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T L Babb

Publications and source records attributed to T L Babb.

116 records · Page 7Linked to original sources
PubMedDate not supplied

Inhibition in synchronously firing human hippocampal neurons.

In order to study the extent of inhibition in human epileptic hippocampus, we recorded extracellular unit activities of human hippocampal neurons and their responses to single pulse stimulation in temporal lobe epilepsy patients during interictal periods. The criteria for diagnosing the hippocampus as epileptic were: (1) all seizures originated in that one hippocampus, (2) surgical removal of that hippocampus resulted in seizure relief, and (3) the surgically excised hippocampus was sclerotic. Analysis of firing pattern by cross-correlation showed that synchronized firing between neurons occurred only in the epileptic hippocampus. However, synchronized firing was not limited to only bursting neurons, as previously reported in some animal models of epilepsy, but was also observed among non-bursting neurons in the epileptic hippocampus. Furthermore, no significant difference in distribution of burst-discharge neurons was found between epileptic and non-epileptic hippocampi. In response to single pulse stimulation, neurons in both 'normal' (contralateral hippocampus) and epileptic hippocampus showed a rapid increase of firing (excitation), cessation of firing (inhibition), or a sequence of both (initial excitation followed by inhibition). However, a significant difference was found in the duration of the inhibition between synchronously firing neurons and non-synchronously firing neurons: the inhibition evoked by a single stimulation in synchronously firing epileptic neurons was significantly longer (373.8 msec +/- 35.9 S.E.M., P less than 0.005) than that of non-synchronously firing neurons (83.9 msec +/- 8.9 S.E.M.). Moreover, prolonged inhibition in synchronously firing epileptic neurons could occur with little or no prior excitation, suggesting that this inhibition does not necessarily depend on an intrinsic Ca2+-dependent K+-mediated after-burst hyperpolarization but is rather likely to be synaptic. As this inhibition was longer when epileptic neurons fired in synchrony, it could be interpreted that principal neurons recruited more recurrent inhibitory circuits by firing synchronously. By taking into account the previously reported neurophysiological evidence in human in vitro epileptic tissue showing GABA-mediated inhibition and the neuroanatomical evidence in excised human epileptic hippocampus showing GAD-positive neurons and synapses, our data suggest that, in human chronic epileptic hippocampus, recurrent inhibition remains functional, and alterations in GABA-mediated inhibition may not represent the critical change responsible for seizure generation.

Action Potentials↗
PubMedDate not supplied

Recovery of decreased glutamate decarboxylase immunoreactivity after rat hippocampal kindling.

The present study was designed to test the hypothesis that chronic gamma-aminobutyric acid (GABA) disinhibition of granule cells could explain permanent kindled epileptogenicity. Quantitative and statistical comparisons of glutamate decarboxylase immunoreactivity (GAD-IR), the synthesizing enzyme for GABA, were made of GAD-IR cells and puncta in stratum granulosum of the fascia dentata. The use of GAD immunocytochemistry in kindled and control tissue was used to allow direct anatomic confirmation that we were measuring changes in GAD-IR which would represent GABA synthesis for release by the recurrent inhibitory system of the fascia dentata. Immediately after the last kindled seizure, optically detected GAD-IR puncta densities were significantly reduced in stratum granulosum. At 3 or 7 days after the last kindled seizure, GAD-IR was normal in puncta, indicating that the transient GAD-IR loss was probably a metabolic response to the recent seizure represented by over-use of GAD needed for synthesis of GABA after a prolonged kindled seizure. When the prolonged kindled seizures were discontinued GAD-IR recovered in the puncta. This transient effect did not occur in other areas such as Ammon's horn (CA3) or substantia nigra. The extent of the GAD-IR loss showed no correlation with the severity of the final behavioral seizure (R = 0.23), or the final afterdischarge (AD) duration in entorhinal cortex (R = 0.17) or motor cortex (R = 0.53). A massed stimulation control group given 19 shorter-duration ADs every 10 min (non-kindling) did not reduce GAD-IR. These findings support the hypothetical model that prolonged kindled seizures release excessive GABA which depletes GAD in axon terminals for 1 day after the seizure. However, such a transient suppression of GAD-IR provides no evidence that disinhibition contributes to the kindling process, because kindling proceeds normally with inter-seizure intervals as long as 1 week. The finding of full recovery of GAD-IR within 1 week does not support the model of loss of GABA inhibition to explain the permanency of kindled epileptogenesis.

Animals↗
PubMedDate not supplied

GABAergic neurons are spared after intrahippocampal kainate in the rat.

The present study used Nissl stains and glutamate decarboxylase immunoreactivity (GAD-IR) to quantify the acute and chronic toxicity of kainic acid (KA) on focal and remote hippocampal principal neurons (i.e., pyramidal and granule cells) and on putative inhibitory neurons (GAD-IR or GABAergic) following intrahippocampal KA administration. Concentrations of 0.5, 1.0, 1.25 or 1.5 micrograms KA/0.2 microliters were injected unilaterally into the posterior hippocampus of rats (n = 32), with survival periods of 1, 3, 5, 14, 21, 30 and 60 days. The age-matched control animals (n = 10) received an intrahippocampal injection of 0.2 microliter saline (sham control, n = 4) or no injection (normal, n = 6). The ipsilateral (KA+) cell counts demonstrated a selective vulnerability of CA3 and CA4 pyramidal neurons which was maximal at 14 days and unchanged to 60 days. However, in the same region, putative inhibitory (GAD-IR) neurons were resistant to the neurotoxic effects of KA. Contralateral (KA-) pyramidal cell and GAD-IR neuron densities were equivalent to controls. The present data demonstrate a selective resistance to KA by GABA neurons compared to the vulnerability of pyramidal neurons. Because GABA neurons are relatively spared in the KA focus, loss of GABAergic inhibitory neurons is probably not a mechanism for the seizure sensitivity in the KA model.

