Vulnerability of Developing Rat Brain to Electroconvulsive Seizures

Wasterlain, Claude G.; Plum, Fred

doi:10.1001/archneur.1973.00490250056006

Cited by 164 publications

(59 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This study indicates that following recurrent seizures in the neonatal rat, there is a reduction in newly born granule cells. These seizure-induced decreases in neurogenesis is consistent with prior studies by Wasterlain and colleagues [89][90][91] who concluded that recurrent neonatal seizures, while not causing cell death, resulted in reduced cell number.…”

Section: Recurrent Seizuressupporting

confidence: 90%

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

Holmes¹,

Zhao²

2008

Pediatric Neurology

View full text Add to dashboard Cite

Epilepsy is a chronic condition caused by an imbalance of normal excitatory and inhibitory forces in the brain. Antiepileptic drug therapy has been directed primarily toward reducing excitability through blockage of voltage-gated Na + or Ca 2+ channels, or increasing inhibition through enhancement of γ-aminobutyric acid currents. Prior to clinical studies, putative antiepileptic drugs are screened in animals, usually rodents. Maximal electrical shock, pentylenetetrazol, and kindling are typically used as non-mechanistic screens for antiseizure properties and the rotorod test for assessing acute toxicity. While antiseizure drug screening has been successful in bringing drugs to the market and improving our understanding of the pathophysiology of seizures, it should be emphasized that the vast majority of drug screening occurs in mature male rodents and involves models of seizures, not epilepsy. Effective drugs in acute seizures may not be effective in chronic models of epilepsy. Seizure type, clinical and electroencephalographic phenotype, syndrome, and etiology are often quite different in children with epilepsy than adults. Despite these age-related unique features, drugs used in children are generally the same as used in adults. As awareness of the unique features of seizures during development increases, it is anticipated that more drug screening in the immature animal will occur.

show abstract

Section: Recurrent Seizuressupporting

confidence: 90%

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

Holmes¹,

Zhao²

2008

Pediatric Neurology

View full text Add to dashboard Cite

show abstract

“…In the infant Levine rat blood flow is dramaticallv sant (39). Seizures may aggravate cerebral damage induced by asphyxia (40,41). The effective anticonvulsant dose in rats is similar to that used in this study where the flunarizine-treated rats had significantly less posthypoxic fitting than the controls.…”

Section: Discussionsupporting

confidence: 52%

The Neuroprotective Actions of a Calcium Channel Antagonist, Flunarizine, in the Infant Rat

et al. 1989

View full text Add to dashboard Cite

ABSTRACT. One postulated final common pathway lead- MATERIALS AND METHODSing to neuronal death after hypoxic-ischemic insults is an increase in intracellular calcium concentrations. We exExperimental preparation. The 21-d-old Wistar rats were anamined the effect of pretreatment with flunarizine, a ,,+ aesthetised with a 2% halothane/02 mixture. In each rat one cium channel antagonist known to pass the blood brain carotid artery was exposed and ligated with 6.0 silk sutures. The barrier, on the behavioral and histologic changes after an rats were removed from anaesthesia and then received, by intrahypoxic-ischemic insult in the infant rat. The 21-d-old rats peritoneal injection, either flunarizine (Janssen Pharmaceutica, were subjected to unilateral carotid ligation, then to 2 h of Beers% Belgium), 30 mg/kg or an equal volume of the diluent, hypoxia. They were pretreated with either flunarizine (30 10% ethanol, 1.5 ml/kg, given in equally divided doses. The first mg,kg, intraperitoneally) or with an equal volume of dose was given immediately after surgery, the second immedidiluent. After 5 days of observation they were killed for ately before the hypoxia2 later. histology. Acute behavioral abnormalities wereEach rat was next subjected to an h~~o x i c environment of 8% in more controls than treatment animals, 52 vs 11% ( p < 0 2 and 2% COz [to prevent hypocapnia induced vasospasm 0.002). Cerebral injury was almost entirely confined to the (2411, maintained at 37" C, for 120 min. The pups were then ligated side and was significantly worse in the control rats. returned to their cages, with their litter mates. Daily after the ~~1 1 thickness cortical infarction was noted in 56% of hypoxia each rat was behaviorally tested by a blind, independent controls (n = 27) vs 4% of flunarizine-treated rats (n = observer (LB), who scored each for the presence of five possible 24), (p < O.OO1). Mean and maximum damage scores for abnormalities: fits, absence of startle response, abnormal turning, all areas assessed including cortex, corpus striaturn, tllal-impaired righting, and impaired response to tail pinch (23, 25). amus, amygdala, and h~ppocampus were improved mark-On the day of death a further scoring for residual abnormalities edly in treatment rats (p < 0 . 0 0~) . These observations was made. The presence of definite unilateral weakness was confirm that flunarizine, when given prophylactically, has scored as 2, whereas other behavioral problems such as excessive a neuroprotective effect against hypoxic-ischemic injury in or reduced activity or persistent piloerection were scored as 1. the developing brain. (Pediatr Res 25:573-576). Death was by the injection of pentobarbital. These experiments were approved by the Animal Ethical Committee of the University of Auckland. Pilot study. This study included the two main groups. 1 ) Flunarizine pretreated, with ligation and hypoxia, the treatment Perinatal hypoxic-ischemic encephalopathy is associated with group (n = 5). 2) Ethanol pretreated, with ligation and hypoxia, a signi...

