Etiology-related Degree of Sprouting of Parvalbumin-immunoreactive Axons in the Human Dentate Gyrus in Temporal Lobe Epilepsy

Object Hippocampal sclerosis can be identified in most patients with mesial temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is widely performed to treat patients with drug-resistant mesial TLE. In general, both epilepsy-prone and epilepsy-resistant neurons are believed to be in the hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are usually considered one of the most vulnerable types of neurons. The aim of this study was to clarify the fate of mossy cells in the hippocampus in epileptic humans. Methods Of the 19 patients included in this study, 15 underwent temporal lobe resection because of drug-resistant TLE. Four patients were used as controls because they harbored tumors that had not invaded the hippocampus and they had experienced no seizures. Histological evaluation of resected hippocampal tissues was performed using immunohistochemistry. Results Mossy cells were identified in the control as well as the epileptic hippocampi by using cocaine- and amphetamine-regulated transcript peptide immunohistochemistry. In most cases the number of mossy cells was reduced and thorny excrescences were smaller in the epileptic hippocampi than in controls; however, there was a significant loss of pyramidal cells and a partial loss of granule cells in the same epileptic hippocampi in which mossy cell loss was apparent. The loss of mossy cells could be correlated with the extent of hippocampal sclerosis, patient age at seizure onset, duration of epilepsy, and frequency of seizures. Conclusions In many cases large numbers of mossy cells were present in the hilus of the dentate gyrus when most pyramidal neurons of the CA1 and CA3 areas of the Ammon's horn were lost, suggesting that mossy cells may not be more vulnerable to epileptic seizures than the hippocampal pyramidal neurons.

Download Full-text

Hyperpolarization-activated cation current Ih of dentate gyrus granule cells is upregulated in human and rat temporal lobe epilepsy

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2012.02.133 ◽

2012 ◽

Vol 420 (1) ◽

pp. 156-160 ◽

Cited By ~ 22

Author(s):

Rainer Surges ◽

Maria Kukley ◽

Amy Brewster ◽

Christiane Rüschenschmidt ◽

Johannes Schramm ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Dentate Gyrus ◽

Temporal Lobe ◽

Granule Cells ◽

Cation Current

Download Full-text

Seizure frequency correlates with loss of dentate gyrus GABAergic neurons in a mouse model of temporal lobe epilepsy

The Journal of Comparative Neurology ◽

10.1002/cne.24226 ◽

2017 ◽

Vol 525 (11) ◽

pp. 2592-2610 ◽

Cited By ~ 26

Author(s):

Paul S. Buckmaster ◽

Emily Abrams ◽

Xiling Wen

Keyword(s):

Mouse Model ◽

Temporal Lobe Epilepsy ◽

Dentate Gyrus ◽

Temporal Lobe ◽

Seizure Frequency ◽

Gabaergic Neurons

Download Full-text

Temporal Patterns of Fos Expression in the Dentate Gyrus after Spontaneous Seizures in a Mouse Model of Temporal Lobe Epilepsy

Journal of Neuroscience ◽

10.1523/jneurosci.0838-05.2005 ◽

2005 ◽

Vol 25 (31) ◽

pp. 7210-7220 ◽

Cited By ~ 62

Author(s):

Z. Peng

Keyword(s):

Mouse Model ◽

Temporal Lobe Epilepsy ◽

Dentate Gyrus ◽

Temporal Lobe ◽

Temporal Patterns ◽

Spontaneous Seizures ◽

Fos Expression

Download Full-text

Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy

Brain Sciences ◽

10.3390/brainsci10090634 ◽

2020 ◽

Vol 10 (9) ◽

pp. 634

Author(s):

Guillermo González-H ◽

Itzel Jatziri Contreras-García ◽

Karla Sánchez-Huerta ◽

Claudio M. T. Queiroz ◽

Luis Ricardo Gallardo Gudiño ◽

...

Keyword(s):

Synaptic Plasticity ◽

Temporal Lobe Epilepsy ◽

Dentate Gyrus ◽

Temporal Lobe ◽

Focal Epilepsy ◽

Chronic Phase ◽

Long Term Potentiation ◽

Excitatory Postsynaptic Potential ◽

Output Curve

Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium–pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE.

Download Full-text

Spontaneous Excitatory Currents and κ-Opioid Receptor Inhibition in Dentate Gyrus Are Increased in the Rat Pilocarpine Model of Temporal Lobe Epilepsy

Journal of Neurophysiology ◽

10.1152/jn.1997.78.4.1860 ◽

1997 ◽

Vol 78 (4) ◽

pp. 1860-1868 ◽

Cited By ~ 22

Author(s):

Michele L. Simmons ◽

Gregory W. Terman ◽

Charles Chavkin

Keyword(s):

Temporal Lobe Epilepsy ◽

Dentate Gyrus ◽

Opioid Receptor ◽

Temporal Lobe ◽

Mossy Fiber ◽

Perforant Path ◽

Mossy Fiber Sprouting ◽

Receptor Inhibition ◽

Excitatory Activity ◽

Pilocarpine Model

Simmons, Michele L., Gregory W. Terman, and Charles Chavkin. Spontaneous excitatory currents and κ-opioid receptor inhibition in dentate gyrus are increased in the rat pilocarpine model of temporal lobe epilepsy. J. Neurophysiol. 78: 1860–1868, 1997. Temporal lobe epilepsy is associated with a characteristic pattern of synaptic reorganization in the hippocampal formation, consisting of neuronal loss and aberrant growth of mossy fiber collaterals into the dentate gyrus inner molecular layer. We have used the rat pilocarpine model of temporal lobe epilepsy to study the functional consequences of mossy fiber sprouting on excitatory activity and κ-opioid receptor-mediated inhibition. Using the whole cell voltage-clamp technique, we found that abnormal excitatory activity was evident in granule cells of the dentate gyrus from pilocarpine-treated rats. The frequency of spontaneous excitatory postsynaptic currents (EPSCs) was increased greatly in cells from tissue in which significant mossy fiber sprouting had developed. In the presence of bicuculline, giant spontaneous EPSCs, with large amplitudes and long durations, were seen only in association with mossy fiber sprouting. Giant EPSCs also could be evoked by low-intensity stimulation of the perforant path. Mossy fibers release not only excitatory amino acids, but also opioid peptides. κ-Opioid receptor-mediated inhibition in normal Sprague-Dawley rats was seen only in hippocampal sections from the ventral pole. In pilocarpine-treated rats, however, kappa receptor-mediated effects were seen in both ventral and more dorsal sections. Thus in this model of temporal lobe epilepsy, several types of abnormal excitatory activity were observed, thereby supporting the idea that mossy fiber sprouting leads to recurrent excitatory connections. At the same time, inhibition of excitatory activity by κ-opioid receptors was increased, perhaps representing an endogenous anticonvulsant mechanism.

Download Full-text