Disruption of inhibition in area CA1 of the hippocampus in a rat model of temporal lobe epilepsy.

Previous studies have revealed a loss of neurons in layer III of the entorhinal cortex (EC) in patients with temporal lobe epilepsy. These neurons project to the hippocampus and may activate inhibitory interneurons, so that their loss could disrupt inhibitory function in the hippocampus. The present study evaluates this hypothesis in a rat model in which layer III neurons were selectively destroyed by focal injections of the indirect excitotoxin, aminooxyacetic acid (AOAA).

Alcohol exposure during the brain growth spurt promotes hippocampal seizures, rapid kindling, and spreading depression.

Background: Epilepsy is a prominent sign of brain dysfunction and a cause of substantial disability in some children with fetal alcohol syndrome. The hippocampal formation is vulnerable to alcohol-induced pathologic changes and is the source of seizure activity in a variety of epileptic conditions. This study tests the hypothesis that developmental alcohol exposure facilitates epileptic activity and promotes kindling within hippocampal circuitry.

Reduced seizure threshold and hippocampal cell loss in rats exposed to alcohol during the brain growth spurt.

Background: Epilepsy is a prominent sign of neurologic dysfunction in some children with fetal alcohol syndrome (FAS). However, it is unknown whether the epileptic disorders in these children are directly due to the neuroteratogenic effects of alcohol or to some other factor accompanying maternal alcoholism. The hippocampus is vulnerable to alcohol-induced pathologic changes, and dysfunction of the hippocampus often manifests as epilepsy.

Responses of deep entorhinal cortex are epileptiform in an electrogenic rat model of chronic temporal lobe epilepsy.

We investigated whether entorhinal cortex (EC) layer IV neurons are hyperexcitable in the post-selfsustaining limbic status epilepticus (post-SSLSE) animal model of temporal lobe epilepsy. We studied naive rats (n = 44), epileptic rats that had experienced SSLSE resulting in spontaneous seizures (n = 45), and electrode controls (n = 7). There were no differences between electrode control and naive groups, which were pooled into a single control group.

Interneurons in area CA1 stratum radiatum and stratum oriens remain functionally connected to excitatory synaptic input in chronically epileptic animals.

Past work has demonstrated a reduction of stimulus-evoked inhibitory input to hippocampal CA1 pyramidal cells in chronic models of temporal lobe epilepsy (TLE). It has been postulated that this reduction in inhibition results from impaired excitation of inhibitory interneurons. In this report, we evaluate the connectivity of area CA1 interneurons to their excitatory afferents in hippocampal-parahippocampal slices obtained from a rat model of chronic TLE.

Early induction of mRNA for calbindin-D28k and BDNF but not NT-3 in rat hippocampus after kainic acid treatment.

The influence of kainic acid (KA), which induces acute seizures, on expression of mRNA for the calcium-binding protein, calbindin-D28k, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and early-response genes [c-fos, zif268 (NGFI-A), nur77 (NGFI-B)] was examined in rat hippocampus by Northern blot analysis. A significant increase (3.2-fold) in BDNF mRNA was observed 1 h after KA injection (12 mg/kg i.

Histological and 1H magnetic resonance spectroscopic imaging analysis of quinolinic acid-induced damage to the rat striatum.

NAA has been described as a neuron-specific compound. NAA levels as determined by magnetic resonance spectroscopic imaging (MRSI) have been used to determine degree of neuronal loss in several neurological diseases, but there has been limited work to document the accuracy and reliability of this technique. This study addresses this question quantitatively with histological analysis of cell viability and tissue shrinkage in quinolinic acid (QA)-induced damage of the rat striatum compared with 1H MRSI measurement of N-acetyl aspartate (NAA) as a noninvasive measure of neuronal loss.

Functional changes in somatostatin and neuropeptide Y containing neurons in the rat hippocampus in chronic models of limbic seizures.

Using immunocytochemistry and in situ hybridization analysis of mRNA, we investigated the changes in the expression of somatostatin and neuropeptide Y (NPY) in the rat hippocampal principal neurons in kindling or after electrically induced status epilepticus (SE), two models of limbic epilepsy associated with different chronic sequelae of seizures and seizure-related neuropathology. At the preconvulsive stage 2 of kindling and after three consecutive tonic-clonic seizures (stage 5) but not after a single-discharge (AD), somatostatin and NPY immunoreactivity (IR) were markedly increased in interneurons of the deep hilus and the polymorphic cell layer and their presumed projections to the outer molecular layer of the dentate gyrus. Increased mRNA levels were observed in the same neurons.

Responses of the superficial entorhinal cortex in vitro in slices from naive and chronically epileptic rats.

1. The main purposes of this study are to characterize the intracellular and extracellular responses of cells in superficial layers of entorhinal cortex (EC) in chronically epileptic animals, determine whether their altered physiology is dependent on being connected to hippocampus, and investigate whether there is evidence of augmented excitation and inhibitory interneuron disconnection. 2.

Profound disturbances of pre- and postsynaptic GABAB-receptor-mediated processes in region CA1 in a chronic model of temporal lobe epilepsy.

1. This report examines alterations in presynaptic and postsynaptic processes mediated by gamma-aminobutyric acid-B (GABAB) receptors within hippocampal region CA1 in a model of chronic temporal lobe epilepsy (TLE). Intracellular recordings were obtained in pyramidal cells from combined hippocampal/parahippocampal control slices and slices obtained > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation.

