The presence of oxidative stress in immature brain has been demonstrated during the acute phase of status epilepticus (SE). The knowledge regarding the long periods of survival after SE is not unequivocal, lacking direct evidence. To examine the presence and time profile of oxidative stress, its functional effect on mitochondria and the influence of an antioxidant treatment in immature rats during epileptogenesis, status epilepticus (SE) was induced in immature 12-day-old rats by Li-pilocarpine and at selected periods of the epileptogenesis; rat pups were subjected to examinations. Hydroethidine method was employed for detection of superoxide anion (O2.-), 3-nitrotyrosine (3-NT), and 4-hydroxynonenal (4-HNE) for oxidative damage of mitochondrial proteins and complex I activity for mitochondrial function. Natural polyphenolic antioxidant resveratrol was given in two schemes: "acute treatment," i.p. administration 30 min before, 30 and 60 min after induction of SE and "full treatment" when applications continued once daily for seven consecutive days (25 mg/kg each dose). The obtained results clearly document that the period of epileptogenesis studied (up to 4 weeks) in immature brain is associated with the significant enhanced production of O2.-, the increased levels of 3-NT and 4-HNE and the persisting deficiency of complex I activity. Application of resveratrol either completely prevented or significantly reduced markers both of oxidative stress and mitochondrial dysfunction. The findings suggest that targeting oxidative stress in combination with current antiepileptic therapies may provide a benefit in the treatment of epilepsy.

• Klíčová slova
• Epileptogenesis, Immature rats, Mitochondrial dysfunction, Oxidative stress, Protection, Resveratrol, Status epilepticus,
• MeSH
• analýza přežití MeSH
• biologické markery metabolismus   MeSH
• chování zvířat účinky léků   MeSH
• mitochondrie účinky léků   metabolismus   patologie   MeSH
• mozek patologie   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• respirační komplex I metabolismus   MeSH
• resveratrol farmakologie   MeSH
• status epilepticus patologie   MeSH
• superoxidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• respirační komplex I MeSH
• resveratrol MeSH
• superoxidy MeSH

OBJECTIVE: The pathophysiological processes leading to epileptogenesis and pharmacoresistance in epilepsy have been the subject of extensive preclinical and clinical research. The main impact on clinical practice is the development of new targeted therapies for epilepsy. We studied the importance of neuroinflammation in the development of epileptogenesis and pharmacoresistance in childhood epilepsy patients. METHODS: A cross-sectional study conducted at two epilepsy centers in the Czech Republic compared 22 pharmacoresistant patients and 4 pharmacodependent patients to 9 controls. We analyzed the ProcartaPlex™ 9-Plex immunoassay panel consisting of interleukin (IL)-6, IL-8, IL-10, IL-18, CXCL10/IP-10, monocyte chemoattractant protein 1 (CCL2/MCP-1), B lymphocyte chemoattractant (BLC), tumor necrosis factor-alpha (TNF-α), and chemokine (C-X3-X motif) ligand 1 (fractalkine/CXC3CL1) to determine their alterations in cerebrospinal fluid (CSF) and blood plasma, concurrently. RESULTS: The analysis of 21 paired CSF and plasma samples in pharmacoresistant patients compared to controls revealed a significant elevation of CCL2/MCP-1 in CSF (p < 0.000512) and plasma (p < 0.00.017). Higher levels of fractalkine/CXC3CL1 were revealed in the plasma of pharmacoresistant patients than in controls (p < 0.0704), and we determined an upward trend in CSF IL-8 levels (p < 0.08). No significant differences in CSF and plasma levels were detected between pharmacodependent patients and controls. CONCLUSION: Elevated CCL2/MCP-1 in CSF and plasma, elevated levels of fractalkine/CXC3CL1 in CSF, and a trend toward elevated IL-8 in the CSF of patients with pharmacoresistant epilepsy indicate these cytokines as potential biomarkers of epileptogenesis and pharmacoresistance. CCL2/MCP-1was detected in blood plasma; this assessment may be easily achieved in clinical practice without the invasiveness of a spinal tap. However, due to the complexity of neuroinflammation in epilepsy, further studies are warranted to confirm our findings.

