Sexual dimorphism in the cerebrovascular network: Brain MRI shows lower arterial density in women.
arterial density
dementia
sexual dimorphism
stroke
Journal
Journal of neuroimaging : official journal of the American Society of Neuroimaging
ISSN: 1552-6569
Titre abrégé: J Neuroimaging
Pays: United States
ID NLM: 9102705
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
11
11
2021
received:
10
08
2021
accepted:
12
11
2021
pubmed:
4
12
2021
medline:
22
3
2022
entrez:
3
12
2021
Statut:
ppublish
Résumé
Accumulating evidence suggests that there is a sexual dimorphism in brain health, with women exhibiting greater disability following strokes of comparable size and having a higher prevalence of cognitive impairment later in life. Despite the critical implication of the cerebrovascular architecture in brain perfusion and brain health, it remains unclear whether structural differences in vessel density exist across the sexes. In this study, we used high-density MRI imaging to characterize the intracerebral arterial and venous density of 28 (14 women) sex-matched healthy young volunteers in vivo. Using an in-house vessel segmentation algorithm, we quantified and compared these vascular features across the cortical and subcortical deep gray matter, white matter, and periventricular white matter. We found that, on average, women have reduced intracerebral arterial density in comparison to men (F 2.34 ± 0.48%, M 2.67 ± 0.39%; p<.05). This difference was most pronounced in the subcortical deep gray matter (F 1.78 ± 0.53%, M 2.38 ± 0.82%; p<.05) and periventricular white matter (F 0.68 ± 0.15%, M 1.14 ± 0.33%; p<.0005), indicating a potential sex-specific vulnerability to hypoperfusion in areas critical to core cerebral functions. In contrast, venous density did not exhibit a significant difference between sexes. While this research remains exploratory, it raises important pathophysiological considerations for brain health, adverse cerebrovascular events, and dementia across the sexes. Our findings also highlight the need to take into account sex differences when investigating cerebral characteristics in humans.
Sections du résumé
BACKGROUND AND PURPOSE
Accumulating evidence suggests that there is a sexual dimorphism in brain health, with women exhibiting greater disability following strokes of comparable size and having a higher prevalence of cognitive impairment later in life. Despite the critical implication of the cerebrovascular architecture in brain perfusion and brain health, it remains unclear whether structural differences in vessel density exist across the sexes.
METHODS
In this study, we used high-density MRI imaging to characterize the intracerebral arterial and venous density of 28 (14 women) sex-matched healthy young volunteers in vivo. Using an in-house vessel segmentation algorithm, we quantified and compared these vascular features across the cortical and subcortical deep gray matter, white matter, and periventricular white matter.
RESULTS
We found that, on average, women have reduced intracerebral arterial density in comparison to men (F 2.34 ± 0.48%, M 2.67 ± 0.39%; p<.05). This difference was most pronounced in the subcortical deep gray matter (F 1.78 ± 0.53%, M 2.38 ± 0.82%; p<.05) and periventricular white matter (F 0.68 ± 0.15%, M 1.14 ± 0.33%; p<.0005), indicating a potential sex-specific vulnerability to hypoperfusion in areas critical to core cerebral functions. In contrast, venous density did not exhibit a significant difference between sexes.
CONCLUSIONS
While this research remains exploratory, it raises important pathophysiological considerations for brain health, adverse cerebrovascular events, and dementia across the sexes. Our findings also highlight the need to take into account sex differences when investigating cerebral characteristics in humans.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
337-344Informations de copyright
© 2021 American Society of Neuroimaging.
Références
Weber CM, Clyne AM. Sex differences in the blood-brain barrier and neurodegenerative diseases. APL Bioeng 2021;5011509.
Seshadri S, Beiser A, Kelly-Hayes M, Carlos, SK, Rhoda, A, and William, BK, et al. The lifetime risk of stroke: estimates from the Framingham Study. Stroke 2006;37:345-50.
Petrea RE, Beiser AS, Seshadri S, Margaret, KH, Carlos, SK, and Philip, AW. Gender differences in stroke incidence and poststroke disability in the Framingham Heart Study. Stroke 2009;40:1032-7.
