An early decrease in cell proliferation after pentylenetetrazole-induced seizures

Aniol, V. A.; Stepanichev, M. Yu.; Лазарева, Н. А.; Gulyaeva, N. V.

doi:10.1016/j.yebeh.2011.08.002

Cited by 19 publications

(18 citation statements)

References 65 publications

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“…In our previous study, we demonstrated that a single PTZ evoked epileptic seizure results in a significant increase in BrdU labeling of cells in the SVZ and hip pocampal DG on the next day after the seizure [8], which corresponds well to the data that have been reported by other authors [3,6]. The further fate of the cells that were generated in the course of enhanced seizure induced proliferation remains poorly under stood.…”

Section: Resultssupporting

confidence: 88%

“…There is evidence that a substantial portion of these cells die during several weeks or months after the seizure but not in all seizure models. Indeed, after a comparison of the number of BrdU+ cells in the DG on the next day after the seizure [6,8] and 3 months later (Fig. 2) we concluded that only one third of the labeled cells survived for 3 months.…”

Section: Resultsmentioning

confidence: 86%

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Ultra-low doses of tetrahydrocannabinol contribute to the survival of newly-born cells in the dentate gyrus of adult rats

2015

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It was shown previously that a single episode of pentylenetetrazole induced generalized seizures was accompanied by learning and memory impairments in rodents. The temporal profile of these impair ments suggests that their development at least partially was determined by changes in adult neurogenesis. On the other hand, the cannabinoid receptor agonist tetrahydrocannabinol is known for its protective effect ver sus seizure induced cognitive impairments. The aim of our present study was to determine whether tetrahy drocannabinol affects the process of adult neurogenesis in the hippocampus, and whether there is a link between tetrahydrocannabinol induced changes in adult neurogenesis and memory function in rats. We dis covered that tetrahydrocannabinol applied at an ultra low dose (2 µg/kg) at early stages of differentiation contributes to better survival of newly born cells in the hippocampus. We also established a significant corre lation between the number of newly born cells that survived in the hippocampus after 3 months and the long term memory in rats. This finding may indicate that the protective effect of tetrahydrocannabinol on young hippocampal cells may participate in its cognitive effect.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 86%

Ultra-low doses of tetrahydrocannabinol contribute to the survival of newly-born cells in the dentate gyrus of adult rats

2015

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“…First is the question of whether dark cells appear in the rat brain after single doses of 70-80 mg/kg of PTZ, eliciting convulsions [13], or whether dark cells can only be seen as a result of repeated dosage with PTZ [14], as there are reports of the brains of animals with severe convulsive manifestations and the visible absence of the same [10]. According to the results obtained here, PTZ kindling in mice, preceding convulsive syndrome, is an indispensable condition for detecting dark cells in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…Little is known of the further fate of dark cells after the occurrence of a pathological focus in the brain; such data are required for a better understanding of their nature [28,35,47]. Results from complex studies of the processes of the degeneration of mature neurons and the proliferation of young neurons in nervous tissue growth areas have been reported recently [14,24,33,48,55]. Studies in this direction may throw light on the general problem of the cellular mechanisms of epilepsy.…”

Section: Discussionmentioning

confidence: 99%

“…Extensive data have been obtained on the ability of NMDA-type receptor antagonists to suppress the development of the convulsive manifestations of PTZ kindling in mice and rats [9,29,41,42,56]. Modeling of PTZ kindling also produces morphological and histochemical changes to neurons [10,11,14,27,58]. It is not entirely clear that convulsions are the direct cause of these changes and that these changes are always evidence of neuron degeneration and death.…”

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confidence: 99%

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The Ability of NMDA-Type Glutamate Receptor Blockers to Prevent the Development of Pentylenetetrazole Kindling and Morphological Changes to Pyramidal Neurons in the Mouse Hippocampus

