Нейроваскулярное взаимодействие и церебральная перфузия при старении, церебральной микроангиопатии и болезни Альцгеймера

L. A. Dobrynina1
1ФГБНУ «Научный центр неврологии», Москва, Россия

Аннотация


Сохранность нейроваскулярной единицы (НВЕ) и взаимодействия ее элементов является основой функционирования головного мозга. Исключительность НВЕ в обеспечении метаболизма всех церебральных процессов обосновывает облигатность участия в патофизиологии широкого круга неврологических заболеваний. Установленное сходство структурных изменений в НВЕ на ранних стадиях старения и гипертензивной церебральной микроангиопатии (ЦМА) позволяет предполагать единство патогенетических механизмов ее повреждения при разных типах патологических процессов и, с учетом обратимости ранних изменений нейроваскулярного взаимодействия (НВВ), дает возможность рассматривать некоторые формы ЦМА в качестве вариантов раннего ускоренного старения сосудистой стенки. Понимание повреждения мелких сосудов в качестве значимого фактора риска болезни Альцгеймера и смешанных форм деменций положило начало пересмотру представлений о развитии когнитивных расстройств. Показана универсальная роль ранних нарушений НВВ в развитии разных видов деменций. Последующие исследования должны улучшить понимание механизмов нарушений НВВ, роль классических и вновь уточняемых факторов риска в их развитии и возможности превентивных стратегий. Очевидно, что успехи могут быть достигнуты при совместной работе исследователей в области нейронаук, позволяющей адаптировать достижения в области фундаментальных исследований в прикладные разработки, востребованные в клинической практике.

Литература

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Ключевые слова

нейроваскулярная единица; нейроваскулярное взаимодействие; старение; церебральная микроангиопатия; артериальная гипертензия; болезнь Альцгеймера; церебральная перфузия

Полный текст:

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Литература

Zlokovic B. V. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 2011; 12 (12): 723. DOI:org/10.1038/nrn3114. PMID: 22048062.

World Health Organization. Dementia: a public health priority. 2012. www.who.int/mental_health/publications/dementia_report_2012/en/

Zhao Z.; Nelson A.R.; Betsholtz C.; Zlokovic B.V. Establishment and dysfunction of the blood-brain barrier. Cell 2015; 163 (5): 1064–1078. DOI: 10.1016/j.cell.2015.10.067. PMID: 26590417.

Kisler K.; Nelson A.R.; Montagne A.; Zlokovic B.V. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci 2017; 18 (7): 419. DOI: 10.1038/nrn.2017.48. PMID: 28515434.

Fernández-Klett F.; Offenhauser N.; Dirnagl U. et al. Pericytes in capillaries are contractile in vivo; but arterioles mediate functional hyperemia in the mouse brain. Proc Natl Acad Sci USA 2010; 107 (51): 22290–22295. DOI: org/10.1073/pnas.1011321108. PMID: 21135230.

Dunn K.M.; Nelson M.T. Neurovascular signaling in the brain and the pathological consequences of hypertension. Am J Physiol Heart Circ Physiol 2013; 306 (1): H1–H14. DOI: 10.1152/ajpheart.00364.2013. PMID: 24163077.

Sakadžić S.; Mandeville E.T.; Gagnon L. et al. Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue. Nat Commun 2014; 5: 5734. DOI: 10.1038/ncomms6734. PMID: 25483924.

Amin-Hanjani S.; Du X.; Pandey D.K. et al. Effect of age and vascular anatomy on blood flow in major cerebral vessels. J Cerebral Blood Flow Metab 2015;35 (2): 312–318. DOI: dx.DOI.org/10.1038/jcbfm.2014.203. PMID: 25388677.

Zonta M.; Angulo M.C.; Gobbo S. et al. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 2003; 6 (1):43. DOI: dx.DOI.org/10.1038/nn980. PMID: 12469126.

Hyder F.; Patel A.B.; Gjedde A. et al. Neuronal–glial glucose oxidation and glutamatergic–GABAergic function. J Cerebral Blood Flow Metab 2006; 26 (7):865–877. DOI: org/10.1038%2Fsj.jcbfm.9600263. PMID: 16407855.

Straub S.V.; Nelson M.T. Astrocytic calcium signaling: the information currency coupling neuronal activity to the cerebral microcirculation. Trends Cardiovasc Med 2007; 17 (6): 183–190. DOI: org/10.1016/j.tcm.2007.05.001. PMID: 17662912.

Gordon G.R.; Mulligan S.J.; MacVicar B.A. Astrocyte control of the cerebrovasculature. Glia 2007; 55 (12): 1214–1221. DOI: org/10.1002/glia.20543. PMID: 17659528.

