Long‐term outcome in a noninvasive rat model of birth asphyxia with neonatal seizures: Cognitive impairment, anxiety, epilepsy, and structural brain alterations
| Autor: | Kerstin Römermann, Marie Johne, Björn Gailus, Lisa Welzel, Kai Kaila, Hannah Naundorf, Wolfgang Löscher |
|---|---|
| Přispěvatelé: | Molecular and Integrative Biosciences Research Programme, Neuroscience Center, Kai Kaila / Principal Investigator, Laboratory of Neurobiology |
| Rok vydání: | 2021 |
| Předmět: |
Male
Encephalopathy Hippocampus HYPERACTIVITY Brain damage Anxiety Electroencephalography Asphyxia 03 medical and health sciences Epilepsy AGE 0302 clinical medicine Seizures 030225 pediatrics INJURY medicine Animals Humans Cognitive Dysfunction Hypoxia Asphyxia Neonatorum medicine.diagnostic_test business.industry MEMORY Infant Newborn 3112 Neurosciences Brain ENCEPHALOPATHY Hypoxia (medical) medicine.disease ATTENTION-DEFICIT Rats 3. Good health Animals Newborn Neurology Anesthesia Hypoxia-Ischemia Brain HIPPOCAMPUS Female SYNAPTIC POTENTIATION Neurology (clinical) HYPOXIA-ISCHEMIA medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Epilepsia. 62:2826-2844 |
| ISSN: | 1528-1167 0013-9580 |
| Popis: | Objective: Birth asphyxia is a major cause of hypoxic-ischemic encephalopathy (HIE) in neonates and often associated with mortality, neonatal seizures, brain damage, and later life motor, cognitive, and behavioral impairments and epilepsy. Preclinical studies on rodent models are needed to develop more effective therapies for preventing HIE and its consequences. Thus far, the most popular rodent models have used either exposure of intact animals to hypoxia-only, or a combination of hypoxia and carotid occlusion, for the induction of neonatal seizures and adverse outcomes. However, such models lack systemic hypercapnia, which is a fundamental constituent of birth asphyxia with major effects on neuronal excitability. Here, we use a recently developed noninvasive rat model of birth asphyxia with subsequent neonatal seizures to study later life adverse outcome. Methods: Intermittent asphyxia was induced for 30 min by exposing male and female postnatal day 11 rat pups to three 7 + 3-min cycles of 9% and 5% O-2 at constant 20% CO2. All pups exhibited convulsive seizures after asphyxia. A set of behavioral tests were performed systematically over 14 months following asphyxia, that is, a large part of the rat's life span. Video-electroencephalographic (EEG) monitoring was used to determine whether asphyxia led to the development of epilepsy. Finally, structural brain alterations were examined. Results: The animals showed impaired spatial learning and memory and increased anxiety when tested at an age of 3-14 months. Video-EEG at similar to 10 months showed an abundance of spontaneous seizures, which was paralleled by neurodegeneration in the hippocampus and thalamus, and by aberrant mossy fiber sprouting. Significance: The present model of birth asphyxia recapitulates several of the later life consequences associated with human HIE. This model thus allows evaluation of the efficacy of novel therapies designed to prevent HIE and seizures following asphyxia, and of how such therapies might alleviate long-term adverse consequences. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text