A role of Na+, K+ -ATPase in spatial memory deficits and inflammatory/oxidative stress after recurrent concussion in adolescent rats.

Sports-related concussions are particularly common during adolescence, and there is insufficient knowledge about how recurrent concussions in this phase of life alter the metabolism of essential structures for memory in adulthood. In this sense, our experimental data revealed that seven recurrent concussions (RC) in 35-day-old rats decreased short-term and long-term memory in the object recognition test (ORT) 30 days after injury. The RC protocol did not alter motor and anxious behavior and the immunoreactivity of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Recurrent concussions induced the inflammatory/oxidative stress characterized here by increased glial fibrillary acidic protein (GFAP), interleukin 1ß (IL 1ß), 4-hydroxynonenal (4 HNE), protein carbonyl immunoreactivity, and 2',7'-dichlorofluorescein diacetate oxidation (DCFH) levels and lower total antioxidant capacity (TAC). Inhibited Na+,K+-ATPase activity (specifically isoform α2/3) followed by Km (Michaelis-Menten constant) for increased ATP levels and decreased immunodetection of alpha subunit of this enzyme, suggesting that cognitive impairment after RC is caused by the inability of surviving neurons to maintain ionic gradients in selected targets to inflammatory/oxidative damage, such as Na,K-ATPase activity.

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

PURPOSE: We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus. METHODS: Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies. RESULTS: The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group. CONCLUSIONS: We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Impacto da exposição pós-natal crônica ao estresse sobre o comportamento ansiogênico de ratos jovens induzidos pela desnutrição in utero / Impact of chronic postnatal exposure to stress on the anxiogenic behavior of young rats induced by undernutrition in utero

Exposure to stress and undernutrition alone are important risk factors in the development of neurobehavioral disorders. However, few studies focus on how chronic postnatal stress affects adaptive behavioral response to undernutrition in utero. OBJECTIVE: to investigate whether chronic postnatal stress exposure constitutes a risk factor in addition to undernutrition in utero to developing neurobehavioral disorders in young rats. METHODS: we evaluated the overall activity in the Open Field, and anxiety in the Elevated Plus Maze of male Wistar rats (35 days) from dams submitted or not to food restriction (50%) throughout pregnancy and exposed or not to restraint stress (single sections 1 h/day, 5 days/week for 2 weeks from weaning). RESULTS: postnatal stress and undernutrition in utero, alone and in combination, did not cause changes to the young rats behavior, except for a decrease of locomotion in the central and middle zone of the Open Field in the offsprings subjected to undernutrition in utero. The postnatal stress, alone and in combination, did not change the activity in Elevated Plus Maze. However, the time spent in the open arms decreased while the time in the closed arms increased in undernourished rats in utero. The anxiety index was decreased by undernutrition in utero. CONCLUSION: the absence of behavioral changes in young rats exposed to undernutrition in utero in association with chronic postnatal stress suggests that the physiological changes that lead to anxiogenic condition induced by undernutrition in utero alone take place mainly during the postnatal development

Exposição ao estresse e desnutrição, isoladamente, são importantes fatores de risco no desenvolvimento de transtornos neurocomportamentais. Entretanto, poucos estudos focam como o estresse pós-natal crônico afeta a resposta comportamental adaptativa à desnutrição in utero. OBJETIVO: investigar se a exposição pós-natal crônica ao estresse constitui-se em fator de risco adicional à desnutrição in utero para o desenvolvimento de transtornos neurocomportamentais em ratos jovens. MÉTODOS: avaliou-se a atividade geral, em Campo Aberto, e a ansiedade, no Labirinto em Cruz Elevado, de ratos machos Wistar (35 dias) provenientes de ratas submetidas ou não à restrição alimentar (50%) durante toda a prenhez, e expostos ou não ao estresse de contenção (seções únicas 1 h/dia, 5 dias/semana, durante 2 semanas a partir do desmame). RESULTADOS: o estresse pós-natal e a desnutrição in utero, isoladamente e em associação, não determinaram alterações no comportamento de ratos jovens, exceto pela diminuição da locomoção na zona central e mediana do Campo Aberto em proles submetidas à desnutrição in utero. O estresse pós-natal, isoladamente e em associação, não alterou a atividade no Labirinto em Cruz Elevado. Entretanto, o tempo de permanência nos braços abertos diminuiu enquanto o tempo nos braços fechados aumentou em ratos desnutridos in utero. O índice de ansiedade foi diminuído pela desnutrição in utero. CONCLUSÃO: a ausência de alterações comportamentais em ratos jovens expostos à desnutrição in utero em associação ao estresse pós-natal crônico sugere que as alterações fisiológicas que levam à condição ansiogênica induzida pela desnutrição in utero, isoladamente, têm lugar principalmente durante o desenvolvimento pós-natal

Influence of acute treatment with sibutramine on the sympathetic neurotransmission of the young rat vas deferens.

The effects of acute treatment with sibutramine on the peripheral sympathetic neurotransmission in vas deferens of young rats were still not evaluated. Therefore, we carried out this study in order to verify the effects of acute sibutramine treatment on the neuronal- and exogenous agonist-induced contractions of the young rat vas deferens. Young 45-day-old male Wistar rats were pretreated with sibutramine 6 mg/kg and after 4h the vas deferens was used for experiment. The acute treatment with sibutramine was able to increase the potency (pD2) of noradrenaline and phenylephrine. Moreover, the efficacy (Emax) of noradrenaline was increased while the efficacy of serotonin and nicotine were decreased. The maximum effect induced by a single concentration of tyramine was diminished in the vas deferens from treated group. Moreover, the leftward shift of the noradrenaline curves promoted by uptake blockers (cocaine and corticosterone) and ß-adrenoceptor antagonist (propranolol) was reduced in the vas deferens of treated group. The initial phasic and secondary tonic components of the neuronal-evoked contractions of vas deferens from treated group at the frequencies of 2 Hz were decreased. Moreover, only the initial phasic component at 5 Hz was diminished by the acute treatment with sibutramine. In conclusion, we showed that the acute treatment with sibutramine in young rats was able to affect the peripheral sympathetic nervous system by inhibition of noradrenaline uptake and reduction of the neuronal content of this neurotransmitter, leading to an enhancement of vas deferens sensitivity to noradrenaline.