Rosenegger D.G.; Tran C.H.T.; Cusulin J.I.W.; Gordon G.R. Tonic local brain blood flow control by astrocytes independent of phasic neurovascular coupling. J Neurosci 2015; 35 (39): 13463–13474. DOI: dx.DOI.org/10.1523/JNEUROSCI.1780-15.2015. PMID: 26424891

Filosa J.A.; Bonev A.D.; Straub S.V. et al. Local potassium signaling couples neuronal activity to vasodilation in the brain. Nat Neurosci 2006; 9 (11): 1397. DOI: org/10.1038/nn1779. PMID: 17013381.

Toth P.; Tarantini S.; Davila A. et al. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex. Am J Physiol Heart Circ Physiol 2015;309 (11): H1837–H1845. DOI: dx.DOI.org/10.1152/ajpheart.00463.2015.PMID: 26453330.

Neuwelt E. A.; Bauer B.; Fahlke C. et al. Engaging neuroscience to advance translational research in brain barrier biology. Nat Rev Neurosci 2011; 12 (3): 169. DOI: org/10.1038/nrn2995. PMID: 21331083.

Kliche K.; Jeggle P.; Pavenstädt H.; Oberleithner H. Role of cellular mechanics in the function and life span of vascular endothelium. Pflügers Arch 2011; 462 (2): 209–217. DOI: 10.1007/s00424-011-0929-2. PMID: 21318292.

Wang M.; Jiang L.; Monticone R.E.; Lakatta E.G. Proinflammation: the key to arterial aging. Trends Endocrin Metab 2014; 25 (2): 72–79. DOI: 10.1016/j. tem.2013.10.002. PMID: 24365513.

Csiszar A.; Labinskyy N.; Zhao X. et al. Vascular superoxide and hydrogen peroxide production and oxidative stress resistance in two closely related rodent species with disparate longevity. Aging Cell 2007; 6 (6): 783–797. DOI:org/10.1111/j.1474-9726.2007.00339.x. PMID: 17925005.

Kao C.L.; Chen L.K.; Chang Y.L. et al. Resveratrol protects human endothelium from H2O2-induced oxidative stress and senescence via SirT1 activation. J Atheroscler Thromb 2010; 17 (9): 970–979. PMID: 20644332.

Asai K.; Kudej R. K.; Shen Y.T. et al. Peripheral vascular endothelial dysfunction and apoptosis in old monkeys. Arterioscler Thromb Vasc Biol 2000; 20 (6):1493–1499. DOI: 10.1161/01.ATV.20.6.1493. PMID: 10845863.

Tanaka Y.; Moritoh Y.; Miwa N. Age – dependent telomere – shortening is repressed by phosphorylated α-tocopherol together with cellular longevity and intracellular oxidative – stress reduction in human brain microvascular endotheliocytes. J Cell Biochem 2007; 102 (3): 689–703. DOI: org/10.1002/jcb.21322.PMID: 17407150.

Wang M.; Zhang J.; Walker S. J. et al. Involvement of NADPH oxidase in age-associated cardiac remodeling. J Mol Cell Cardiol 2010; 48 (4): 765–772. DOI: 10.1016/j.yjmcc.2010.01.006. PMID: 20079746.

Chen J.; Huang X.; Halicka D. et al. Contribution of p16 INK4a and p21 CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53. Am J Physiol Heart Circ Physiol 2006; 290 (4): H1575–H1586. DOI:org/10.1152/ajpheart.00364.2005. PMID: 16243918.

Wang M.; Zhang J.; Jiang L. Q. et al. Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension 2007; 50 (1): 219–227. DOI: 10.1161/HYPERTENSIONAHA.107.089409. PMID: 17452499

Mistry Y.; Poolman T.; Williams B.; Herbert K. E. A role for mitochondrial oxidants in stress-induced premature senescence of human vascular smooth muscle cells. Redox Biol 2013; 1 (1): 411–417. DOI: org/10.1016/j.redox.2013.08.004.PMID: 24191234.

Ragnauth C.D.; Warren D.T.; Liu Y. et al. Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation 2010; 121 (20): 2200–2210. DOI: 10.1161/CIRCULATIONAHA.109.902056. PMID: 20458013.

Csiszar A.; Sosnowska D.; Wang M. et al. Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment. J Gerontol A Biomed Sci Med Sci 2012; 67 (8): 811–820. DOI: org/10.1093/gerona/glr228. PMID: 22219513.

Wang M.; Lakatta E. G. The salted artery and angiotensin II signaling: a deadly duo in arterial disease. J Hypertension 2009; 27 (1): 19. DOI: org/10.1097%2FHJH.0b013e32831d1fed. PMID: 19050444.

Wang M.; Zhang; J.; Telljohann R. et al. Chronic matrix metalloproteinase inhibition retards age-associated arterial proinflammation and increase in blood pressure. Hypertension 2012; 60 (2): 459–466. DOI: org/10.1161%2FHYPERTENSIONAHA.112.191270. PMID: 22689745.

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DOI: http://dx.doi.org/10.25692/ACEN.2018.5.11