Mattis Bertlich1, Friedrich Ihler2, Bernhard G Weiss2, Saskia Freytag3, Michael Strupp4, Mark Jakob2, Martin Canis2. 1. Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. Electronic address: Mattis.Bertlich@med.uni-goettingen.de. 2. Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. 3. Population Health and Immunity Division, Walter and Eliza Hall Institute, 1G Royal Parade, 3052 Parkville, Australia; Department of Medical Biology, University of Melbourne, 1G Royal Parade, 3052, Parkville, Australia. 4. Department of Neurology, Munich University Hospital, Marchioninistr. 15, 81377 Munich, Germany; German Center for Vertigo and Balance Disorders, Munich University Hospital, Marchioninistr. 15, 81377 Munich, Germany.
Abstract
AIMS: Betahistine is a histamine analogue that is used for the treatment of Menière's disease. Animal studies showed that it increases local blood flow in the stria vascularis. In terms of its mode of action, recent studies have prompted discussion of whether betahistine actively affects cochlear microcirculation by dilations of pericytes or of precapillary arterioles or by mere downstream effects. Hence, we investigated the effects of betahistine on cochlear capillary pericytes and precapillary arterioles. MAIN METHODS: The stria vascularis was visualized in 12 guinea pigs by in vivo fluorescence microscopy. In these, 152 pericytes were stained and local diameter at sites of pericyte somas and downstream controls as well as intravascular blood flow were measured before and after betahistine application. Moreover, in two guinea pigs the precapillary arterioles were visualized by 2-photon-microscopy before and after betahistine application. KEY FINDINGS: There was no significant change in capillary diameter at sites of pericyte somas after betahistine application compared to controls, baseline or downstream controls, even though cochlear blood flow increased significantly. The two-photon measurements indicated an active dilation of precapillary arterioles. SIGNIFICANCE: Since we found no evidence that betahistine affects cochlear microcirculation by cochlear pericytes, its main mode of action is evidently active dilation of pre-capillary arterioles. These findings are in line with similar effects reported in the central nervous system and indicate an active effect on cochlear microcirculation.
AIMS: Betahistine is a histamine analogue that is used for the treatment of Menière's disease. Animal studies showed that it increases local blood flow in the stria vascularis. In terms of its mode of action, recent studies have prompted discussion of whether betahistine actively affects cochlear microcirculation by dilations of pericytes or of precapillary arterioles or by mere downstream effects. Hence, we investigated the effects of betahistine on cochlear capillary pericytes and precapillary arterioles. MAIN METHODS: The stria vascularis was visualized in 12 guinea pigs by in vivo fluorescence microscopy. In these, 152 pericytes were stained and local diameter at sites of pericyte somas and downstream controls as well as intravascular blood flow were measured before and after betahistine application. Moreover, in two guinea pigs the precapillary arterioles were visualized by 2-photon-microscopy before and after betahistine application. KEY FINDINGS: There was no significant change in capillary diameter at sites of pericyte somas after betahistine application compared to controls, baseline or downstream controls, even though cochlear blood flow increased significantly. The two-photon measurements indicated an active dilation of precapillary arterioles. SIGNIFICANCE: Since we found no evidence that betahistine affects cochlear microcirculation by cochlear pericytes, its main mode of action is evidently active dilation of pre-capillary arterioles. These findings are in line with similar effects reported in the central nervous system and indicate an active effect on cochlear microcirculation.