Biomedical subjects

E H Bertram

Publications and source records attributed to E H Bertram.

40 records · Page 3Linked to original sources

PubMed1990

The hippocampus in experimental chronic epilepsy: a morphometric analysis.

The effect of intermittent seizures on the pyramidal neurons of the hippocampus is largely unknown. To determine whether recurrent seizures centered in the hippocampus can produce neuronal loss in this region, a morphometric analysis was performed from standardized sections of hippocampus using 5 groups of animals: (1) surgical control subjects, (2) rats kindled by the rapidly recurring hippocampal seizure (RRHS) paradigm, (3) kindled rats with a few additional limbic seizures (528 +/- 66 seizures), (4) kindled rats with many limbic seizures (1,523 +/- 130 seizures), and (5) rats experiencing limbic status epilepticus (SE) induced by "continuous" hippocampal stimulation. The RRHS and SE protocols induced significant neuronal loss in the CA1 region, but no evidence was found for additional cell loss with increasing numbers of intermittent seizures. These intermittent seizures were, however, associated with a significant thickening of the basal and apical dendritic fields of the CA1 region. These findings indicate that intermittent seizures produce no significant hippocampal neuronal loss and may result in a hypertrophy of CA1 dendritic fields.

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PubMed1990

NMDA receptor antagonists and limbic status epilepticus: a comparison with standard anticonvulsants.

Status epilepticus (SE) evolves through several stages when untreated. The later stages of SE are less responsive to standard anticonvulsants and may require general anesthesia to suppress seizures. Antagonists acting at the N-methyl-D-aspartate (NMDA) subclass of glutamate (excitatory) receptors have been demonstrated to exert antiepileptic activity in some seizure models. We report experiments performed to determine if NMDA receptor antagonists are effective in stopping seizures in the late stages of SE. A model of limbic SE induced by 90 min of 'continuous' electrical stimulation of the hippocampus in rats was employed. Three NMDA receptor antagonists, one 'competitive' (CPP) and two 'non-competitive' (ketamine and MK-801), were compared to 3 standard antiepileptic drugs (diazepam, phenobarbital, and phenytoin) for their ability to suppress seizures at a physiologically defined stage of SE. All NMDA receptor antagonists, diazepam and phenobarbital were effective in suppressing behavioral and electrographic seizures for varying periods of time. Phenytoin had no effect on SE. Ketamine and MK-801 induced a paradoxical enhancement of electrographic seizures that preceded SE suppression. We believe that NMDA-receptor antagonists offer a novel approach for treating the late stages of SE.

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PubMed1990

Recurrent spontaneous hippocampal seizures in the rat as a chronic sequela to limbic status epilepticus.

A period of continuous hippocampal stimulation (CHS) establishes an acute condition of self-sustaining limbic status epilepticus (SSLSE) which is followed by chronic neuropathological changes reminiscent of hippocampal sclerosis encountered in epileptic patients. In the chronic (greater than or equal to 1 month) condition following CHS-induced SSLSE, extended electrographic monitoring in the hippocampus revealed spontaneous recurrent paroxysmal discharges. All 6 animals studied had persistent interictal spiking; 3 had multiple fully developed electrographic seizures. There was a marked diminution of paired pulse inhibition, demonstrated by a protocol known to reflect the potency of inhibition mediated by GABAA receptors. Hippocampal slices from animals that had previously experienced CHS-induced SSLSE demonstrated an increased excitability relative to slices from control animals as evidenced by epileptiform bursting in increased extracellular potassium ([K+]0) and decreased extracellular calcium ([Ca2+]0). These studies establish that CHS-induced SSLSE in rats provides an experimental model with recurrent spontaneous hippocampal seizures. Based on electrophysiological data we suggest that a decrease in GABA-mediated inhibition and/or altered sensitivity to extracellular ions may play roles in the development of such seizures.

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PubMedDate not supplied

Self-sustaining limbic status epilepticus induced by 'continuous' hippocampal stimulation: electrographic and behavioral characteristics.

A model of status epilepticus centered in the limbic system and elicited by 'continuous' focal electrical stimulation of the hippocampus is presented. Under appropriate conditions, the status epilepticus persisted for many hours after discontinuing the electrical stimulus. The critical determinant for the establishment of this self-sustaining limbic status epilepticus (SSLSE) was the length of stimulation, rather than the side (left vs. right) of stimulation or kindling before stimulation. Observations, obtained from stimulus-free intervals spaced regularly during the stimulus protocol and from the period after stimulation had been completed, revealed a distinct and stereotyped electrographic progression of SSLSE though several stages. Brief monitoring periods throughout the stimulus protocol yielded electrographic criteria that predicted which animals would experience experience SSLSE. The presence of synchronous, stimulus-independent seizure activity bilaterally in the hippocampi during stimulation was necessary to establish SSLSE. Intense motor seizure activity, like that seen with kindled motor seizures, occurred intermittently during SSLSE. However, 'limbic' behavioral seizures identical to those seen after low doses of kainic acid or during the early stages of kindling were nearly continuous. These studies indicate that there is a predictable course to limbic status epilepticus and point to the hippocampus as a key element involved in initiating and maintaining this syndrome.

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