During afterdischarges in the young rat in vivo extracellular potassium is not elevated above adult levels.

Studies have suggested that in the immature brain an unusually high ceiling level for potassium may lead to an increased propensity for seizures. In these experiments, the peak levels of extracellular potassium in the hippocampus in vivo were recorded in immature rats 10-27 days old and compared to levels reached in adults. There was no difference in the peak level of potassium attained during an afterdischarge in any of the age groups tested.

Basic mechanisms of seizure expression.

While there are many types of seizures, our understanding of their pathophysiology is limited to a few types. On the basis of the behavior of neurons during a seizure, two fundamental types of paroxysms are recognized--spike-wave electrographic seizures and tonic-clonic electrographic seizures. When the former type of paroxysm takes place throughout the forebrain, an absence seizure ensues.

Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy.

Somatostatin-, neuropeptide Y-, neurokinin B- and cholecystokinin-containing neurons were investigated in the rat hippocampus in two chronic models of temporal lobe epilepsy, i.e. 30 days after rapid kindling or electrically induced status epilepticus (post-status epilepticus).

Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy.

We recently described a pronounced neuronal loss in layer III of the entorhinal cortex (EC) in patients with intractable temporal lobe epilepsy (Du et al., 1993a). To explore the pathophysiology underlying this distinct neuropathology, we examined the EC in three established rat models of epilepsy using Nissl staining and parvalbumin immunohistochemistry.

Changes in excitatory neurotransmission in the CA1 region and dentate gyrus in a chronic model of temporal lobe epilepsy.

1. In this report we compare changes of excitatory neurotransmission within the CA1 region and the dentate gyrus (DG) in a model of chronic temporal lobe epilepsy (TLE). Extracellular and intracellular recordings were obtained from in vitro hippocampal-parahippocampal slices > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation.

Changes in inhibitory neurotransmission in the CA1 region and dentate gyrus in a chronic model of temporal lobe epilepsy.

1. In this report we compare changes in inhibitory neurotransmission within the CA1 region and the dentate gyrus (DG) in a model of chronic temporal lobe epilepsy (TLE). Extracellular and intracellular recordings were obtained in combined hippocampal-parahippocampal slices > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation.

Regional heterogeneity of pathophysiological alterations in CA1 and dentate gyrus in a chronic model of temporal lobe epilepsy.

1. Extracellular and intracellular recording techniques were employed in brain slice preparations to characterize responses of hippocampal tissue in the post-self sustaining limbic status epilepticus (post-SSLSE) model of chronic temporal lobe epilepsy (TLE) as compared with responses in slices from control animals. Experiments were performed > or = 1 mo, and up to 7 mo, after status epilepticus.

Pathophysiology of status epilepticus.

The cellular and molecular pathophysiology of status epilepticus (SE) provides a conceptual framework for understanding clinical scenarios and prospectively designing logical therapies. SE is a dynamic process that evolves over time in a predictable manner with an established sequence of EEG, motor, physiologic, and cellular changes. Neuronal injury and death are the result of processes intrinsic to the brain, mediated by a complex neurotoxic cascade consisting of multiple serial and parallel processes.

Kappa opioid receptor-mediated suppression of voltage-activated potassium current in a catecholaminergic neuronal cell line.

Opioid sensitivity of a catecholaminergic cell line (CATH.a) of brainstem origin was examined using whole-cell voltage-clamp techniques. Morphine produced a preferential and concentration-dependent decrease of the amplitude of voltage-activated potassium current, IK (ED50 = approximately 4 microM, maximum inhibition 52%, n = 33).

Opioid peptide expression in models of chronic temporal lobe epilepsy.

Expression of the opioid peptides dynorphin and enkephalin is altered within the first 24 h after acutely induced seizures in certain experimental models of epilepsy. Using in situ hybridization, we examined the expression of prodynorphin and preproenkephalin messenger RNA acutely following induction of kindling with recurrent seizures and in two models of chronic temporal lobe epilepsy: (i) rats fully kindled with rapidly recurring hippocampal seizures; and (ii) rats surviving after self-sustaining limbic status epilepticus induced with focal electrical stimulation of the hippocampus. In naive animals, a ventral-dorsal gradient was identified in the expression of both prodynorphin and preproenkephalin messenger RNA in the dentate gyrus and expression of prodynorphin message was demonstrated for the first time in the ventral portion of cornu Ammonis regio superior.

The role of extracellular ionic changes in upregulating the mRNA for glial fibrillary acidic protein following spreading depression.

While spreading depression has been shown to be a powerful stimulus in upregulating glial fibrillary acidic protein (GFAP) mRNA expression, the specific physiological signal underlying the upregulation is unknown. During spreading depression, extracellular ionic concentrations are altered markedly. The present study evaluates the role of these changes in extracellular ionic concentrations as potential signals influencing GFAP mRNA expression.

Voltage-activated potassium currents in acutely dissociated hippocampal dentate gyrus neurons from neonatal rats.

We have studied outward currents of neurons acutely dissociated from the dentate gyrus region of hippocampus using whole-cell and perforated patch recordings. Depolarizing voltage commands activated sustained outward currents at all age tested (P5-P30). Outward currents were blocked by tetraethylammonium (10 mM) but not 4-aminopyridine (25 mM).