show abstract

“…Human cerebellar DNA content increases at least fourfold between birth and 1 year of age (31), and the cerebellar external granular layer of cells is present long after that. This layer gives rise largely t o neurons in the rat, mouse, cat, dog, chick, and probably in man (28), and attains its maximum cell number in man at some stage after birth (24). Cerebral DNA in the human neonate increases threefold in the 1st year of life (31), but there is less evidence for postnatal neuronal mitosis.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid Effect upon Thymidine Kinase in the Developing Cerebellum

Weichsel

1974

Pediatr Res

View full text Add to dashboard Cite

ExtractForty-nine litters of eight Sprague-Dawley rat pups were divided into four pups treated with 0.6 mg hydrocortisone acetate on the day of bir.th and four littermate controls. The mean body weight, cerebellar weight, and cerebellar DNA were significantly depressed in treated pups by 3 days of age, with all three of these measurements of growth increasing. in rate around 9 days of age, but remaining well below control values throughout 15 days of age. Body weight and cerebellar DNA were maximally depressed at age 12 days (37.7% and 46.6% of control values, respectively), and cerebellar wet weight was maximally depressed to 5 1.5% of the control value at 9 days of age. The activity of thymidine kinase, a salvage pathway enzyme for pyrimidine biosynthesis, was found t o be depressed t o 80.2% and 74.1% of the control value at 3 and 6 days of age, respectively and elevated to 134% and 158% over control values at ages 12 and 15 days. The depression of thymidine kinase activity by hydrocortisone at ages 3 and 6 days followed by the overshoot of enzyme activity after steroid-induced growth suppression had subsided suggests that the thymidine kinase may be considered as having an essential regulatory function in the rate of DNA synthesis in developing brain. SpeculationExtrapolation of these hormone-enzyme relations in developing rat cerebellum t o the clinical use of glucocorticoids in acceleration of lung maturation in human premature infants suggests the possibility that concomitant effects of the steroid may be detrimental t o the development of brain areas which undergo cell replication at the time the drug is administered.Glucocorticosteroids have been used therapeutically for the last few years in diseases of early childhood including myoclonic seizures of childhood (9) and hypoglycemia (22). More recently, glucocorticoids have been used in animal experimentation in studies on maturation of the lung in lambs and rabbits. Liggins and Howie (18) showed that when labor can be delayed a t least 24 hr in unplanned deliveries of infants under 32 weeks gestation, infusion of P-methasone into the mother can prevent respiratory distress syndrome in the infant. These studies, which reflect the ability of glucocorticoids to accelerate lung maturation and prevent the consequences of surfactant deficiency, will undoubtedly lead t o a greater volume of clinical experimentation regarding the use of glucocorticoids in mothers when premature delivery threatens. Although these recent clinical studies appear promising, little attention has been paid t o possible deleterious effects of steroids on fetal organs other than the lung. Avery (4) has pointed out the possibility of permanent neurologic damage as a consequence of steroid therapy in the developing fetus, but more recently described profound effects of glucocorticoids upon brain development have not heretofore been emphasized in the pediatric literature. The studies of Balhzs and Cotterrell (5) and Cotterrell e t al. (12) on the effects of corticosteroids on the maturat...

show abstract

Vulnerability of Developing Rat Brain to Electroconvulsive Seizures

Cited by 164 publications

References 43 publications

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

The Neuroprotective Actions of a Calcium Channel Antagonist, Flunarizine, in the Infant Rat

Glucocorticoid Effect upon Thymidine Kinase in the Developing Cerebellum

Contact Info

Product

Resources

About