Abstract
In order to maintain proper function, mammalian brain requires a significant fraction of the energy provided through whole body oxygen consumption and oxidative phosphorylation. This has been fairly well known for a long time. More recently there has been an increased appreciation that, while whole brain blood flow remains fairly constant, there are large regional changes in local blood flow to account for spatial and temporal heterogeneity of neuronal activity. This latter phenomenon requires an extensive regulatory system for local oxygen delivery that involves arteriolar and capillary control mechanisms. The ISOTT has been a major contributor to the study of oxygen supply and demand through studies of the mechanisms of vascular dilation and constriction in response to energy expenditure and availability of substrate and oxygen. Nevertheless, it has become clear in the past few decades that in addition to acute, physiological responses to energy demand and oxygen/substrate availability, there are regulatory mechanisms that are continuously operating to control the capillary distribution over a time course of weeks. This process of “angioplasticity” results in the gradual acclimatization of the brain capillary bed to prolonged changes in oxygen/substrate availability and/or neuronal activity patterns. Angioplasticity is primarily regulated through the hypoxia inducible transcription factor, acting as a detector of the balance between oxygen delivery and energy demand at the level of the cell redox state, controlling vascular endothelial growth factor production which helps determine capillary density in consort with the cyclooxygenase-2/angiopoietin-2 pathway that controls endothelial cell junction mechanical stability. We can conclude that the structure-function of brain capillaries is regulated during prolonged challenges to energy supply-demand balance within the physiological range. We can conclude that over the physiological range of ambient oxygen, brain capillary density is proportional to fraction inspired oxygen. The primary mechanisms for regulation of brain capillary density are HIF-1/VEGF and COX-2/PGE2/ang-2 pathways of angiogenesis and angiolysis.
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Ndubuizu O, LaManna JC (2007) Brain tissue oxygen concentration measurements. Antioxid Redox Signal 9:1207–1219
Ugurbil K, Hu X, Chen W et al (1999) Functional mapping in the human brain using high magnetic fields. Philos Trans R Soc Lond B Biol Sci 354:1195–1213
Hyder F, Rothman DL (2012) Quantitative fMRI and oxidative neuroenergetics. Neuroimage 62:985–994
LaManna JC (1992) Rat brain adaptation to chronic hypobaric hypoxia. Adv Exp Med Biol 317:107–114
Zhang Y, Kuang Y, LaManna JC et al (2013) Contribution of brain glucose and ketone bodies to oxidative metabolism. Adv Exp Med Biol 765:365–370
Zhang Y, Kuang Y, Xu K et al (2013) Ketosis proportionately spares glucose utilization in brain. J Cereb Blood Flow Metab 33:1307–1311
LaManna JC (2012) Angioplasticity and cerebrovascular remodeling. Adv Exp Med Biol 737:13–17
LaManna JC, Vendel LM, Farrell RM (1992) Brain adaptation to chronic hypobaric hypoxia in rats. J Appl Physiol 72:2238–2243
Harik N, Harik S, Kuo N et al (1996) Time-course and reversibility of the hypoxia-induced alterations in cerebral vascularity and cerebral capillary glucose transporter density. Brain Res 737:335–338
Pichiule P, LaManna JC (2002) Angiopoietin-2 and rat brain capillary remodeling during adaptation and de-adaptation to prolonged mild hypoxia. J Appl Physiol 93:1131–1139
Benderro GF, LaManna JC (2014) HIF-1alpha/COX-2 expression and mouse brain capillary remodeling during prolonged moderate hypoxia and subsequent re-oxygenation. Brain Res 1569:41–47
Benderro GF, Sun X, Kuang Y et al (2012) Decreased VEGF expression and microvascular density, but increased HIF-1 and 2alpha accumulation and EPO expression in chronic moderate hyperoxia in the mouse brain. Brain Res 1471:46–55
Benderro GF, Tsipis CP, Sun X et al (2013) Increased HIF-1alpha and HIF-2alpha accumulation, but decreased microvascular density, in chronic hyperoxia and hypercapnia in the mouse cerebral cortex. Adv Exp Med Biol 789:29–35
Puchowicz MA, Xu K, Sun X et al (2007) Diet-induced ketosis increases capillary density without altered blood flow in rat brain. Am J Physiol Endocrinol Metab 292:E1607–E1615
Black JE, Zelazny AM, Greenough WT (1991) Capillary and mitochondrial support of neural plasticity in adult rat visual cortex. Exp Neurol 111:204–209
Black JE, Isaacs KR, Anderson BJ et al (1990) Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc Nat Acad Sci USA 87:5568–5572
Isaacs KR, Anderson BJ, Alcantara AA et al (1992) Exercise and the brain: Angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning. J Cereb Blood Flow Metab 12:110–119
Swain RA, Harris AB, Wiener EC et al (2003) Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat. Neuroscience 117:1037–1046
Black JE, Sirevaag AM, Greenough WT (1987) Complex experience promotes capillary formation in young rat visual cortex. Neurosci Lett 83:351–355
Sirevaag AM, Black JE, Shafron D et al (1988) Direct evidence that complex experience increases capillary branching and surface area in visual cortex of young rats. Brain Res 471:299–304
He C, Tsipis CP, LaManna JC et al (2017) Environmental Enrichment Induces Increased Cerebral Capillary Density and Improved Cognitive Function in Mice. Adv Exp Med Biol 977:175–181
Chavez J, Agani F, Pichiule P et al (2000) Expression of hypoxia-inducible factor-1 alpha in the brain of rats during chronic hypoxia. J Appl Physiol 89:1937–1942
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LaManna, J.C. (2018). Cerebral Angioplasticity: The Anatomical Contribution to Ensuring Appropriate Oxygen Transport to Brain. In: Thews, O., LaManna, J., Harrison, D. (eds) Oxygen Transport to Tissue XL. Advances in Experimental Medicine and Biology, vol 1072. Springer, Cham. https://doi.org/10.1007/978-3-319-91287-5_1
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DOI: https://doi.org/10.1007/978-3-319-91287-5_1
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