Effects of pentylenetetrazole-induced status epilepticus on behavior, emotional memory and learning in immature rats

Erdoğan, Füsun; Gölgeli, Asuman; Küçük, Ayşegül; Arman, Fehim; Karaman, Yahya; Ersoy, Ali Özdemir

doi:10.1016/j.yebeh.2005.03.002

Cited by 19 publications

(17 citation statements)

References 42 publications

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“…It may also explain the failure of PTZ-induced SE between P16 to P20 to result in deficits in the performance of an elevated T-maze or result in permanent changes in behavior 74, 85…”

Section: Se Outcome: An Interaction Between Age and Inciting Stimulusmentioning

confidence: 99%

Lessons From the Laboratory: The Pathophysiology, and Consequences of Status Epilepticus

Rajasekaran

Zanelli

Goodkin

2010

Seminars in Pediatric Neurology

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Status epilepticus (SE) is the most common neurological emergency of childhood. Experimental models parallel several clinical features of SE including: (1) treatment is complicated by an increasing probability that benzodiazepines will fail with increasing seizure duration and (2) outcome varies with age and etiology. Studies using these models demonstrated that the activity-dependent trafficking of GABA A receptors contributes, in part, to the progressive decline in GABA-mediated inhibition and the failure of the benzodiazepines. Furthermore, laboratory studies have provided evidence that age and inciting stimulus interact to determine the neuronal circuits activated during SE (i.e. functional anatomy), and that differences in functional anatomy can partially account for variations in SE outcome. Future laboratory studies are likely to provide an additional understanding of the cellular and molecular mechanisms that underlie SE and its consequences. Such studies are necessary in the development of rational emergent therapy for SE and its long term outcomes.The majority of seizures stop spontaneously. However, when the mechanisms that terminate a seizure fail, the result is a prolonged, self-sustaining seizure that can be refractory to treatment. This condition, which has been termed status epilepticus (SE), represents the most common neurological emergency of childhood with an estimated incidence of 10-27/100,000/ year for children between the ages of 1 month and 15 years with the majority of episodes occurring in children <4 years. 1-5 Fortunately for many children, SE occurs without apparent consequences; however, for others, SE results in death or long term neurological dysfunction or potentially epilepsy1 , 6 -14The intent of translational research focused on the pathogenesis and long term outcome of SE is to gain a better understanding of the mechanisms that underlie this childhood emergency with the goal of reducing its associated mortality and morbidity to even lower levels. The ethical and practical limitations of performing such studies in children are well known. 15 Furthermore, current clinical techniques do not yet provide the resolution required to completely address questions at the cellular and molecular levels in human studies. Therefore, many questions regarding basic mechanisms are still best addressed using in vivo animal models that, for the Corresponding author: Howard P. Goodkin, MD PhD, Box 800394, Charlottesville, VA 22908, 434-924-8378 (office), 434-982-1726 (fax), hpg9v@virginia.edu. Disclosures: KR received support from the Epilepsy Foundation, SAZ receives support from the Epilepsy Foundation and NIH (NS063118). HPG receives support from the NIH (NS048413, NS067439) and has served as a consultant to MedImmune, Inc. within the last 3 years.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, type...

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“…It may also explain the failure of PTZ-induced SE between P16 to P20 to result in deficits in the performance of an elevated T-maze or result in permanent changes in behavior 74, 85…”

Section: Se Outcome: An Interaction Between Age and Inciting Stimulusmentioning

confidence: 99%

Lessons From the Laboratory: The Pathophysiology, and Consequences of Status Epilepticus

Rajasekaran

Zanelli

Goodkin

2010

Seminars in Pediatric Neurology

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“…In the same laboratory, in a careful study with P5, P10, P20, P30, P60 rats subjected to kainate‐induced SE, Stafstrom et al (1993) showed that long‐term cognitive and behavioral deficits did not occur in the neonatal group (P5–P10), but that deficits were moderate in the P30 and severe in the P60 rats. In the same group, Cilio et al (2003), reported that after a lithium–pilocarpine‐induced SE in P20 pups, the adult rats displayed various intellectual and behavioral problems; however, Ergodan et al (2005) failed to find such long‐term deficits with the same model. In another laboratory, Lynch et al (2000) using like Stafstrom et al (1993) kainate‐induced SE in neonatal pups (P1 to P14), investigators found in contrast to Stafstrom that all rats developed “life‐long” multiple severe deficits (Lynch et al, 2000).…”

