Threshold intensities for epileptic phenomena induced by cortical stimulation were used for comparison of the action of GABA-B and GABA-A antagonists in rats with implanted electrodes. Both CGP 35348 (200 mg/kg i.p.) and bicuculline (4 mg/kg i.p.) significantly decreased thresholds for spike-and-wave afterdischarges and their motor counterpart (clonic seizures) whilst transition into the second, limbic type of afterdischarge as well as threshold for movements directly bound to stimulation remained uninfluenced by either drug., D. Živanović, K. Bernášková, Yu. Kaminskij, P. Mareš., and Obsahuje bibliografii
The effects of phenytoin on threshold intensities of stimulation were studied in cortical epileptic afterdischarges (ADs) in 12-day-old and adult rats with implanted electrodes. Stimulation of the sensorimotor cortical area induced movements directly related to the stimulation as well as EEG afterdischarges (ADs) of the spike-and-wave type and of the limbic type. Rat pups exhibited lower thresholds for stimulation-bound movements and spike-and- wave ADs than adult animals. On the contrary, the limbic type of ADs was elicited with lower current intensity in adult than in immature rats. Phenytoin increased the threshold for stimulation-related movements only in adult rats, whereas threshold intensities for spike-and-wave ADs were increased and thresholds for limbic type of ADs remained uninfluenced in both age groups. The age-dependent effect on stimulation-related movements might be due to a maturation of connectivity in the motor system or to developmental changes in the voltage-gated sodium channels as the main target of phenytoin action.
Cortical epileptic foci elicited by local application of bicuculline methiodide represent a model of interictal epileptic activity with a transition into ictal phases. We studied a role of GABA-B receptors in this model using GABA-B receptor antagonist CGP35348 in adult rats with implanted cortical electrodes and cannula. CGP35348 (100 or 200 mg/kg i.p.) did not affect interictal discharges but it augmented ictal activity. Latency to the first ictal episode was decreased by the lower dose of CGP35348, duration of episodes was increased by the higher dose. GABA-B receptor antagonist did not influence purely cortical epileptic phenomenon but it is proconvulsant in ictal activity generated with participation of subcortical structures., P. Mareš, K Bernášková, H. Kubová., and Obsahuje seznam literatury
Seizures were induced in 7-day-old rats by intraperitoneal injection of DL-homocysteine thiolactone. Phosphocreatine (PCr), ATP, glucose, glycogen and lactate were determined in the cerebral cortex during various intervals after injection, corresponding to the early, as well as long periods of seizure activity. The unchanged levels of ATP, a very mild PCr decline and a pronounced accumulation of lactate (in the face of modest changes in brain glucose and glycogen) were observed. These results suggest that the immature rat brain is able to compensate energy expenditure associated with seizure activity by increased energy production, mainly due to increased anaerobic glycolysis. It remains to be determined whether a similar conclusion is also valid for other brain regions, e.g. subcortical structures.
Threshold intensities for elicitation of movements and of epileptic afterdischarges by rhythmic stimulation of the sensorimotor cortex were estimated in 90 rats with implanted electrodes. Four age groups were studied - animals 12, 18, 25 and 90 days old. Both thresholds exhibited significantly higher values for adult animals in comparison with all groups of young pups. Whereas no differences were found among the rat pups in thresholds for movements accompanying stimulation, epileptic afterdischarges demonstrated a lower threshold in 18-day- old in comparison with 25-day-old animals. The development of cortical excitability is rather complicated and deserves further studies.
The action of phenytoin was studied in acute experiments in rats with brainstem transection at the midcollicular level. Symmetrical epileptogenic foci were elicited in sensorimotor cortical areas of both hemispheres by local application of penicillin. Seven rats formed a control group, ten animals were pretreated with phenytoin (60 mg/kg i.p., 10 min before penicillin application). Synchronization of interictal discharges in control rats was delayed in comparison to animals with an intact brainstem; phenytoin did not influence this synchronization. Spontaneous transition of interictal into ictal activity was not abolished by phenytoin, i.e. in cerveau isolé preparations phenytoin lost this activity. The loss of anticonvulsant activity was not complete. Ictal episodes were modified; they started as very short ones and their duration progressively increased. Structures localized below the level of transection represent a site of at least one of the mechanisms of phenytoin anticonvulsant action.
