min of 100% N2. At P2 half of the animals of each group were submitted to SR (16 h/day) until P28. The pup’s hind limbs were immobilized in an extended position by a support made of epoxy resin. Accordingly to these procedures, male pups were randomly assigned to eight different groups (n = 6): rats exposed to saline during the embryonic period (CT); rats exposed to LPS; PA LPS+PA; LPS+PA; saline and sensorimotor restriction (SR); LPS+SR; saline, anoxia and sensorimotor restriction (PA+SR); LPS+PA+SR. All procedures were approved by the Ethical Committee at the UFRGS (no 2008189). Motor balance and coordination were evaluated on P29 using a Rotarod at a speed of 30 rpm. The time spent by the animal on the Rotarod was considered as the latency to fall. Data were analyzed using three-way analysis of variance (ANOVA) followed by post hoc Duncan test. Results: CT rats performed the test significantly better than any other group, whereas, any restricted rat, independently of the combination of treatments, showed the worst performances. SR (13.55 ± 9.56), LPS+SR (9.25 ± 7.35), PA+SR (23.37 ± 19.86), and LPS+PA+SR (16.88 ± 15.02) rats remained a shorter time period on the Rotarod when compared to CT (142.74 ± 11.06; P<0.001). LPS (68.01 ±24.64), PA (99.18 ± 16.26) and LPS+PA (70.57 ± 15.09) rats presented similar performances between them and significantly better than the all restricted rat (P<0.05) but worst than CT (P<0.05). Conclusion: These results suggest that prenatal exposure to LPS, PA or SR alone or in combination have various degrees of consequences on balance and coordination of young rats. These data strengthen the idea that asphyxia and/or maternal infections during pregnancy can contribute to sensorimotor integration and that early experience-dependent movements play an important role motor behavior contributing to the development of impairments of motor function and coordination observed in patients with CP. This research was supported by CNPq, CAPES (Brazil).