Effects of age on kindling and kindled seizure-induced increase of benzodiazepine receptor binding

Fanelli, Richard J.; McNamara, James O

doi:10.1016/0006-8993(86)91393-4

Cited by 37 publications

(17 citation statements)

References 12 publications

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“…2 We also found no change in GABA or flunitrazepam binding to the PSD fraction from cerebral cortex in our kindled animals. Previous reports detected an increase in benzodiazepine-binding sites (50)(51)(52)(53) and either an increase (51) or no change (50) in GABA-binding sites after kindling, but some of these changes were transient; different results were obtained with washed or unwashed membrane preparations (54), and the pharmacological effects of GABA antagonists on the kindled state were equivocal (55).…”

Section: Resultsmentioning

confidence: 92%

Effect of septal kindling on glutamate binding and calcium/calmodulin-dependent phosphorylation in a postsynaptic density fraction isolated from rat cerebral cortex.

Wasterlain

Sachs

et al. 1990

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

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Postsynaptic density (PSD) fractions were isolated from the cerebral cortices of control and kindled rats and assayed for glutamate and y-aminobutyric acid-binding capacities and for the Ca2+/calmodulin-dependent protein kinase. Glutamate binding was found to be increased by =50% in the PSDs isolated from kindled rats as compared to controls; this increase was almost completely from an increase in B..;Kd decreased only slightly. Studies with inhibitors indicate that the receptors involved were of the N-methyl-D-aspartate and quisqualate types. PSDs isolated from control and kindled rats did not differ in y-aminobutyric acid or flunitrazepam binding.The in vitro autophosphorylation of the Ca2+/calmodulindependent protein kinase was depressed by 45-76% in PSDs isolated from kindled rats as compared to controls, with little change in amount of the kinase. Therefore, we infer that (i) the kindled state is associated with an increase in glutamate activation of postsynaptic sites, allowing Ca21 to enter dendritic spines, (ii) a change has occurred in activity ofthe protein kinase, which is the major cerebral cortex PSD protein, and (iii) perhaps major alterations in the PSD are a concomitant to the long-lasting nature of the kindled state.Kindling is the term coined by Goddard (1) to describe the progressive development, in response to initially subthreshold electrical stimulation of specific brain sites, of epileptic seizures that progressively spread and increase in intensity. Progression of the kindling phenomenon is characterized by increases in after-discharge duration and amplitude (2-5), a spread to secondary sites (5, 6), and decreases in threshold in distant cortical sites (2). Kindling shows remarkable temporal and spatial specificity as seen in many species from frog (7) to subhuman primates (8) and, once established, may persist without further stimulation for the life of the animal (9). After sufficient training, some animals develop spontaneous seizures (10). Strong pharmacological evidence indicates that this phenomenon is generated through stimulation of identifiable synaptic populations (11). Kindling by stimulation of the medial septal nuclei is associated with a decrease in the activity of the enzyme calmodulin kinase II in cortex and hippocampus (12, 13). However, calmodulin kinase II is a ubiquitous enzyme in brain. It is present in the presynaptic apparatus (14) where it may regulate transmitter biosynthesis by phosphorylation of 5-tyrosine and 5-tryptophan hydroxylases (15) and may regulate transmitter release via synapsin I phosphorylation (16). The enzymatic activity is also present in large quantities postsynaptically, particularly in postsynaptic densities (17), and calmodulin kinase II appears identical to the major postsynaptic density (PSD) protein (18)(19)(20). The goal of our study was to investigate whether any biochemical changes in isolated PSDs, such as neurotransmitter binding and phosphorylations, were associated with septal kindling. METHODSKindling. Male Sprague-Dawley r...

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Section: Resultsmentioning

confidence: 92%

Effect of septal kindling on glutamate binding and calcium/calmodulin-dependent phosphorylation in a postsynaptic density fraction isolated from rat cerebral cortex.

