Summary:Purpose: Animal models are useful for the study of status epilepticus (SE)-induced epileptogenesis and neurological sequelae, especially during early brain development. Here, we show several permanent abnormalities in animals subjected to multiple SE during early development.Methods: Wistar pup rats (7 to 9 days old) were subjected to three consecutive episodes of SE induced by systemic pilocarpine injections. To study the long-lasting consequences of early-induced SE, chronic electroencephalographic recordings were made from the hippocampus and cortex and several behavioral tests (inhibitory step-down avoidance, rota-rod, open field, elevated plus-maze, and Skinner box) were performed at postnatal days 30 to 90. We also investigated in vitro electrophysiological responses of the CA 1 area using extracellular recordings in hippocampal slices. A histological analysis was done using cresyl violet staining 24 hours and several months after SE induction. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL staining) 24 hours after the last SE episode.Results: Electroencephalographic recordings from 30-to 90-day-old rats that had been subjected to multiple SE episodes in early life showed marked changes compared with those from nontreated controls. These included frequent episodes of continuous complex spiking activity and high-voltage ictal discharges, with a small percentage of these rats presenting spontaneous behavioral seizures. These animals also presented evidence of severe cognitive deficit in adulthood. In vitro, a persistent hyperexcitability of the CAI area was detected in experimental animals. Histological analysis of the brains did not reveal any major long-term pathological changes. Nevertheless, an increased number of TUNEL-positive nuclei were present in some animals in both the hippocampus and the thalamus.Conclusions: These data show persistent abnormalities in animals subjected to multiple SE episodes during early postnatal development. SE may result in important plastic changes in critical periods of brain maturation leading to long-lasting epileptogenesis, as manifested by electrographic epileptiform discharges, behavioral deficits, and in vitro hyperexcitability of hippocampal networks.

We evaluated if repeated stress modulates mucociliary clearance and inflammatory responses in airways of guinea pigs (GP) with chronic inflammation. The GP received seven exposures of ovalbumin or saline 0.9%. After 4th inhalation, animals were submitted to repeated forced swim stressor protocol (5x/week/2 weeks). After 7th inhalation, GP were anesthetized. We measured transepithelial potential difference, ciliary beat frequency, mucociliary transport, contact angle, cough transportability and serum cortisol levels. Lungs and adrenals were removed, weighed and analyzed by morphometry. Ovalbumin-exposed animals submitted to repeated stress had a reduction in mucociliary transport, and an increase on serum cortisol, adrenals weight, mucus wettability and adhesivity, positive acid mucus area and IL-4 positive cells in airway compared to non-stressed ovalbumin-exposed animals (p<0.05). There were no effects on eosinophilic recruitment and IL-13 positive cells. Repeated stress reduces mucociliary clearance due to mucus rheological-property alterations, increasing acid mucus and its wettability and adhesivity. These effects seem to be associated with IL-4 activation.

Background: Cerebral Palsy (CP) is characterised by variable difficulties in muscular action, resulting in inability of the individual to perform functional movement. An option to provide functionality to the individual with CP is the use of computer innovation. The aim of this paper was to verify if there was any performance improvement in a task performed in a virtual environment and if there was transfer to the task performed in the real environment and vice versa in this population. Methods: A computer program was developed comprising a motor task, but with two possibilities of user interaction: a) concrete interface (with physical contact): in which the individual touches the computer screen to finish the task and b) abstract interface (no physical contact): in which the individual performs a hand movement in front of the Kinect device. Participants were split into two groups. The experimental group consisted of 28 individuals with CP within the ages of 6 and 15 years old. The control group included 28 typically developing individuals mirroring the age and sex of the experimental group. Results: Individuals from both groups were able to improve task performance and retain acquired information. The CP group presented worse performance than the control group in all phases of the study. Further findings showed that the CP group presented better performance in the abstract interface than in the concrete interface, whereas, in the control group, the opposite occurred: their best performance was in the concrete.

Mechanisms involved in stress-induced asthmatic alterations have been poorly characterised. We assessed whether inducible nitric oxide synthase (iNOS) inhibition modulates the stress-amplified lung parenchyma responsiveness, oxidative stress and extracellular matrix remodelling that was previously increased by chronic lung inflammation. Guinea pigs were subjected to 7 exposures to ovalbumin (1–5 mg/ml) or saline (OVA and SAL groups) over 4 weeks. To induce behavioural stress, animals were subjected to a forced swimming protocol (5 times/week, over 2 weeks; SAL-Stress and OVA-Stress groups) 24 h after the 4th inhalation. 1400W (iNOS-specific inhibitor) was administered intraperitoneally in the last 4 days of the protocol (SAL-1400W, OVA-1400W, SAL-Stress+1400W and OVA-Stress+1400W groups). Seventy-two hours after the last inhalation, animals were anaesthetised and exsanguinated, and adrenal glands were removed. Lung tissue resistance and elastance were evaluated by oscillatory mechanics and submitted for histopathological evaluation. Stressed animals had higher adrenal weights compared to non-stressed groups, which were reduced by 1400W treatment. Behavioural stress in sensitised animals amplified the resistance and elastance responses after antigen challenge, numbers of eosinophils and iNOS+ cells, actin content and 8-iso-PGF2α density in the distal lung compared to the OVA group. 1400W treatment in ovalbumin-exposed and stressed animals reduced lung mechanics, iNOS+ cell numbers and 8-iso-PGF2α density compared to sensitised and stressed animals that received vehicle treatment. We concluded that stress amplifies the distal lung constriction, eosinophilic inflammation, iNOS expression, actin content and oxidative stress previously induced by chronic lung inflammation. iNOS-derived NO contributes to stress-augmented lung tissue functional alterations in this animal model and is at least partially due to activation of the oxidative stress pathway.