Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. Results: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.

Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known to date. While its plasma or serum concentrations are elevated in some forms of experimental and human hypertension, this is not a consistent finding in all forms of hypertension. Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9), which degrade collagen type IV of the vascular basement membrane, are responsible for vascular remodeling, inflammation, and atherosclerotic complications, including in type 2 diabetes (T2D). In our study, we compared concentrations of ET-1, MMP-2, and MMP-9 in pre-hypertensive (PHTN) and hypertensive (HTN) T2D patients with those of healthy normotensive controls (N). ET-1, MMP-2, and MMP-9 were measured by ELISA. Concentrations of ET-1 in PHTN and N were very similar, while those in HTN were significantly higher. Concentrations of MMP-2 and MMP-9 in PHTN and HTN were also significantly higher compared to N. An interesting result in our study is that concentrations of MMP-2 and MMP-9 in HTN were lower compared to PHTN. In conclusion, we showed that increased production of ET-1 in patients with T2D can lead to long-lasting increases in blood pressure (BP) and clinical manifestation of hypertension. We also demonstrated that increased levels of MMP-2 and MMP-9 in pre-hypertensive and hypertensive patients with T2D mainly reflect the early vascular changes in extracellular matrix (ECM) turnover.

Background: Aging affects anxiety levels in rats while the pineal gland, via its hormone melatonin, could modulate their inherited life “clock.” The present study aimed to explore the impact of plasma melatonin deficiency on anxiety responses and the possible involvement of the hypothalamic-pituitary-adrenocortical (HPA) axis and heat shock proteins (Hsp) 70 and 90 in the frontal cortex (FC) and the hippocampus in young adult, middle-aged and elderly rats with pinealectomy. Results: Melatonin deficiency induced at different life stages did not affect the lifespan of rats. Pinealectomy abolished the circadian rhythm of motor activity, measured for 48 h in the actimeter, in young adult but not in middle-aged rats. Pinealectomy reduced the motor activity of the young adult rats during the dark phase and impaired the diurnal activity variations of old rats. The same generations (3- and 18 month-old rats with pinealectomy) had lower anxiety levels than the matched sham groups, measured in three tests: elevated-plus maze, light–dark test, and novelty-suppressed feeding test. While the activity of the HPA axis remained intact in young adult and middle-aged rats with melatonin deficiency, a high baseline corticosterone level and blunted stress-induced mechanism of its release were detected in the oldest rats. Age-associated reduced Hsp 70 and 90 levels in the FC but not in the hippocampus were detected. Pinealectomy diminished the expression of Hsp 70 in the FC of middle-aged rats compared to the matched sham rats. Conclusions: Our results suggest that while melatonin hormonal dysfunction impaired the motor activity in the actimeter and emotional behavior in young adult and elderly rats, the underlying pathogenic mechanism in these generations might be different and needs further verification.