Wasterlain

Sachs

et al. 1990

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

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“…Kindling is the repeated low-frequency electrical stimulation of brain structures (usually limbic) that produces spontaneous epileptiform activity after weeks to months [13]. The epileptiform activity persists after cessation of electrical stimulation and may be permanent, producing acute seizures that can lead to hippocampal lesions [14,15,16]. Induction of paroxysmal behaviour in the cellular elements of a previously normal neural network by an Fig.…”

Section: Resultsmentioning

confidence: 99%

Extratemporal hypometabolism on FDG PET in temporal lobe epilepsy as a predictor of seizure outcome after temporal lobectomy

Choi

Kim

Hong

et al. 2003

Eur J Nucl Med Mol Imaging

108

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We investigated the relationship between the presence of extratemporal hypometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and seizure outcome after temporal lobectomy in patients with medically intractable temporal lobe epilepsy (TLE). In 47 patients with intractable unilateral mesial TLE, regional metabolic changes on FDG PET images obtained during the 2 months preceding anterior temporal lobectomy were compared with postoperative seizure outcome. Postoperative seizure outcome was evaluated with a mean follow-up period of 6.1+/-0.6 years (range 5.2-7.2 years). Forty-two (89%) of the 47 patients achieved a good postoperative seizure outcome (Engel class I or II). All patients had hypometabolism in the temporal cortex ipsilateral to the epileptogenic region on FDG PET scans. Fourteen (78%) of the 18 patients with hypometabolism only in the ipsilateral temporal cortex were completely seizure free (Engel class Ia) after surgery. In contrast, five (45%) of the 11 patients with extratemporal cortical hypometabolism confined to the ipsilateral cerebral hemisphere and only four (22%) of the 18 patients with hypometabolism in the contralateral cerebral cortex were completely seizure free after surgery. The postoperative seizure-free rates were significantly different across the three groups of patients with different cortical metabolic patterns ( P<0.005). Furthermore, all of the nine patients with a non-class I outcome (Engel class II-IV) had extratemporal (including contralateral temporal) cortical hypometabolism. Thalamic hypometabolism was noted in 20 (43%) of the 47 patients (ipsilateral in 12, bilateral in 8). Sixteen (59%) of the 27 patients with normal thalamic metabolism were completely seizure free after surgery, while only seven (35%) of the 20 patients with thalamic hypometabolism became completely seizure free ( P<0.05). Multivariate analysis revealed that among variables including clinical, EEG, magnetic resonance imaging, pathological and FDG PET metabolic findings, only cortical metabolic pattern was an independent factor for the prediction of postoperative seizure outcome ( P<0.005). It is concluded that extratemporal cortical hypometabolism outside the seizure focus, in particular hypometabolism in the contralateral cerebral cortex, may be associated with a poorer postoperative seizure outcome in TLE and may represent underlying pathology that is potentially epileptogenic. Thalamic hypometabolism, which was associated, but not independently, with a higher likelihood of postoperative seizures, may be secondary to extratemporal or temporal pathology.

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“…The animal was then stimulated at 125% of the AD threshold daily for several weeks. The animal was considered kindled when stage 5 motor seizures (see below) were elicited over three consecutive days ( Fanelli and McNamara, 1986 , Reddy et al, 2010 , Jeffrey et al, 2014 ). An ascending series was similarly conducted in each kindled animal.…”

Section: Methodsmentioning

confidence: 99%

“…Experimental investigation using animal models may help explore this issue. However, studies that compare seizure susceptibility between young and aging/aged animals remain scarce ( de Toledo-Morrell et al, 1984 , Fanelli and McNamara, 1986 , Leppik et al, 2006 , Kelly, 2010 , Hattiangady et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Susceptibility to hippocampal kindling seizures is increased in aging C57 black mice

et al. 2017

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Effects of age on kindling and kindled seizure-induced increase of benzodiazepine receptor binding

Cited by 37 publications

References 12 publications

Effect of septal kindling on glutamate binding and calcium/calmodulin-dependent phosphorylation in a postsynaptic density fraction isolated from rat cerebral cortex.

Effect of septal kindling on glutamate binding and calcium/calmodulin-dependent phosphorylation in a postsynaptic density fraction isolated from rat cerebral cortex.

Extratemporal hypometabolism on FDG PET in temporal lobe epilepsy as a predictor of seizure outcome after temporal lobectomy

Susceptibility to hippocampal kindling seizures is increased in aging C57 black mice

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