eprintid: 1516682
rev_number: 33
eprint_status: archive
userid: 608
dir: disk0/01/51/66/82
datestamp: 2016-09-24 22:48:59
lastmod: 2021-10-10 23:00:06
status_changed: 2016-09-24 22:48:59
type: article
metadata_visibility: show
creators_name: Turlejski, T
creators_name: Humoud, I
creators_name: Desai, R
creators_name: Smith, KJ
creators_name: Marina, N
title: Immunohistochemical evidence of tissue hypoxia and astrogliosis in the rostral ventrolateral medulla of spontaneously hypertensive rats
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F87
divisions: C10
divisions: D17
divisions: FI5
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
note: © 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/).
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.
date: 2016-11-01
date_type: published
publisher: ELSEVIER SCIENCE BV
official_url: http://dx.doi.org/10.1016/j.brainres.2016.09.012
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_manual
elements_id: 1159348
doi: 10.1016/j.brainres.2016.09.012
language_elements: ENG
lyricists_name: Desai, Roshni
lyricists_name: Marina-Gonzalez, Nephtali
lyricists_name: Smith, Kenneth
lyricists_id: RDESA67
lyricists_id: NGMAR80
lyricists_id: KJSMI17
full_text_status: public
publication: Brain Research
volume: 1650
pagerange: 178-183
pages: 6
issn: 0006-8993
citation:        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 <https://doi.org/10.1016/j.brainres.2016.09.012>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1516682/1/1-s2.0-S0006899316306205-main.pdf