Transient Morphological Alterations in the Hippocampus After Pentylenetetrazole-Induced Seizures in Rats

Abstract

The relationships between seizures, neuronal death, and epilepsy remain one of the most disputed questions in translational neuroscience. Although it is broadly accepted that prolonged and repeated seizures cause neuronal death and epileptogenesis, whether brief seizures can produce a mild but similar effect is controversial. In the present work, using a rat pentylenetetrazole (PTZ) model of seizures, we evaluated how a single episode of clonic-tonic seizures affected the viability of neurons in the hippocampus, the area of the brain most vulnerable to seizures, and morphological changes in the hippocampus up to 1 week after PTZ treatment (recovery period). The main findings of the study were: (1) PTZ-induced seizures caused the transient appearance of massively shrunken, hyperbasophilic, and hyperelectrondense (dark) cells but did not lead to detectable neuronal cell loss. These dark neurons were alive, suggesting that they could cope with seizure-related dysfunction. (2) Neuronal and biochemical alterations following seizures were observed for at least 1 week. The temporal dynamics of the appearance and disappearance of dark neurons differed in different zones of the hippocampus. (3) The numbers of cells with structural and functional abnormalities in the hippocampus after PTZ-induced seizures decreased in the following order: CA1 > CA3b,c > hilus > dentate gyrus. Neurons in the CA3a subarea were most resistant to PTZ-induced seizures. These results suggest that even a single seizure episode is a potent stressor of hippocampal neurons and that it can trigger complex neuroplastic changes in the hippocampus.

Reference Gene Validation in the Brain Regions of Young Rats after Pentylenetetrazole-Induced Seizures

“…Seizures differentially affect different brain regions [21,27,33,34]. Loss of neurons and gliosis occurs in specific brain areas depending on the model used [35][36][37][38]. We also cannot exclude the possibility that expression stability may be affected by developmental factors, and our results are specific for young rats.…”

Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats

“…For example, a reduced level of EAAT2 protein expression was detected by immunohistochemical methods in the hippocampus of patients with temporal epilepsy [23], and decreased expression of glutamate transporters was reported in different animal models of epilepsy, including pilocarpine [25], kainite [27], and post-traumatic [26] models. Seizures may induce a transient increase in glutamate transporter expression, as observed in various studies [55,56,57]. Therefore, CTX treatment presumably will have more beneficial effects in the presence of reduced expression of transporters.…”

Antagonism of Histamine H3 receptors Alleviates Pentylenetetrazole-Induced Kindling and Associated Memory Deficits by Mitigating Oxidative Stress, Central Neurotransmitters, and c-Fos Protein Expression in Rats

“…Several antioxidant compounds were found to mitigate memory impairment in different animal models [47][48][49][50][51][52][53]. Therefore, evaluating numerous oxidative stress markers (e.g., malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD)) of PTZ-kindled animals were carried out to assess the effects of the novel H3R antagonist E177.…”