Changes of cortical epileptic afterdischarges after status epilepticus in immature rats

Status epilepticus (SE) in developing rats leads to neuronal degeneration in many brain structures including neocortex but the functional consequences of cortical damage were studied only exceptionally. Lithium-pilocarpine SE was elicited in 12- (P12) and 25-day-old (P25) rats, convulsions were interrupted after 2h by paraldehyde. Cortical electrodes were implanted 3, 6, 9, 13 and/or 26 days after SE. Low-frequency stimulation of sensorimotor cortex was repeated with at least 10-min intervals with a stepwise increasing intensity (0.2-14 mA). Thresholds for movements elicited by stimulation, spike-and-wave afterdischarges (ADs), clonic seizures, mixed ADs (transition into a limbic type of ADs) and recurrent ADs as well as duration of ADs were evaluated. The first three phenomena were not influenced by SE with the exception of lower thresholds for movements during stimulation. Transition into limbic seizures and recurrent seizures were delayed in both age groups and threshold intensities for limbic ADs were at some intervals higher in SE than in control animals. Duration of ADs was changed only at short intervals after SE; it was shortened at 3 and 6 days in P25 and 3 days in P12 rats, respectively. P12 group then exhibited a transient increase in duration of ADs 6 days after SE. Our results did not prove a higher cortical excitability after SE in either age group. On the contrary, there were some signs of a decreased excitability

Which component of treatment is important for changes of cortical epileptic afterdischarges after status epilepticus in immature rats?

Role of lithium chloride and paraldehyde in acute changes after lithium-pilocarpine status epilepticus (SE) induced at postnatal day 12 was studied in 15-day-old rats. In addition to SE group four other groups were formed: na\uefve animals without any injection, lithium chloride group, paraldehyde group and lithium-paraldehyde group. Cortical epileptic afterdischarges (CxADs) induced by increasing intensities of stimulation current were used as a measure of excitability. SE animals did not exhibit any change in duration of CxADs with increasing stimulation intensity in contrast to na\uefve control with a progressive prolongation of CxAD. LiCl group was similar to SE rats whereas paraldehyde and lithium-paraldehyde groups exhibited some progress in duration of ADs. Lithium chloride participates in short-term changes of CxADs after SE. Paraldehyde and combination of lithium and paraldehyde are similar to na\uefve controls

Changes of cortical interhemispheric responses after status epilepticus in immature rats

PURPOSE: To study cortical excitability after status epilepticus induced in two age groups of immature rats. METHODS: Lithium-pilocarpine status epilepticus was elicited in 12- (SE12) or 25-day-old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of sensorimotor region of cerebral cortex 3, 6, 9, 13, or 26 days after status. Single biphasic pulses with intensities from 0.2 to 4 mA were used for stimulation; eight responses were always averaged. Amplitude of the first positive and negative waves (i.e., monosynaptic transcallosal responses) was measured and used for construction of input-output (I/O) curves. FluoroJade B was used to visualize degenerating neurons 24 h after status in both age groups. RESULTS: No significant changes were found at short intervals, but only a tendency to lower amplitudes 3 days after status in SE12 group. Marked changes appeared 26 days after status. The younger group exhibited lower amplitudes than did control rats, whereas SE25 animals generated responses with higher amplitude than did controls (i.e., the I/O curve was steeper. FluoroJade B-positive neurons were scarce in SE12 rats, whereas a substantial number of positive neurons was found in SE25 animals. The positive neurons exhibited characteristics of interneurons, and their distribution in cortical layers differed in the two groups. CONCLUSIONS: Status epilepticus resulted in neuronal death in both SE12 and SE25 animals. Changes in transcallosal evoked potentials were opposite in the two age groups. Augmented amplitude of responses in SE25 rats may indicate an increased cortical excitability

Intrahippocampal injection of endothelin-1 in immature rats results in neuronal death, development of epilepsy and behavioral abnormalities later in life

The direct injection of endothelin-1 (ET-1) into brain parenchyma was recently suggested as a suitable model of stroke. The present study was designed to assess whether intrahippocampal injection of ET-1 in immature rats causes neurodegeneration and immediate seizures, and results in impairment of motor development, cognitive decline, epilepsy and chronic hippocampal lesion. ET-1 was injected unilaterally into the dorsal hippocampus in doses of 20 or 40 pmol at the age of 12 (P12) or 25 (P25) days. Video-electroencephalographic monitoring performed during 100 min after the injection of ET-1 demonstrated the development of convulsive epileptic seizures in 75-100% of animals of individual age-and-dose groups. Long-term behavioral follow-up did not reveal impairment of motor development in any dose-and-age group. At 2 months after ET-1 injection, impairment of spatial memory occurred only in rats with 40 pmol of ET-1 at P12. At 3 months after ET-1 injection spontaneous electrographic seizures occurred in 62.5-100% animals of both ages with no relation to the dose used. Seizures were always non-convulsive. The total seizure duration per 24 h was higher in the P12 than the P25 group, suggesting more severe epilepsy. The extent of the hippocampal lesion increased with the dose of ET-1 and was significantly higher in the P12 than the P25 group. The severity of the ET-1-induced lesion correlated positively with total seizure duration per 24 h at both ages. Our results document that early intrahippocampal injection of ET-1 results in lesion development and both immediate seizures and chronic epilepsy in either age group. Cognitive impairment occurred only in rats with ET-1 injection at P12

Age-dependent suppression of hippocampal epileptic afterdischarges by metabotropic glutamate receptor 5 antagonist MTEP

Action of an antagonist of metabotropic glutamate receptors subtype 5 MTEP was studied in a model of complex partial seizures. Dorsal hippocampus of rat pups 12, 18 and 25 days old was stimulated six times with 10-min intervals. MTEP (20 or 40 mg/kg) was injected after the first afterdischarge and duration of afterdischarges was measured. MTEP exhibited marked anticonvulsant action in 12-day-old-rats, the similar effect in 18-day-old rats was observed only with the second stimulation. No anticonvulsant action was seen in 25-day-old animals. Our results may qualify antagonists of mGluR5 as potential antiepileptic drugs for some types of childhood epilepsies