Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke
Autor: | Samantha Hamilton, Raymond C.B. Wong, Emmanuel Pinteaux, Danielle N. Edwards, Justin F. Fraser, Michael E. Maniskas, Ivana Rajkovic, Kathleen E Salmeron, Gregory J. Bix, Abir A Rahman, Amanda L Trout |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
Neurology Hemodynamics LG3 lcsh:RC346-429 Brain Ischemia Brain ischemia Mice 0302 clinical medicine Interleukin-1alpha Occlusion Common carotid artery Interleukin 1 alpha Stroke Neurons 0303 health sciences Behavior Animal General Neuroscience Brain Neuroprotection 3. Good health Neuroprotective Agents Cardiology medicine.symptom Therapeutic medicine.medical_specialty Immunology Inflammation Mouse model 03 medical and health sciences Cellular and Molecular Neuroscience Internal medicine medicine.artery Neurorepair medicine Animals lcsh:Neurology. Diseases of the nervous system 030304 developmental biology business.industry Research Recovery of Function medicine.disease Perlecan Disease Models Animal Angiogenesis business 030217 neurology & neurosurgery |
Zdroj: | Salmeron, K E, Maniskas, M E, Edwards, D N, Wong, R, Rajkovic, I, Trout, A, Rahman, A A, Hamilton, S, Fraser, J F, Pinteaux, E & Bix, G J 2019, ' Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke ', Journal of Neuroinflammation, vol. 16, no. 1 . https://doi.org/10.1186/s12974-019-1599-9 Journal of Neuroinflammation Journal of Neuroinflammation, Vol 16, Iss 1, Pp 1-14 (2019) |
Popis: | Background Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et al., J Cereb Blood Flow Metab 37:3531–3543, 2017; Hill et al., Lancet Neurol 11:942–950, 2012; Amaro et al., Stroke 47:2874–2876, 2016). Methods Transient stroke was induced in mice via one of two methods. One group of mice were subjected to tandem ipsilateral common carotid artery and middle cerebral artery occlusion, while another group underwent the filament-based middle cerebral artery occlusion. We have recently developed an animal model of intra-arterial (IA) drug administration after recanalization (Maniskas et al., J Neurosci Met 240:22–27, 2015). Sub groups of the mice were treated with either saline or Il-1α, wherein the drug was administered either acutely (immediately after surgery) or subacutely (on the third day after stroke). This was followed by behavioral and histological analyses. Results We now show in the above-mentioned mouse stroke models (transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery occlusion (MCA) occlusion, MCA suture occlusion) that IL-1α is neuroprotective when acutely given either intravenously (IV) or IA at low sub-pathologic doses. Furthermore, while IV administration induces transient hemodynamic side effects without affecting systemic markers of inflammation, IA delivery further improves overall outcomes while eliminating these side effects. Additionally, we show that delayed/subacute IV IL-1α administration ameliorates functional deficit and promotes neurorepair. Conclusions Taken together, our present study suggests for the first time that IL-1α could, unexpectedly, be an effective ischemic stroke therapy with a broad therapeutic window. |
Databáze: | OpenAIRE |
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