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Immunohistochemical evidence of tissue hypoxia and astrogliosis in the rostral ventrolateral medulla of spontaneously hypertensive rats

Turlejski, T; Humoud, I; Desai, R; Smith, KJ; Marina, N; (2016) Immunohistochemical evidence of tissue hypoxia and astrogliosis in the rostral ventrolateral medulla of spontaneously hypertensive rats. Brain Research , 1650 pp. 178-183. 10.1016/j.brainres.2016.09.012. Green open access

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Abstract

Increased activity of the sympathetic nervous system has been highlighted as a key factor that contributes to the development and maintenance of arterial hypertension. However, the factors that precipitate sustained increases in sympathetic activity remain poorly understood. Resting tissue oxygen partial pressure (PtO2) in the brainstem of anesthetized spontaneously hypertensive rats (SHRs) has been shown to be lower than in normotensive rats despite normal levels of arterial PO2. A hypoxic environment in the brainstem has been postulated to activate astroglial signalling mechanisms in the rostral ventrolateral medulla (RVLM) which in turn increase the excitability of presympathetic neuronal networks. In this study, we assessed the expression of indirect markers of tissue hypoxia and astroglial cell activation in the RVLM of SHRs and age-matched normotensive Wistar rats. Immunohistochemical labelling for hypoxia-induced factor-1α (HIF-1α) and bound pimonidazole adducts revealed the presence of tissue hypoxia in the RVLM of SHRs. Double immunostaining showed co-localization of bound pimonidazole labelling in putative presympathetic C1 neurons and in astroglial cells. Quantification of glial fibrillary acidic protein (GFAP) immunofluorescence showed relatively higher number of astrocytes and increased GFAP mean grey value density, whilst semi-quantitative analysis of skeletonized GFAP-immunoreactive processes revealed greater % area covered by astrocytic processes in the RVLM of adult SHRs. In conclusion, the morphological findings of tissue hypoxia and astrogliosis within brainstem presympathetic neuronal networks in the SHR support previous observations, showing that low brainstem PtO2 and increased astroglial signalling in the RVLM play an important role in pathological sympathoexcitation associated with the development of arterial hypertension.

Type: Article
Title: Immunohistochemical evidence of tissue hypoxia and astrogliosis in the rostral ventrolateral medulla of spontaneously hypertensive rats
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.brainres.2016.09.012
Publisher version: http://dx.doi.org/10.1016/j.brainres.2016.09.012
Language: English
Additional information: © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Hypoxia, Arterial hypertension, Sympathetic nervous system, Astrogliosis, SYMPATHETIC-NERVOUS-SYSTEM, NOREPINEPHRINE TURNOVER, BLOOD-PRESSURE, CONTRIBUTES, MECHANISMS, RESISTANCE, INFARCTION, DISEASE, Hypoxia, Arterial hypertension, Sympathetic nervous system, Astrogliosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1516682
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