Longitudinal variation in cell density and mossy fiber reorganization in the dentate gyrus from temporal lobe epileptic patients

Masukawa, Leona M.; O'Connor, William M.; Lynott, J.; Burdette, Linda J.; Uruno, Katsuhisa; McGonigle, Paul; O’Connor, Michael J.

doi:10.1016/0006-8993(95)00167-o

Cited by 43 publications

(23 citation statements)

References 44 publications

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“…2a3 and Fig. 2b3 respectively) as described elsewhere (Masukawa et al, 1995). Moreover, Nissl's staining revealed moderate to severe neuronal loss in different areas of the brain of chronic epileptic rats experiencing more than one month of SE (Fig.…”

Section: Down-regulation Of Bk Channels In Axons and Terminal Fields supporting

confidence: 64%

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Otalora¹,

Hernandez²,

Arshadmansab³

et al. 2008

Brain Research

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In the hippocampus, BK channels are preferentially localized in presynaptic glutamatergic terminals including mossy fibers where they are thought to play an important role regulating excessive glutamate release during hyperactive states. Large conductance calcium-activated potassium channels (BK, MaxiK, Slo) have recently been implicated in the pathogenesis of genetic epilepsy. However, the role of BK channels in acquired mesial temporal lobe epilepsy (MTLE) remains unknown. Here we used immunohistochemistry, laser scanning confocal microscopy (LSCM), western immunoblotting and RT-PCR to investigate the expression pattern of the alpha-pore forming subunit of BK channels in the hippocampus and cortex of chronically epileptic rats obtained by the pilocarpine model of MTLE. All epileptic rats experiencing recurrent spontaneous seizures exhibited a significant down-regulation of BK channel immunostaining in the mossy fibers at the hilus and stratum lucidum of the CA3 area. Quantitative analysis of immunofluorescence signals by LSCM revealed a significant 47% reduction in BK channel in epileptic rats when compared to age-matched non-epileptic control rats. These data correlate with a similar reduction in BK channel protein levels and transcripts in the cortex and hippocampus. Our data indicate a seizure-related down-regulation of BK channels in chronically epileptic rats. Further functional assays are necessary to determine whether altered BK channel expression is an acquired channelopathy or a compensatory mechanism affecting the network excitability in MTLE. Moreover, seizure-mediated BK down-regulation may disturb neuronal excitability and presynaptic control at glutamatergic terminals triggering exaggerated glutamate release and seizures.

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Section: Down-regulation Of Bk Channels In Axons and Terminal Fields supporting

confidence: 64%

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Otalora¹,

Hernandez²,

Arshadmansab³

et al. 2008

Brain Research

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“…In cases that were graded differently, we used the Wyler score determined from the slices studied in our laboratory. This discrepancy might account to variation of the degree of sclerosis along the longitudinal axis of the hippocampus, as shown previously for the dentate gyrus (Masukawa et al, 1995). In addition to the HS score, the presence of granule cell dispersion was determined.…”

Section: Methodsmentioning

confidence: 95%

Stimulus and Potassium-Induced Epileptiform Activity in the Human Dentate Gyrus from Patients with and without Hippocampal Sclerosis

Gabriel¹,

Njunting²,

Pomper³

et al. 2004

J. Neurosci.

155

102

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Hippocampal specimens resected to cure medically intractable temporal lobe epilepsy (TLE) provide a unique possibility to study functional consequences of morphological alterations. One intriguing alteration predominantly observed in cases of hippocampal sclerosis is an uncommon network of granule cells monosynaptically interconnected via aberrant supragranular mossy fibers. We investigated whether granule cell populations in slices from sclerotic and nonsclerotic hippocampi would develop ictaform activity when challenged by low-frequency hilar stimulation in the presence of elevated extracellular potassium concentration (10 and 12 mM) and whether the experimental activity differs according to the presence of aberrant mossy fibers.We found that ictaform activity could be evoked in slices from sclerotic and nonsclerotic hippocampi (27 of 40 slices, 14 of 20 patients; and 11 of 22 slices, 6 of 12 patients, respectively). However, the two patient groups differed with respect to the pattern of ictaform discharges and the potassium concentration mandatory for its induction. Seizure-like events were already induced with 10 mM K ϩ . They exclusively occurred in slices from sclerotic hippocampi, of which 80% displayed stimulus-induced oscillatory population responses (250 -300 Hz). In slices from nonsclerotic hippocampi, atypical negative field potential shifts were predominantly evoked with 12 mM K ϩ . In both groups, the ictaform activity was sensitive to ionotropic glutamate receptor antagonists and lowering of [Ca 2ϩ ] o . Our results show that, in granule cell populations of hippocampal slices from TLE patients, high K ϩ -induced seizure-like activity and ictal spiking coincide with basic electrophysiological abnormalities, hippocampal sclerosis, and mossy fiber sprouting, suggesting that network reorganization could play a crucial role in determining type and threshold of such activity.

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“…In addition, mossy fiber sprouting has been observed in adult animals after electrical (Sutula et al, 1988(Sutula et al, , 1996Cavazos et al, 1991) or PTZ (Golarai et al, 1992) kindling. Mossy fiber sprouting has also been found in pathological specimens removed from patients with temporal lobe epilepsy (Sutula et al, 1989;Houser et al, 1990;Babb et al, 1991;Isokawa et al, 1993;Masukawa et al, 1995). There is also a considerable amount of indirect evidence that these new neurites establish functional synaptic connections (Tauck and Nadler, 1985;Represa and Ben-Ari, 1992;Represa et al, 1993;Okazaki et al, 1995;Wuarin and Dudek, 1996).…”

Section: Mossy Fiber Sproutingmentioning

confidence: 93%

Mossy fiber sprouting after recurrent seizures during early development in rats

et al. 1999

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Longitudinal variation in cell density and mossy fiber reorganization in the dentate gyrus from temporal lobe epileptic patients

Cited by 43 publications

References 44 publications

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Stimulus and Potassium-Induced Epileptiform Activity in the Human Dentate Gyrus from Patients with and without Hippocampal Sclerosis

Mossy fiber sprouting after recurrent seizures during early development in rats

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