Vasilev

Туманова

Lavrent’eva

et al. 2015

Neurosci Behav Physi

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Experiments on mice addressed the link between convulsive syndrome and morphological changes in hippocampal neurons occurring on development of pentylenetetrazole (PTZ) kindling. Kindling was induced by i.p. PTZ (35 mg/kg) three times a week for one month. By the end of this period, 70% of the mice responded to administration of PTZ with severe clonic or clonic-tonic seizures. Hippocampal sections (stratum pyramidale, field CA1, Nissl staining) from convulsive mice showed large numbers of altered cells (24.7 ± 2.1%). Most of these were pyramidal neurons. These hyperchromic neurons had reduced body sizes, loss of turgor, wrinkling of the cell body, and deformation of dendritic processes. These dark-type changes were present in 2.3 ± 2.1% of neurons in the hippocampus of intact mice and mice resistant to the convulsogenic effect of PTZ (30% of the population). Immunohistochemical studies demonstrated normal expression of NeuN (Fox3) protein in all hippocampal cells, including dark hyperchromic neurons. This is evidence that neurons did not die en masse and were relatively viable. Prophylactic s.c. administration of NMDA receptor blockers (0.5 mg/kg memantine, 0.1 mg/kg IEM-1921, or 1 mg/kg IEM-1958) decreased the proportion of mice developing PTZ kindling from 70% to 40%. The proportion of altered neurons in the 60% of mice given NMDA blockers and not developing PTZ kindling or convulsions in the presence of blockers was 0.1 ± 0.06%, which was the same as in intact mice. Conversely, the hippocampus of mice demonstrating convulsions despite simultaneous administration of NMDA blockers showed 24.0 ± 5.6% hyperchromic neurons. These results provide evidence that pathologically altered neurons appeared after convulsive seizures in animals after PTZ kindling and that blockade of NMDA glutamate receptors could weaken both the development of convulsive syndrome and the concomitant morphological changes to hippocampal neurons.

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N‐methyl‐D‐aspartate receptor channel blockers prevent pentylenetetrazole‐induced convulsions and morphological changes in rat brain neurons

Zaitsev

Kim

Vasilev

et al. 2014

J of Neuroscience Research

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Alterations in inhibitory and excitatory neurotransmission play a central role in the etiology of epilepsy, with overstimulation of glutamate receptors influencing epileptic activity and corresponding neuronal damage. N-methyl-D-aspartate (NMDA) receptors, which belong to a class of ionotropic glutamate receptors, play a primary role in this process. This study compared the anticonvulsant properties of two NMDA receptor channel blockers, memantine and 1-phenylcyclohexylamine (IEM-1921), in a pentylenetetrazole (PTZ) model of seizures in rats and investigated their potencies in preventing PTZ-induced morphological changes in the brain. The anticonvulsant properties of IEM-1921 (5 mg/kg) were more pronounced than those of memantine at the same dose. IEM-1921 and memantine decreased the duration of convulsions by 82% and 37%, respectively. Both compounds were relatively effective at preventing the tonic component of seizures but not myoclonic seizures. Memantine significantly reduced the lethality caused by PTZ-induced seizures from 42% to 11%, and all animals pretreated with IEM-1921 survived. Morphological examination of the rat brain 24 hr after administration of PTZ revealed alterations in the morphology of 20-25% of neurons in the neocortex and the hippocampus, potentially induced by excessive glutamate. The expression of the excitatory amino acid transporter 1 protein was increased in the hippocampus of the PTZ-treated rats. However, dark neurons did not express caspase-3 and were immunopositive for the neuronal nuclear antigen protein, indicating that these neurons were alive. Both NMDA antagonists prevented neuronal abnormalities in the brain. These results suggest that NMDA receptor channel blockers might be considered possible neuroprotective agents for prolonged seizures or status epilepticus leading to neuronal damage.

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An early decrease in cell proliferation after pentylenetetrazole-induced seizures

Cited by 19 publications

References 65 publications

Ultra-low doses of tetrahydrocannabinol contribute to the survival of newly-born cells in the dentate gyrus of adult rats

Ultra-low doses of tetrahydrocannabinol contribute to the survival of newly-born cells in the dentate gyrus of adult rats

The Ability of NMDA-Type Glutamate Receptor Blockers to Prevent the Development of Pentylenetetrazole Kindling and Morphological Changes to Pyramidal Neurons in the Mouse Hippocampus

N‐methyl‐D‐aspartate receptor channel blockers prevent pentylenetetrazole‐induced convulsions and morphological changes in rat brain neurons

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