Section: Relevance Of Animal Model Data To Clinical Observationsmentioning

confidence: 99%

Neonatal Seizures: Gaps Between the Laboratory and the Clinic

Lombroso

2007

Epilepsia

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Summary: Seizures in neonates (NBs) remain the most frequent neurological problem in the nursery. Considerable debate about their consequences exists between data and deductions reached through animal experimentations and those obtained through clinical investigations. The main conflicting issues are whether seizures in NBs can plant the roots for epileptogenesis and cause long-term deficits. The purpose of this chapter is to evaluate both laboratory and clinical results. Methods: Clinical data will be presented, including a 20-yearlong cohort of NBs. This will be followed by the main seminal discoveries obtained in neonatal models. The phenomenon of transient or persistent dysmaturity following NB seizures will be discussed in relation to etiological factors. Results: The findings and deductions from animal models support the notions that epileptogenesis and cognitive deficits result from NB seizures. These conclusions contrast with clinical investigations maintaining that NB seizures, per se, are symptomatic markers of preexisting or of ongoing morbidities. The reasons for contrasting views will be discussed. Suggestions will be advanced for more animal models whose seizures are consistent with the etiologies and the phenotypes of human NB seizures.

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“…In a study evaluating the effects of SE on behavior, memory, and learning in immature and mature rats, it was shown that cognitive damage occurs in rats after SE, but that cognitive impairment in immature rats is not as severe as in mature groups (23). In another study, it was reported that immature rats had transient behavioral changes following PTZ-induced SE and had no problems in emotional memory or learning (24). In a study assessing immature rats 60 days after lithiumpilocarpine-induced SE, impaired cognition and reduced anxiety were observed, and it has been reported that seizures during early life may lead to cognitive impairment and behavioral disturbance in the long term (25).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Behavior, Learning, Memory Along with Apoptosis, Neuronal Damage, and GABA-A Alpha-1 Receptor Level After Status Epilepticus in Immature and Mature Rats

Sönmez¹,

Göl²,

Erdoğan³

et al. 2018

tnd

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Objective: In this study, we aimed to evaluate age-dependent cognitive and behavioral changes, neuronal damage, and the amount of gamma-aminobutyric acid-A (GABA-A) alpha 1 in immature, mature, and adolescant rats after status epilepticus (SE). Materials and Methods: SE was induced in immature (17 days), adolescant (45 days), and mature (150 days) rats using pentylenetetrazole (PTZ). After SE, adolescant and mature rats underwent open field test and Morris water maze test. After behavioral tests, the animals were sacrificed and we performed histologic investigations on the immature, adolescant, and mature rats to assess neuronal cell damage (caspase and calpain activity) and amount of GABA-A alpha 1 receptor and compared them with a control group. Results: There were no statistically significant differences between the control and experimental groups in behavioral tests in the early stage after SE. Calpainmediated neuronal damage was observed in mature rats with necrotic morphology after SE, but this was not observed in adolescant and immature rats. Caspasemediated neuronal damage was observed in immature rats with apoptotic morphology after SE. The amount of GABA-A alpha 1 receptor was decreased in the three experimental groups compared with the control groups. The decrease in GABA-A alpha 1 receptor amount was highest in the mature experimental group. The amount of GABA-A alpha 1 receptor in the hippocampus decreased to level higher than in the cortex. Conclusion: This study show that there is no negative impact on learning and behavioral functions in the early stage after PTZ-induced SE, but histologically led to necrosis dominant calpain and caspase-mediated neuronal damage, calpain-mediated cell necrosis is seen particularly in the mature group and caspasedependent apoptotic morphology observed in immature rats.The decreased of GABA-A alpha 1 receptor is highest in the adults. Our study supports that SEinduced cell damage is more pronounced with increased age, and calpain-mediated cell damage that can clearly be observed in the mature group. Long-term follow-up studies are needed to understand the long-term effect of SE-dependent neuronal damage on cognition and behavior.

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Effects of pentylenetetrazole-induced status epilepticus on behavior, emotional memory and learning in immature rats

Cited by 19 publications

References 42 publications

Lessons From the Laboratory: The Pathophysiology, and Consequences of Status Epilepticus

Lessons From the Laboratory: The Pathophysiology, and Consequences of Status Epilepticus

Neonatal Seizures: Gaps Between the Laboratory and the Clinic

Evaluation of Behavior, Learning, Memory Along with Apoptosis, Neuronal Damage, and GABA-A Alpha-1 Receptor Level After Status Epilepticus in Immature and Mature Rats

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