• Klíčová slova
• Chemokine, Cytokine, Epileptogenesis, Interleukin, Pharmacodependent, Pharmacoresistant,
• MeSH
• biologické markery mozkomíšní mok   MeSH
• chemokin CCL2 * mozkomíšní mok   MeSH
• chemokin CX3CL1 MeSH
• epilepsie * diagnóza   farmakoterapie   MeSH
• interleukin-8 mozkomíšní mok   MeSH
• lidé MeSH
• neurozánětlivé nemoci MeSH
• průřezové studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• CCL2 protein, human MeSH Prohlížeč
• chemokin CCL2 * MeSH
• chemokin CX3CL1 MeSH
• interleukin-8 MeSH

The incidence of epilepsy is at its highest in childhood and seizures can persist for a lifetime. As brain tissue from pediatric patients with epilepsy is rarely available, the analysis of molecular and cellular changes during epileptogenesis, which could serve as targets for treatment approaches, has to rely largely on the analysis of tissue from animal models. However, these data have to be analyzed in the context of the developmental stage when the insult occurs. Here we review the current status of the available animal models, the molecular analysis done in these models, as well as treatment attempts to prevent epileptogenesis in the immature brain. Considering that epilepsy is one of the major childhood neurological diseases, it is remarkable how little is known on epileptogenesis in the immature brain at a molecular level. It is a true challenge for the future to expand the armamentarium of clinically relevant animal models, and systematic analysis of molecular and cellular data to enhance the probability of developing syndrome specific antiepileptogenic treatments and biomarkers for acquired pediatric epileptogenesis.

• MeSH
• dítě MeSH
• epilepsie epidemiologie   etiologie   patofyziologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• mozek růst a vývoj   patofyziologie   MeSH
• prevalence MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• elektrická stimulace MeSH
• elektroencefalografie MeSH
• evokované potenciály fyziologie   MeSH
• hipokampus patofyziologie   MeSH
• kojenec MeSH
• křeče u dětí patofyziologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mozek patofyziologie   MeSH
• mozková kůra patofyziologie   MeSH
• nervový přenos fyziologie   MeSH
• neurotransmiterové látky fyziologie   MeSH
• zvířata MeSH
• Check Tag
• kojenec MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• neurotransmiterové látky MeSH

• MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• epilepsie etiologie   patofyziologie   MeSH
• lidé MeSH
• mozek patofyziologie   MeSH
• psychotické poruchy etiologie   patofyziologie   MeSH
• spánek fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The authors describe the clinical and electroencephalographic findings in 220 children with focal and secondary generalized epilepsies without gross structural aetiology, with the aim of evaluating the significance of hemispheric motor prevalence for the formation, activity and possibility of compensation of the focus. Focal epileptogenesis was observed significantly more often: a) in partial seizures with elementary symptomatology in the motor non-dominant hemisphere, b) in the motor non-dominant hemisphere in boys, c) in the whole series, irrespective of the form of epilepsy and sex, in the motor nondominant hemisphere in children under the age of six and in the motor dominant hemisphere in children over the age of six. The findings in partial seizures with an elementary motor symptomatology probably arise from the very close relationship to motor areas of the cerebral cortex, in boys from evidently greater hemispheric functional asymmetry than in girls and the age correlation from unequal maturation of functionally identical parts of the brain hemispheres during ontogenesis.

• MeSH
• dítě MeSH
• dominance mozková * MeSH
• elektroencefalografie MeSH
• epilepsie parciální etiologie   MeSH
• lidé MeSH
• motorické korové centrum patofyziologie   MeSH
• předškolní dítě MeSH
• sexuální faktory MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Excitatory synapses were studied in the dentate gyrus ipsilateral to stimulated entorhinal cortex in fully kindled rats 2 weeks after the last (3rd) stage 5 seizure. In previous studies of the same model marked redistribution of synaptic vesicles to a 'strategic position' in the vicinity of the synaptic cleft and a significant enlargement of postsynaptic element were described. In this study the size and shape of synaptic vesicles were evaluated in three zones parallel to the presynaptic membrane of the synaptic cleft. The first zone (0.1 micron) directly adjoined the active zone of presynaptic membrane, the second was from 0.1 to 0.2 micron and the third from 0.2 to 0.3 micron from the presynaptic membrane. The vesicles of both the experimental and control animals were significantly smaller in zone I than in zone II and III and, in the control animals there was a tendency of vesicles to diminish towards the active zone. Such a tendency was not observed in the experimental animals, the largest vesicles were in the middle of zone II and were significantly more rounded in comparison to the vesicles in the controls. On the contrary, the vesicles in zone I and III were more elongated in the experimental animals than in controls. Our results may be taken as a sign of active reconstruction of synaptic apparatus in relation to increased functional readiness of the synapses. Possible mechanisms as well as significance for the kindling and epileptogenesis are discussed.

