title: Different response to antiepileptic drugs according to the type of epileptic events in a neonatal ischemia-reperfusion model.
abstract: Perinatal arterial stroke is the most frequent form of cerebral infarction in children. Neonatal seizures are the most frequent symptom during the neonatal period. The current management of perinatal stroke is based on supportive care. It is currently unknown if treatment of the seizures modifies the outcome, and no clinical studies have focused on seizures during neonatal stroke. We studied the effect of phenobarbital and levetiracetam on an ischemic-reperfusion stroke model in P7 rats using prolonged electroencephalographic recordings and a histologic analysis of the brain (24h after injury). The following two types of epileptic events were observed: 1) bursts of high amplitude spikes during ischemia and the first hours of reperfusion and 2) organized seizures consisting in discharges of a 1-2Hz spike-and-wave. Both phenobarbital and levetiracetam decreased the total duration of the bursts of high amplitude spikes. Phenobarbital also delayed the start of seizures without changing the total duration of epileptic discharges. The markedly limited efficacy of the antiepileptic drugs studied in our neonatal stroke rat model is frequently observed in human neonatal seizures. Both drugs did not modify the stroke volume, which suggests that the modification of the quantity of bursts of high amplitude spikes does not influence the infarct size. In the absence of a reduction in seizure burden by the antiepileptic drugs, we increased the seizure burden and stroke volume by combining our neonatal stroke model with a lithium-pilocarpine-induced status epilepticus. Our data suggest that the reduction of burst of spikes did not influence the stroke volume. The presence of organized seizure with a pattern close to what is observed in human newborns seems related to the presence of the infarct. Further research is required to determine the relationship between seizure burden and infarct volume.
authors.affiliation: PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Morin
authors.affiliation: PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Enderlin
authors.affiliation: PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; UPMC, Paris Universitas, AP-HP, Hôpital Armand Trousseau, Service de Réanimation pédiatrique, Paris, France.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Leger
authors.affiliation: PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Perrotte
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, INSERM, U965, 75010 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnin
authors.affiliation: PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Dupuis
authors.affiliation: PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, AP-HP Service de Réanimation Néonatale, Hôpital Robert Debré, 75019 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Baud
authors.affiliation: PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Charriaut-Marlangue
authors.affiliation: PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Robert Debré, Service de Neurologie Pédiatrique, 75019 Paris, France. Electronic address: stephane.auvin@inserm.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Auvin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D000077287:Levetiracetam; D018020:Lithium Compounds; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D010862:Pilocarpine; D010889:Piracetam / Q000031:analogs & derivatives / Q000494:pharmacology; D011897:Random Allocation; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants; D018020:Lithium Compounds; D010862:Pilocarpine; D000077287:Levetiracetam; D010634:Phenobarbital; D010889:Piracetam
keywords: Levetiracetam; Phenobarbital; Rat; Seizure; Stroke