Distribution of Pyramidal Cell Density and Hyperexcitability in the Epileptic Human Hippocampal Formation

Babb, Thomas L.; Lieb, Jeffrey P.; Brown, W. J.; Pretorius, James K.; Crandall, Paul H.

doi:10.1111/j.1528-1157.1984.tb03483.x

Cited by 247 publications

(92 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, in all rats (six of six) that developed SSSE as a result of injection of 10 pmol SP combined with 7-min PPS, severe neuronal loss, greater on the side of stimulation, occurred bilaterally throughout the CA1 and CA3 pyramidal cell layers (Fig. 3 C and G), in a distribution resembling that seen in human epilepsy (29). No detectable cell loss was found in the hippocampi of rats coinjected with spantide II and SP combined with 7-min PPS (data not shown).…”

Section: Resultsmentioning

confidence: 94%

Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus

Liu¹,

Mazarati²,

Katsumori³

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

108

View full text Add to dashboard Cite

Substance P (SP), a member of the tachykinin family, is widely distributed in the central nervous system and is involved in a variety of physiological processes including cardiovascular function, inflammatory responses, and nociception. We show here that intrahippocampal administration of SP triggers self-sustaining status epilepticus (SSSE) in response to stimulation of the perforant path for periods too brief to have any effect in control rats, and this SSSE generates a pattern of acute hippocampal damage resembling that known to occur in human epilepsy. The SP receptor (SPR) antagonists, spantide II and RP-67,580, block both the initiation of SSSE and SSSE-induced hippocampal damage and terminate established anticonvulsantresistant SSSE. SSSE results in a rapid and dramatic increase in the expression of preprotachykinin A (a precursor of SP) mRNA and SP in principal neurons in CA3, CA1, and the dentate gyrus as well as in hippocampal mossy fibers. SP also increases glutamate release from hippocampal slices. Enhanced expression of SP during SSSE may modulate hippocampal excitability and contribute to the maintenance of SSSE. Thus, SPR antagonists may constitute a novel category of drugs in antiepileptic therapy.Feed-forward excitation travels along a hippocampal trisynaptic circuit, in which dentate gyrus (DG) granule cells make excitatory synaptic connections via mossy fibers onto CA3 pyramidal neurons that, in turn, form excitatory synaptic connections onto CA1 pyramidal neurons (1, 2). This hippocampal circuit displays considerable neurochemical plasticity in response to lesions and change in afferent activity (3-6). Substance P (SP), a member of peptides belonging to the tachykinin family, is present in low concentration in the rat hippocampus (7,8). However, its expression, like that of other neuropeptides, shows considerable plasticity and can be regulated by drugs (9-11), neuronal activity (12, 13), and convulsant kainic acid (14,15). SP is well established as a neurotransmitter͞neuromodulator (16) and is released by various stimuli (17, 18). There is evidence to suggest that SP modulates neuronal membrane excitability by virtue of slow synaptic currents (19), raises intracellular Ca 2ϩ concentrations (20), and enhances responses to excitatory amino acids (21). Using a new animal model (22), we now present evidence that SP plays an important role in the severe seizures seen in selfsustaining status epilepticus (SSSE) and in modulating hippocampal excitability. MATERIALS AND METHODS Induction and Analysis of Status Epilepticus (SE).Male Wistar rats (240-280 g) were implanted under anesthesia (ketamine 60 mg kg Ϫ1 ͞xylazine 15 mg kg Ϫ1) with a bipolar stimulating electrode into the angular bundle of the perforant path and a bipolar recording electrode into the granule cell layer of the ipsilateral DG. To standardize the position of the electrode, only animals in which population spike amplitude was Ն2 mV were used. Seven days after surgery, animals were stimulated in the awake state for 30 min wit...

show abstract

Section: Resultsmentioning

confidence: 94%

Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus

Liu¹,

Mazarati²,

Katsumori³

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

108

View full text Add to dashboard Cite

show abstract

“…86 Studies with depth electrodes in the hippocampus of TLE patients show that seizure activity originates from such hippocampi, and especially from the most sclerotic regions within them. 87 How does this happen? How does the hyperexcitability of the dentate granule cells 88 spread to the subiculum, through the neuron-depleted area CA1?…”