Appelros P, Stegmayr B, Terent A. Sex differences in stroke epidemiology: a systematic review. Stroke 2009;40:1082-90.
Roquer J, Rodríguez Campello A, Gomis M. Sex differences in first-ever acute stroke. Stroke 2003;34:1581-5.
Gao S, Hendrie HC, Hall KS, Hui S. The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta-analysis. Arch Gen Psychiatry 1998;55:809-15.
Viña J, Lloret A. Why women have more Alzheimer's disease than men: gender and mitochondrial toxicity of amyloid-β peptide. J Alzheimers Dis 2010;20:527-33.
Iturria-Medina Y, Sotero RC, Toussaint PJ, Mateos-Pe ́rez, JM, Evans, AC, and The Alzheimer’s Disease Neuroimaging Initiative. Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis. Nat Commun 2016;7:11934.
Sweeney MD, Kisler K, Montagne A, Toga AW, Zlokovic BV. The role of brain vasculature in neurodegenerative disorders. Nat Neurosci 2018;21:1318-31.
Binnewijzend MAA, Kuijer JPA, Benedictus MR, van der Flier, WM, Wink, AM, and Wattjes, MP, et al. Cerebral blood flow measured with 3D pseudocontinuous arterial spin-labeling MR imaging in Alzheimer disease and mild cognitive impairment: a marker for disease severity. Radiology 2013;267:221-30.
Iadecola C. The pathobiology of vascular dementia. Neuron 2013;80:844-66.
de la Torre JC. Are major dementias triggered by poor blood flow to the brain? Theoretical considerations. J Alzheimers Dis 2017;57:353-71.
Aanerud J, Borghammer P, Rodell A, Jónsdottir KY, Gjedde A. Sex differences of human cortical blood flow and energy metabolism. J Cereb Blood Flow Metab 2017;37:2433-40.
Liu Y, Zhu X, Feinberg D, Guenther, M, Gregori, J, and Weiner, MW, et al. Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics. Magn Reson Med 2012;68:912-22.
Matteis M, Troisi E, Monaldo BC, Caltagirone C, Silvestrini M. Age and sex differences in cerebral hemodynamics: a transcranial Doppler study. Stroke 1998;29:963-7.
Mosconi L, Berti V, Guyara-Quinn C, McHugh, P, Petrongolo, G, and Osorio, RS, et al. Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery. PLoS One 2017;12:e0185926.
Gorelick PB, Furie KL, Iadecola C, Smith, EE, Waddy, SP, and Lloyd-Jones, DM, et al. Defining optimal brain health in adults: a presidential advisory from the American Heart Association/American Stroke Association. Stroke 2017;48:e284-303.
Wang Y, Pan Y, Li H. What is brain health and why is it important? BMJ 2020;371:m3683.
Vigneau-Roy N, Bernier M, Descoteaux M, Whittingstall K. Regional variations in vascular density correlate with resting-state and task-evoked blood oxygen level-dependent signal amplitude. Hum Brain Mapp 2014;35:1906-20.
Bizeau A, Gilbert G, Bernier M, Huynh, MT, Bocti, C, and Descoteaux, M, et al. Stimulus-evoked changes in cerebral vessel diameter: a study in healthy humans. J Cereb Blood Flow Metab 2017;38:528-39.
Bernier M, Cunnane SC, Whittingstall K. The morphology of the human cerebrovascular system. Hum Brain Mapp 2018;39:4962-75.
Avants B, Tustison N, Song G. Advanced Normalization Tools (ANTS). Insight J 2009;1:1-35.
Cox RW. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 1996;29:162-73.
Provencher D, Bizeau A, Gilbert G, Bérubé-Lauzière Y, Whittingstall K. Structural impacts on the timing and amplitude of the negative BOLD response. Magn Reson Imaging 2018;45:34-42.
Lindekleiv HM, Valen-Sendstad K, Morgan MK, Mardal, KA, Faulder, K, and Magnus, JH, et al. Sex differences in intracranial arterial bifurcations. Gend Med 2010;7:149-55.
