Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice

Peng, Junwen; Li, Ran; Arora, Neha; Lau, Marcus; Lim, Stellar; Wu, Chenggang; Eubanks, James H.; Zhang, Liang

doi:10.1016/j.eplepsyres.2015.01.009

Cited by 11 publications

(13 citation statements)

References 29 publications

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“…Brain histological assessments were conducted as previously described [ 38 , 47 , 61 – 62 ]. Animals were anesthetized with an intra-peritoneal injection of sodium pentobarbital (70 mg/kg) and transcardially perfused with 10% neutral buffered formalin solution.…”

Section: Methodsmentioning

confidence: 99%

Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments

Wang

Peng

et al. 2015

PLoS ONE

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Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic) and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI) model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min). Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG) monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex) with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute mortality in aging mice following severe brain ischemia and that early anticonvulsive treatment may prevent seizure genesis and improve overall outcomes.

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Section: Methodsmentioning

confidence: 99%

Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments

Wang

Peng

et al. 2015

PLoS ONE

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“…Postnatal day 7 C57BL/6 mice were treated with the HI protocol and then monitored with video and EEG at 3 months. Two of 23 treated mice were reported to have seizures of class 4 or higher (Peng et al, 2015).…”

Section: Recurrent Seizuresmentioning

confidence: 98%

“…Behavioral and electrographic activity during and immediately after the hypoxic episode has been characterized (Cuaycong et al, Peng et al (2015) 2011; Sampath et al, 2014). In a recent study characterizing HIinduced seizures in P7 rat pups, the day before HI, rats were implanted with silver electrodes while under isoflurane anesthesia.…”

Section: Eeg Monitoring Of Himentioning

confidence: 99%

Models of hypoxia and ischemia-induced seizures

Sun

Juul

Jensen

2016

Journal of Neuroscience Methods

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“…But more importantly, the study showed that if the perinatal HI insult did not result in an infarct injury, no epilepsy was detected in such rats even with 1 year of continuous monitoring. One similar study using neonatal HI model has recently shown that brain injury can develop at later stages, 11 months post HI insult ( 53 ). Motor seizures were identified only in animals with cystic infarct, but none in the animals without infarct.…”

Section: Etiologymentioning

confidence: 99%

Neonatal Seizures: Impact on Neurodevelopmental Outcomes

Kang

Kadam

2015

Front. Pediatr.

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Neonatal period is the most vulnerable time for the occurrence of seizures, and neonatal seizures often pose a clinical challenge both for their acute management and frequency of associated long-term co-morbidities. Etiologies of neonatal seizures are known to play a primary role in the anti-epileptic drug responsiveness and the long-term sequelae. Recent studies have suggested that burden of acute recurrent seizures in neonates may also impact chronic outcomes independent of the etiology. However, not many studies, either clinical or pre-clinical, have addressed the long-term outcomes of neonatal seizures in an etiology-specific manner. In this review, we briefly review the available clinical and pre-clinical research for long-term outcomes following neonatal seizures. As the most frequent cause of acquired neonatal seizures, we focus on the studies evaluating long-term effects of HIE-seizures with the goal to evaluate (1) what parameters evaluated during acute stages of neonatal seizures can reliably be used to predict long-term outcomes? and (2) what available clinical and pre-clinical data are available help determine importance of etiology vs. seizure burdens in long-term sequelae.

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Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice

Cited by 11 publications

References 29 publications

Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments

Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments

Models of hypoxia and ischemia-induced seizures

Neonatal Seizures: Impact on Neurodevelopmental Outcomes

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