Treatment with melatonin after status epilepticus attenuates seizure activity and neuronal damage but does not prevent the disturbance in diurnal rhythms and behavioral alterations in spontaneously hypertensive rats in kainate model of temporal lobe epilepsy

The role of the melatoninergic system in epilepsy and comorbid psychiatric disorders

“…The intact SHR is characterized by typical behavioral, electrophysiological, and biochemical abnormalities -which are also evident in epileptic rats -such as attention deficit, impulsiveness, deficient sustained attention, and monoamine deficits in the frontal cortex and hippocampus, suggesting that this strain might be used also as a relevant model of ADHD comorbidity (Tchekalarova, 2014). In addition, we recently demonstrated that long-term treatment with melatonin for KA-induced epileptogenesis produces different effects in Wistar rats and SHRs; the finding supported the hypothesis that 21 the underlying mechanisms of behavioral comorbidities in epilepsy differ in these two rat strains (Tchekalarova et al, 2013;Petkova et al, 2014). Indeed, while seizure frequency in epileptic SHRs remained significantly decreased even after discontinuation of melatonin, in…”

“…The anticonvulsant and neuroprotective effects of melatonin have been verified in the chronic amygdala kindling model of partial epilepsy in rats (Mevissen et al, 1998) and the KA model of temporal lobe epilepsy (Tchekalarova et al 2013;Petkova et al, 2014).…”

“…In addition, whereas the administration of melatonin to Wistar rats produced a beneficial effect on behavioral and biochemical complications, such as hyperactivity, anxiety, depression, memory deficit, and low hippocampal 5-HT , longterm treatment failed to positively affect the behavioral and memory deficits or improve the disturbed diurnal behavioral rhythms in epileptic SHRs (Petkova et al, 2014). However, melatonin was neuroprotective in the CA1 hippocampal area and the piriform cortex in both rat strains, suggesting a positive relationship between anti-seizure efficacy and neuroprotection.…”

“…Continuous administration of melatonin had disease-modifying effects on neuronal damage and behavioral disturbances in different models of neurodegenerative disorders: long-term melatonin treatment (4 mg/kg/day, via drinking water for 29 days) attenuated behavioral complications associated with increased motor activity and anxiety in a mouse model of ischemic stroke (Kilic et al, 2008), but repeated melatonin administration was unable to prevent kainic acid (KA)-induced epileptogenesis in Wistar rats and spontaneously hypertensive rats (SHRs), although it did exert neuroprotection in specific brain areas and restored the anxiety response during the chronic epileptic phase (Tchekalarova et al, 2013;Petkova et al, 2014).…”

Effect of endurance training on seizure susceptibility, behavioral changes and neuronal damage after kainate-induced status epilepticus in spontaneously hypertensive rats

“…10A-F) (Tchekalarova et al, 2010;Petkova et al, 2014). Statistical analysis of data by one-way ANOVA indicated a significant neuronal damage in the CA1 (septal, septo-temporal and temporal) (t¼ 23.855, p¼ 0.002), CA3a (septal, septo-temporal and temporal) (t¼ 12.936, p ¼0.006) and CA3c (septal, septo-temporal and temporal) (t ¼12.411, p¼ 0.051) areas of the hippocampus, as well as in the hilus of the dentate gyrus (septal, septo-temporal and temporal) (t¼40.064, p ¼0.001) in the KA-veh group (Fig.…”