Schulz UGR, Rothwell PM. Sex differences in carotid bifurcation anatomy and the distribution of atherosclerotic plaque. Stroke 2001;32.1525-31.
Krejza J, Arkuszewski M, Kasner SE, Weigele, J, Ustymowicz, A, and Hurst, RW, et al. Carotid artery diameter in men and women and the relation to body and neck size. Stroke 2006;37:1103-5.
Minhas JS, Panerai RB, Robinson TG. Sex differences in cerebral haemodynamics across the physiological range of PaCO2. Physiol Meas 2018;39:105009.
Huxley VH, Kemp SS. Sex-specific characteristics of the microcirculation. Adv Exp Med Biol 2018;1065:307-28.
Chan MV, Bubb KJ, Noyce A, Villar, IC, Duchene, J, and Hobbs, AJ, et al. Distinct endothelial pathways underlie sexual dimorphism in vascular auto-regulation. Br J Pharmacol 2012;167:805-17.
Huang A, Sun D, Koller A, Kaley G. Gender difference in myogenic tone of rat arterioles is due to estrogen-induced, enhanced release of NO. Am J Physiol Circ Physiol 1997;272.H1804-9.
Ahnstedt H, Cao L, Krause DN, Warfvinge, K, Säveland, H, and Nilsson, OG, et al. Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries. PLoS One 2013;8:e62698.
Gonzales RJ, Bryant JM, Naik JS, Resta TC, Walker BR. Gender differences in mesenteric vasoconstrictor reactivity following chronic hypoxia. Microcirculation 2008;15.473-84.
Sieveking DP, Lim P, Chow RWY, Dunn, LL, Bao, S, and McGrath, KCY, et al. A sex-specific role for androgens in angiogenesis. J Exp Med 2010;207:345-52.
Ng MK, Quinn CM, McCrohon JA, Nakhla, S, Jessup, W, and Handelsman, DJ, et al. Androgens up-regulate atherosclerosis-related genes in macrophages from males but not females. J Am Coll Cardiol 2003;42.1306-13.
Death AK, McGrath KCY, Sader MA, Nakhla, S, Jessup, W, and Handelsman, DJ, et al. Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-κB-dependent pathway. Endocrinology 2004;145:1889-97.
Pan Y, Zhang H, Acharya AB, Patrick, PH, Oliver, D, and Morley, JE. Effect of testosterone on functional recovery in a castrate male rat stroke model. Brain Res 2005;1043:195-204.
Bachmann J, Feldmer M, Ganten U, Stock G, Ganten D. Sexual dimorphism of blood pressure: possible role of the renin-angiotensin system. J Steroid Biochem Mol Biol 1991;40:511-5.
Reckelhoff J. Gender differences in the regulation of blood pressure. Hypertension 2001;37:1199-208.
Levy BI, Ambrosio G, Pries AR, Struijker-Boudier HA. Microcirculation in hypertension: a new target for treatment? Circulation 2001;104:735-40.
Krause DN, Duckles SP, Pelligrino DA. Influence of sex steroid hormones on cerebrovascular function. J Appl Physiol 2006;101:1252-61.
Krejza J, Mariak Z, Huba M, Wolczynski S, Lewko J. Effect of endogenous estrogen on blood flow through carotid arteries. Stroke 2001;32:30-6.
Miller VM, Duckles SP. Vascular actions of estrogens: functional implications. Pharmacol Rev 2008;60:210-41.
Snyder HM, Corriveau RA, Craft S, Faber, JE, Greenberg, SM, and Knopman, D, et al. Vascular contributions to cognitive impairment and dementia including Alzheimer's disease. Alzheimers Dement 2015;11:710-17.
Losordo DW, Isner JM. Estrogen and angiogenesis. Arterioscler Thromb Vasc Biol 2001;21:6-12.
White RE. Estrogen and vascular function. Vascul Pharmacol 2002;38:73-80.
Lund CJ, Donovan JC. Blood volume during pregnancy. Am J Obstet Gynecol 1967;98:394-403.
