Testicular androgens determining the incidence of spike-wave discharges in taiep rats: A model of H-ABC leukodystrophy.

Absence seizures are characterized as a generalized type of epilepsy that occurs during childhood. Importantly, absence seizures in children often discontinue after puberty. There is limited availability of animal models in which electroencephalography (EEG) can be performed in the long term; however, two absence seizure models, GAERS and WAG/Rij albino rats, are available. The taiep rat is a myelin mutant rat with tubulinopathy due to a tubulin ß 4A gene mutation and characteristic spike-wave discharges (SWDs) that mimic absence seizure epilepsy in humans and the above rat models. This study aimed to analyze spike-wave discharges after an orchiectomy was performed on postnatal day (PND) 2 or PND 90 in adult rats; and SWDs was recorded in both groups on PND 104. The results suggest that androgens play a critical role in susceptibility to SWDs. In fact, orchiectomy during the neonatal period significantly reduced the frequency of spike-wave discharges. However, if an orchiectomy was performed in adulthood, then SWDs were significantly increased. The mean duration of spike-wave discharges did not differ among the groups tested. Acute administration of testosterone (1 mg/kg) did not change the frequency or duration of spike-wave discharges in the control group or both orchiectomized groups. Overall, this study is the first to show a dichotomic influence of testicular androgens on spike-wave discharges. These findings will have implications in children with this type of generalized epilepsy and may explain the disappearance of absence epilepsy in two-thirds of patients after puberty.

Gemfibrozil attenuates the inflammatory response and protects rats from abdominal sepsis.

Sepsis is a serious condition characterized by an infectious process that induces a severe systemic inflammatory response. In this study, the effects of gemfibrozil (GFZ) on the inflammatory response associated with abdominal sepsis were investigated using a rat model of cecal-ligation and puncture (CLP). Male Wistar rats were randomly divided into three groups: Sham-operated group (sham), where laparotomy was performed, the intestines were manipulated, and the cecum was ligated but not punctured; control group, subjected to CLP; and GFZ group, which received GFZ prior to undergoing CLP. The groups were then subdivided into three different time-points: 2, 4 and 24 h, indicating the time at which blood samples were obtained for analysis. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were determined. The LDH, AST and ALT values were significantly elevated following CLP compared with those in the sham group, and GFZ treatment was able to reduce these elevations. GFZ also reduced the sepsis-induced elevations of TNF-α and IL-1. In conclusion, GFZ treatment was able to attenuate the inflammatory response associated with CLP-induced sepsis, by diminishing the release of inflammatory cytokines, thereby reducing tissue injury and oxidative stress.