Animals↗
PubMedDate not supplied

Interhemispheric propagation time of human hippocampal seizures. I. Relationship to surgical outcome.

This study evaluated ictal stereotaxic electroencephalogram (SEEG) records in 75 patients with complex partial seizures who later received anterior temporal lobectomy and were evaluated for long-term seizure relief. The time required for seizures to propagate from the putatively epileptogenic hippocampal formation to the contralateral hippocampal formation was measured from 615 ictal SEEG records. These interhemispheric propagation times were then compared with the degree of post-lobectomy seizure relief. Poor postsurgical seizure relief was associated with seizure propagation times of less than or equal to 5 s. Relief or reduction of seizures after surgery was associated with seizure propagation times greater than 50 s. These relationships were also found to occur in a subset of 56 patients who did not exhibit interhemispheric propagation times of less than 0.5 s, thus indicating that interhemispheric propagation times in the range of 0.5-5 s is a negative prognostic sign even in the absence of "bilaterally synchronous" ictal SEEG onsets. The finding of longer interhemispheric propagation times in patients who were improved by surgery may be accounted for by the greatly reduced size, or absence, of the hippocampal commissure in humans and suggests that the corpus callosum is a major, albeit indirect, route by which hippocampal foci may propagate seizure activity contralaterally. The finding of shorter interhemispheric propagation times in patients who did poorly after surgery may be accounted for by the existence of foci outside the region of excision with more direct access to callosal pathways or, alternatively, by the presence of damage in a more seizure-prone contralateral hippocampus.

Electroencephalography↗
PubMedDate not supplied

Interhemispheric propagation time of human hippocampal seizures: II. Relationship to pathology and cell density.

The time required for hippocampal seizure activity to propagate to the contralateral hippocampal formation was evaluated in 57 patients with complex partial seizures and related to histological findings following temporal lobectomy. Interhemispheric propagation times were found to be significantly longer (greater than 20 s) in those patients diagnosed as having hippocampal sclerosis than in those patients without hippocampal sclerosis. Quantitative analysis of cell densities was made in 28 patients. Dentate fascia granule densities and hippocampal pyramidal cell densities were found to be lower in those patients with longer interhemispheric propagation times. However, this relationship was not observed when only patients with hippocampal sclerosis were considered. Thus, a tendency for hippocampal seizures to exhibit interhemispheric propagation times greater than 20 s is suggestive of underlying hippocampal sclerosis. However, information about interhemispheric propagation time does not appear useful for estimating the actual degree of cell loss within the sclerotic hippocampus. The association of longer interhemispheric propagation times with hippocampal sclerosis supports the hypothesis that direct commissural connections between the hippocampal formations in humans are either unimportant or missing.

Electroencephalography↗
PubMedDate not supplied

Quantitative comparison of cell loss and thiopental-induced EEG changes in human epileptic hippocampus.

Thiopental-induced EEG beta activity recorded from mesial and lateral temporal lobe sites was analyzed both visually and by computer in 30 patients with complex partial seizures. All patients later received anterior temporal lobectomy. Volumetric cell densities and percentage of principal cell loss relative to normal controls were determined in several different areas of each resected temporal lobe. The percentage of drug-induced beta activity was then compared with the percentage of cell loss by (a) making precise topographic correlations between induced beta and cell loss, (b) relating the overall degree of left/right beta asymmetry to cell loss averaged over wide regions, and (c) comparing the likelihood of left/right beta asymmetries in patients with and without extreme cell loss. The results obtained were consistently negative and were unaffected by whether EEG data were analyzed by computer or visual inspection. These results indicate that the well-known loss of drug-induced beta activity found in epileptogenic regions is not an indicator of the degree of cell loss or sclerosis. The underlying focal dysfunction measured by EEG beta activity remains unknown, and factors such as focal hypoperfusion, hypometabolism, and the microanatomic features of the cells remaining in the focus should be investigated.

Beta Rhythm↗
PubMedDate not supplied

Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting.

We used the pilocarpine model of chronic spontaneous recurrent seizures to evaluate the time course of supragranular dentate sprouting and to assess the relation between several changes that occur in epileptic tissue with different behavioral manifestations of this experimental model of temporal lobe epilepsy. Pilocarpine-induced status epilepticus (SE) invariably led to cell loss in the hilus of the dentate gyrus (DG) and to spontaneous recurrent seizures. Cell loss was often also noted in the DG and in hippocampal subfields CA1 and CA3. The seizures began to appear at a mean of 15 days after SE induction (silent period), recurred at variable frequencies for each animal, and lasted for as long as the animals were allowed to survive (325 days). The granule cell layer of the DG was dispersed in epileptic animals, and neo-Timm stains showed supra- and intragranular mossy fiber sprouting. Supragranular mossy fiber sprouting and dentate granule cell dispersion began to appear early after SE (as early as 4 and 9 days, respectively) and reached a plateau by 100 days. Animals with a greater degree of cell loss in hippocampal field CA3 showed later onset of chronic epilepsy (r = 0.83, p < 0.0005), suggesting that CA3 represents one of the routes for seizure spread. These results demonstrate that the pilocarpine model of chronic seizures replicates several of the features of human temporal lobe epilepsy (hippocampal cell loss, supra- and intragranular mossy fiber sprouting, dentate granule cell dispersion, spontaneous recurrent seizures) and that it may be a useful model for studying this human condition. The results also suggest that even though a certain amount of cell loss in specific areas may be essential for chronic seizures to occur, excessive cell loss may hinder epileptogenesis.

Animals↗