The extent of ADP.Fe/NADPH-induced lipid peroxidation measured as production of thiobarbituric acid-reactive substances (TBARS) was determined in isolated membranes from cerebral cortex, heart and kidney of 21-days- old rats. The time course of lipid peroxidation showed higher production of TBARS in cerebral cortex than in heart and kidney. Our data indicate that high level of TBARS production is not due to high activity of NADPH oxidoreductase but due to high content of endogenous lipids in cerebral cortex membranes that could be modified. Higher production of TBARS in cerebral cortex is the result of higher content of lipids in cerebral cortex membranes because NADPH cytochrome c reductase activity in membranes of cerebral cortex is lower than that of heart and kidney.
In the developing brain, mature brain derived neurotrophic factor (mBDNF) and its precursor (proBDNF) exhibit prosurvival and proapoptotic functions, respectively. However, it is still unknown whether mBDNF or proBDNF is a major form of neurotrophin expressed in the immature brain, as well as if the level of active caspase -3 correlates with the levels of BDNF forms during normal brain development. Here we found that both proBDNF and mBDNF were expressed abundantly in the rat brainstem, hippocampus and cerebellum between embryonic day 20 and postnatal day 8. The levels of mature neurotrophin as well as mBDNF to proBDNF ratios negatively correlated with the expression of active caspase -3 across brain regions. The immature cortex was the only structure, in which proBDNF was the major product of bdnf gene, especially in the cortical layers 2-3. And only in the cortex, the expression of BDNF precursor positive ly correlated with the levels of active caspase -3. These findings suggest that proBDNF alone may play an important role in the regulation of naturally occurring cell death during cortical development., P. N. Menshanov, D. A. Lanshakov, N. N. Dygalo., and Obsahuje bibliografii
Action of antiepileptic drugs in immature brain may differ from that in adult brain. The aim of our study was to study an anticonvulsant action of lamotrigine and phenytoin, i.e. two drugs active against partial seizures in adult experimental animals as well as human patients, in a model of simple partial seizures in immature rats. Epileptic foci were induced by local application of bicuculline methiodide on sensorimotor cortical area of 12-dayold rat pups. The animals were pretreated with lamotrigine (LTG, 10 or 20 mg/kg i.p.) or phenytoin (PHT, 15, 30 or 60 mg/kg i.p.). Control rats for LTG received saline, controls for PHT solvent composed of propyleneglycol, ethanol and water. Influence of either drug on interictal activity was negligible. High doses of both LTG and PHT suppressed the transition into ictal phases and shortened the duration of persisting seizures. The tricomponent solvent exhibited moderate activity against ictal activity if compared with saline controls. The two drugs exhibited similar action in our model, i.e. the suppression of secondary generalization from epileptic focus. This action is comparable to that described for human patients and adult experimental animals. In favor of lamotrigine speaks the absence of serious side effects., K. Bernášková, P. Mareš., and Obsahuje bibliografii a bibliografické odkazy
Repeated postnatal caffeine treatment of rat pups led to transient developmental changes in cortical epileptic afterdischarges. To know if physiological cortical functions are also affected transcallosal evoked potentials were studied. Rat pups of the Wistar strain were injected daily with caffeine (10 or 20 mg/kg s.c.) from postnatal day (P) 7 to P11, control siblings received saline. Cortical interhemispheric responses were tested at P12, 18, 25 and in young adult rats. Amplitude of initial monosynaptic components was evaluated in averaged responses. Single pulses as well as paired and frequency (five pulses) stimulations were used. Developmental rules - highest amplitude of responses in 25-day-old rats, potentiation with paired and frequency stimulation present since P18 - were confirmed. Caffeine-treated rats exhibited transient changes: single responses were augmented in P25 if high stimulation intensity was used, paired-pulse and freque ncy responses were higher in experimental than in control anim als at P12, the opposite change was observed in 18- and more ma rkedly in 25-day-old rats. No significant changes were found in adult animals, monosynaptic transcallosal responses represent a simple and robust system. The developmental profile of described changes did not exactly correspond to changes in epileptic afterdischarges supporting the possibility that afterdischarges did not arise from early monosynaptic components of responses. In spite of transient nature of changes they can reflect delayed or more probably modified brain development., J. Tchekalarova, H. Kubová, P. Mareš., and Obsahuje bibliografii a bibliografické odkazy