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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.00942

Central application of Aliskiren, a renin inhibitor, improves outcome after experimental stroke independent of its blood pressure lowering effect

  • 1Institute for Stroke and Dementia Research (ISD), Germany
  • 2Department of Physiology, Ardabil University of Medical Sciences, Iran
  • 3Department of Neurosurgery, University Hospital Munich, Germany
  • 4Munich Cluster of Systems Neurology, Germany
  • 5Faculty of Chemistry and Pharmacy, Ludwig-Maximilians-University Munich, Germany
  • 6Institute of Pharmacology and Clinical Pharmacy, Philipps-University of Marburg, Germany

Epidemiological studies suggest that pharmacological reduction of systemic hypertension lowers incidence and severity of stroke. However, whether the reduction of blood pressure per se or the compounds used to reduce hypertension are responsible for this effect received little attention. In the current study we therefore aimed to investigate whether Aliskiren, a renin-inhibitor used to treat arterial hypertension, may improve outcome in a mouse model of ischemic stroke when applied centrally and in a dose not affecting blood pressure.
Male C57BL/6 mice received 0.6, 2.0, or 6.0 µg Aliskiren or vehicle by intracerebroventricular injection as a pre-treatment and were then subjected to 60 min of middle cerebral artery occlusion (MCAo). Infarct volume, brain edema formation, mortality, antioxidant effects, and functional outcome were assessed up to seven days after MCAo.
Central administration of Aliskiren (0.6 or 2.0 µg) had no effect on systemic blood pressure but significantly reduced infarct volume and brain edema formation, blunted mortality, and improved neurological outcome up to one week after MCAo.
Due to the central and prophylactic administration of the compound, we cannot make any conclusions about the potency of Aliskiren for acute stroke treatment, however, our study clearly demonstrates, that in addition to lowering blood pressure Aliskiren seems to have a direct neuroprotective effect. Hence, renin-inhibitors may be an effective addition to prophylactic treatment regimens in stroke patients.

Keywords: Brain Edema, Hypertension, Neuroprotection, Stroke, acute stroke, experimental, Focal ischemia

Received: 10 Feb 2019; Accepted: 14 Aug 2019.

Copyright: © 2019 Panahpour, Terpolilli, Schaffert, Culmsee and Plesnila. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Nikolaus Plesnila, Institute for Stroke and Dementia Research (ISD), Munich, 81377, Bavaria, Germany, nikolaus.plesnila@med.uni-muenchen.de