Pritchard JA. Changes in the blood volume during pregnancy and delivery. Anesthesiology 1965;26:393-9.
Hytten FE, Paintin DB. Increase in plasma volume during normal pregnancy. J Obstet Gynaecol Br Emp 1963;70:402-7.
Rothe CF. Reflex control of veins and vascular capacitance. Physiol Rev 1983;63:1281-342.
Lee SP, Duong TQ, Yang G, Iadecola C, Kim SG. Relative changes of cerebral arterial and venous blood volumes during increased cerebral blood flow: implications for bold fMRI. Magn Reson Med 2001;45:791-800.
Niemczyk NA, Bertolet M, Catov JM, Desai, M, McClure, CK, and Roberts, JM, et al. Common carotid artery intima-media thickness increases throughout the pregnancy cycle: a prospective cohort study. BMC Pregnancy Childbirth 2018;18:195.
Manalo-Estrella P, Barker AE. Histopathologic findings in human aortic media associated with pregnancy. Arch Pathol 1967;83:336-41.
Cipolla MJ, Sweet JG, Chan SL. Cerebral vascular adaptation to pregnancy and its role in the neurological complications of eclampsia. J Appl Physiol 2011;110:329-39.
Morris EA, Hale SA, Badger GJ, Magness RR, Bernstein IM. Pregnancy induces persistent changes in vascular compliance in primiparous women. Am J Obstet Gynecol 2015;212:633.e1-e6.
Johnson AC, Cipolla MJ. The cerebral circulation during pregnancy: adapting to preserve normalcy. Physiology 2015;30:139-47.
Gao YR, Greene SE, Drew PJ. Mechanical restriction of intracortical vessel dilation by brain tissue sculpts the hemodynamic response. Neuroimage 2015;115:162-76.
Lisabeth LD, Reeves MJ, Baek J, Skolarus, LE, Brown, DL, and Zahuranec, DB, et al. Factors influencing sex differences in poststroke functional outcome. Stroke 2015;46:860-3.
Santalucia P, Pezzella FR, Sessa M, Monaco, S, Torgano, G, and Anticoli, S, et al. Sex differences in clinical presentation, severity and outcome of stroke: results from a hospital-based registry. Eur J Intern Med 2013;24:167-71.
Phan HT, Blizzard CL, Reeves MJ, Thrift, AG, Cadilhac, DA, and Sturm, J, et al. Factors contributing to sex differences in functional outcomes and participation after stroke. Neurology 2018;90:e1945-53.
Manwani B, McCullough LD. Sexual dimorphism in ischemic stroke: lessons from the laboratory. Women's Health 2011;7:319-39.
Hachinski V, Einhäupl K, Ganten D, Alladi, S, Brayne, C, and Stephan, BCM, et al. Preventing dementia by preventing stroke: the Berlin Manifesto. Alzheimers Dement 2019;15:961-84.
Iadecola C, Gottesman RF. Cerebrovascular alterations in Alzheimer disease incidental or pathogenic? Circ Res 2018;123:406-8.
Suter OC, Sunthorn T, Kraftsik R, Straubel, J, Darekar, P, and Khalili, K, et al. Cerebral hypoperfusion generates cortical watershed microinfarcts in Alzheimer disease. Stroke 2002;33:1986-92.
Devanand DP, Pradhaban G, Liu X, Khandji, A, De Santi, S, and Segal, S, et al. Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease. Neurology 2007;68:828-36.
Khan UA, Liu L, Provenzano FA, Berman, DE, Profaci, CP, and Sloan, R, et al. Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease. Nat Neurosci 2014;17:304-11.
Schmidt-Kastner R, Freund TF. Selective vulnerability of the hippocampus in brain ischemia. Neuroscience 1991;40:599-636.
Perosa V, Priester A, Ziegler G, Cardenas-Blanco, A, Dobisch, L, and Spallazzi, M, et al. Hippocampal vascular reserve associated with cognitive performance and hippocampal volume. Brain 2020;143:622-34.