• MeSH
• elektronová mikroskopie MeSH
• epilepsie patologie   MeSH
• kindling * MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• synaptické vezikuly ultrastruktura   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

It remains under dispute whether status epilepticus (SE) in the perinatal period or early childhood or the underlying neuropathology is the cause of functional impairment later in life. The present study examined whether SE induced by LiCl-pilocarpine in normal immature brain (at the age of 12 or 25 days; P12 or P25) causes cognitive decline and epileptogenesis, and the data were compared to those of rats undergoing SE as adults. Rats in the P12 group had impaired memory (repeated exposure to open-field paradigm) and emotional behaviour (lower proportion of open-arm entries and higher incidence of risk assessment period in elevated plus-maze) when assessed 3 months after SE, although not as severe as in the older age groups. Importantly, video-electroencephalography monitoring 3 months after SE demonstrated that 25% of rats in the P12 and 50% in P25 group developed spontaneous seizures. Only nonconvulsive seizures (ictal activity in hippocampus accompanied by automatisms) were recorded in the P12 group whereas rats in the P25 group exhibited clonic convulsions. The present findings indicate that SE is harmful to the immature brain as early as P12, which might be compared with early infancy in humans.

• MeSH
• bludiště - učení fyziologie   MeSH
• chování zvířat fyziologie   MeSH
• elektroencefalografie MeSH
• kognitivní poruchy etiologie   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• mozek patofyziologie   MeSH
• pilokarpin toxicita   MeSH
• pohybová aktivita fyziologie   MeSH
• potkani Wistar MeSH
• status epilepticus chemicky indukované   komplikace   MeSH
• tělesná hmotnost fyziologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• pilokarpin MeSH

• MeSH
• epilepsie patofyziologie   MeSH
• lidé MeSH
• mozek patofyziologie   MeSH
• novorozená zvířata fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Temporal lobe epilepsy (TLE) is the most common epilepsy type. TLE onset in infancy aggravates features like severity, drug responsiveness, or development of comorbidities. These aggravations may arise from altered micro RNA (miRNA) expression specific to the early onset of the disease. Although the miRNA involvement in TLE is widely studied, the relationship between the onset-age and miRNA expression has not been addressed. Here, we investigated the miRNA profile of infantile and adult-onset TLE in rats combining sequencing and PCR. Since miRNA expression changes with the disease progression, we scrutinized miRNA dynamics across three stages: acute, latent, and chronic. We report that infantile-onset TLE leads to changes in the expression of fewer miRNAs across these stages. Interestingly, the miRNA profile in the acute stage of infantile-onset TLE overlaps in dysregulation of miR-132-5p, -205, and -211-3p with the chronic stage of the disease starting in adulthood. The analysis of putative targets linked the majority of dysregulated miRNAs with pathways involved in epilepsy. Our profiling uncovered miRNA expression characteristic for infantile and adulthood-onset epileptogenesis, suggesting the distinct biology underlying TLE in the onset age-dependent matter. Our results indicate the necessity of addressing the onset age as an important parameter in future epilepsy research.

• MeSH
• biologické modely MeSH
• dospělí MeSH
• epilepsie temporálního laloku etiologie   metabolismus   MeSH
• hipokampus metabolismus   MeSH
• kojenec MeSH
• krysa rodu Rattus MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• mikro RNA metabolismus   MeSH
• potkani Wistar MeSH
• regulace genové exprese MeSH
• status epilepticus metabolismus   MeSH
• transkriptom MeSH
• věk při počátku nemoci MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA MeSH