Neuroprotection by Exogenous and Endogenous Neuregulin-1 in Mouse Models of Focal Ischemic Stroke
| Autor: | Byron D. Ford, Jessica Noll, Timothy J. Distel, Gregory D. Ford, Yonggang Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Middle Cerebral Artery Aging Endogeny Pharmacology Inbred C57BL Transgenic Brain ischemia Mice 0302 clinical medicine Ischemia Stroke erbB receptor biology Infarction Middle Cerebral Artery General Medicine Neuroprotection Neuroprotective Agents Infarction 5.1 Pharmaceuticals Neurological Knockout mouse Cognitive Sciences Female Development of treatments and therapeutic interventions Cell death Heterozygote Neuregulin-1 03 medical and health sciences Cellular and Molecular Neuroscience medicine Animals cardiovascular diseases Neuregulin 1 Inflammation Neurology & Neurosurgery business.industry Neurosciences medicine.disease Brain Disorders Mice Inbred C57BL 030104 developmental biology biology.protein NeuN business 030217 neurology & neurosurgery |
| Zdroj: | Journal of molecular neuroscience : MN, vol 69, iss 2 |
| ISSN: | 1559-1166 |
| Popis: | Identifying novel neuroprotectants that can halt or reverse the neurological effects of stroke is of interest to both clinicians and scientists. We and others previously showed the pre-clinical neuroprotective efficacy of neuregulin-1 (NRG-1) in rats following focal brain ischemia. In this study, we examined neuroprotection by exogenous and endogenous NRG-1 using a mouse model of ischemic stroke. C57BL6 mice were subjected to middle cerebral artery occlusion (MCAO) followed by reperfusion. NRG-1 or vehicle was infused intra-arterially (i.a.) or intravenously (i.v.) after MCAO and before the onset of reperfusion. NRG-1 treatment (16μg/kg; i.a.) reduced cerebral cortical infarct volume by 72% in mice when delivered post-ischemia. NRG-1 also inhibited neuronal injury as measured by Fluoro Jade B labeling and rescued NeuN immunoreactivity in neurons. Neuroprotection by NRG-1 was also observed in mice when administered i.v. (100μg/kg) in both male and female mice. We investigated whether endogenous NRG-1 was neuroprotective using male and female heterozygous NRG-1 knockout mice (NRG-1+/-) compared with wild-type mice (WT) littermates. NRG-1+/- and WT mice were subjected to MCAO for 45min, and infarct size was measured 24h following MCAO. NRG-1+/- mice displayed a sixfold increase in cortical infarct size compared with WT mice. These results demonstrate that NRG-1 treatment mitigates neuronal damage following cerebral ischemia. We further showed that reduced endogenous NRG-1 results in exacerbated neuronal injury in vivo. These findings suggest that NRG-1 represents a promising therapy to treat stroke in human patients. |
| Databáze: | OpenAIRE |
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