Section: What Role Do Astrocytes Play In the Hippocampal Seizure Focus?mentioning

confidence: 99%

Astrocytes and Epilepsy

2010

View full text Add to dashboard Cite

Summary: Astrocytes form a significant constituent of seizure foci in the human brain. For a long time it was believed that astrocytes play a significant role in the causation of seizures. With the increase in our understanding of the unique biology of these cells, their precise role in seizure foci is receiving renewed attention. This article reviews the information now available on the role of astrocytes in the hippocampal seizure focus in patients with temporal lobe epilepsy with hippocampal sclerosis. Our intent is to try to integrate the available data. Astrocytes at seizure foci seem to not be a homogeneous population of cells, and in addition to typical glial fibrillary acidic protein, positive reactive astrocytes also include a population of neuron glia-2-like cells The astrocytes in sclerotic hippocampi differ from those in nonsclerotic hippocampi in their membrane physiology, having elevated Naϩ channels and reduced inwardly rectifying potassium ion channels, and some having the capacity to generate action potentials. They also have reduced glutamine synthetase and increased glutamate dehydrogenase activity. The molecular interface between the astrocyte and microvasculature is also changed. The astrocytes are also associated with increased expression of many molecules normally concerned with immune and inflammatory functions. A speculative mechanism postulates that neuron glia-2-like cells may be involved in creating a high glutamate environment, whereas the function of more typical reactive astrocytes contribute to maintain high extracellular Kϩ levels; both factors contributing to the hyperexcitability of subicular neurons to generate epileptiform activity. The functions of the astrocyte vascular interface may be more critical to the processes involved in epileptogenesis.

show abstract

“…The majority of neuroimaging research has focused on temporal lobe epilepsy (TLE), which is the most prevalent form of medically intractable epilepsy (Engel, 1996). The pathologic finding of MTS exists in up to 65% of cases of TLE (Babb et al, 1984). MTS is characterized histologically by cellular loss and hippocampal reorganization and is often identified on MRI by hippocampal atrophy and signal abnormalities (Berkovic et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Machine learning classification of mesial temporal sclerosis in epilepsy patients

Rudie¹,

Colby²,

Salamon

2015

Epilepsy Research

View full text Add to dashboard Cite

a b s t r a c tBackground and purpose: Novel approaches applying machine-learning methods to neuroimaging data seek to develop individualized measures that will aid in the diagnosis and treatment of brain-based disorders such as temporal lobe epilepsy (TLE). Using a large cohort of epilepsy patients with and without mesial temporal sclerosis (MTS), we sought to automatically classify MTS using measures of cortical morphology, and to further relate classification probabilities to measures of disease burden. Materials and methods: Our sample consisted of high-resolution T1 structural scans of 169 adults with epilepsy collected across five different 1.5 T and four different 3 T scanners at UCLA. We applied a multiple support vector machine recursive feature elimination algorithm to morphological measures generated from FreeSurfer's automated segmentation and parcellation in order to classify Epilepsy patients with MTS (n = 85) from those without MTS (N = 84). Results: In addition to hippocampal volume, we found that alterations in cortical thickness, surface area, volume and curvature in inferior frontal and anterior and inferior temporal regions contributed to a classification accuracy of up to 81% (p = 1.3 × 10 −17 ) in identifying MTS. We also found that MTS classification probabilities were associated with a longer duration of disease for epilepsy patients both with and without MTS. Conclusions: In addition to implicating extra-hippocampal involvement of MTS, these findings shed further light on the pathogenesis of TLE and may ultimately assist in the development of automated tools that incorporate multiple neuroimaging measures to assist clinicians in detecting more subtle cases of TLE and MTS.

show abstract

Distribution of Pyramidal Cell Density and Hyperexcitability in the Epileptic Human Hippocampal Formation

Cited by 247 publications

References 22 publications

Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus

Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus

Astrocytes and Epilepsy

Machine learning classification of mesial temporal sclerosis in epilepsy patients

Contact Info

Product

Resources

About