A novel reproducible model of neonatal stroke in mice: Comparison with a hypoxia–ischemia model
| Autor: | Akihiko Taguchi, Masahiro Tsuji, Tomoaki Ikeda, Tomohiro Matsuyama, Yukiko Kasahara, Makiko Ohshima |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Time Factors Cerebral palsy Mice Epilepsy Developmental Neuroscience medicine.artery medicine Animals cardiovascular diseases Stroke Neonatal stroke Analysis of Variance Neonatal encephalopathy business.industry Body Weight Brain Infarction Middle Cerebral Artery Stroke volume medicine.disease Disease Models Animal Animals Newborn Neurology Cerebral blood flow Motor Skills Regional Blood Flow Rotarod Performance Test Anesthesia Hypoxia-Ischemia Brain Middle cerebral artery Exploratory Behavior Female business |
| Zdroj: | Experimental Neurology. 247:218-225 |
| ISSN: | 0014-4886 |
| Popis: | Neonatal stroke occurs in 1/4000 live births and leaves life-long neurological impairments, such as cerebral palsy and epilepsy. Currently, the rodent models of neonatal stroke that are available exhibit significant inter-animal variability, which makes it difficult to accurately assess the mechanisms of brain injury and the efficacy of candidate treatments. We aimed to introduce a novel, highly reproducible model of stroke, middle cerebral artery occlusion (MCAO), in immature mice, and to evaluate the reproducibility of this model compared with a conventional hypoxia-ischemia (HI) model. Postnatal day 12 CB-17 mice underwent left MCAO by direct electrocoagulation. The MCAO model exhibited excellent long-term survival; 85% up to 8 weeks after the insult. Infarct was evident in every animal with MCAO (n=27) and was confined to the cortex, with the exception of some mild thalamic injury. While the % stroke volume 48 h after the insult was consistent in the MCAO group, range: 17.8-30.4% (minimum-maximum), it was substantially less consistent in the HI group, range: 3.0-70.1%. This contrasting variability between the two models was also evident in the cerebral blood flow, 24h after the insult, and in the ipsilateral hemispheric volume, as assessed at 8 weeks after the insult. Mice with MCAO exhibited significant neurofunctional deficits in the rotarod and open-field tests. Preclinical studies for neonatal stroke could become more reliable using this model, with even a potential reduction in the number of pups required for statistical significance. The contrasting variability between the two models may provide insights into the factors that contribute to inter-animal variability in brain injury. |
| Databáze: | OpenAIRE |
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