The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage

Leif Østergaard; Rasmus Aamand; Sanja Karabegovic; Anna Tietze; Jakob Udby Blicher; Irene Klærke Mikkelsen; Nina Kerting Iversen; Niels Secher; Thorbjørn Søndergaard Engedal; Maryam Anzabi; Eugenio Gutierrez Jimenez; Changsi Cai; Klaus Ulrik Koch; Erhard Trillingsgaard Næss-Schmidt; Annette Obel; Niels Juul; Mads Rasmussen; Jens Christian Hedemann Sørensen

doi:10.1038/jcbfm.2013.173

The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage

Leif Østergaard, Rasmus Aamand, Sanja Karabegovic, Anna Tietze, Jakob Udby Blicher, Irene Klærke Mikkelsen, Nina Kerting Iversen, Niels Secher, Thorbjørn Søndergaard Engedal, Maryam Anzabi, Eugenio Gutierrez Jimenez, Changsi Cai, Klaus Ulrik Koch, Erhard Trillingsgaard Næss-Schmidt, Annette Obel, Niels Juul, Mads Rasmussen, Jens Christian Hedemann Sørensen

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Abstract

The mortality after aneurysmal subarachnoid hemorrhage (SAH) is 50%, and most survivors suffer severe functional and cognitive deficits. Half of SAH patients deteriorate 5 to 14 days after the initial bleeding, so-called delayed cerebral ischemia (DCI). Although often attributed to vasospasms, DCI may develop in the absence of angiographic vasospasms, and therapeutic reversal of angiographic vasospasms fails to improve patient outcome. The etiology of chronic neurodegenerative changes after SAH remains poorly understood. Brain oxygenation depends on both cerebral blood flow (CBF) and its microscopic distribution, the so-called capillary transit time heterogeneity (CTH). In theory, increased CTH can therefore lead to tissue hypoxia in the absence of severe CBF reductions, whereas reductions in CBF, paradoxically, improve brain oxygenation if CTH is critically elevated. We review potential sources of elevated CTH after SAH. Pericyte constrictions in relation to the initial ischemic episode and subsequent oxidative stress, nitric oxide depletion during the pericapillary clearance of oxyhemoglobin, vasogenic edema, leukocytosis, and astrocytic endfeet swelling are identified as potential sources of elevated CTH, and hence of metabolic derangement, after SAH. Irreversible changes in capillary morphology and function are predicted to contribute to long-term relative tissue hypoxia, inflammation, and neurodegeneration. We discuss diagnostic and therapeutic implications of these predictions.Journal of Cerebral Blood Flow & Metabolism advance online publication, 25 September 2013; doi:10.1038/jcbfm.2013.173.

Original language	English
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	33
Issue	12
Pages (from-to)	1825-37
Number of pages	17
ISSN	0271-678X
DOIs	https://doi.org/10.1038/jcbfm.2013.173
Publication status	Published - 25 Sept 2013

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Østergaard, L., Aamand, R., Karabegovic, S., Tietze, A., Blicher, J. U., Mikkelsen, I. K., Iversen, N. K., Secher, N., Engedal, T. S., Anzabi, M., Jimenez, E. G., Cai, C., Koch, K. U., Næss-Schmidt, E. T., Obel, A., Juul, N., Rasmussen, M., & Sørensen, J. C. H. (2013). The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism, 33(12), 1825-37. https://doi.org/10.1038/jcbfm.2013.173

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title = "The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage",

abstract = "The mortality after aneurysmal subarachnoid hemorrhage (SAH) is 50%, and most survivors suffer severe functional and cognitive deficits. Half of SAH patients deteriorate 5 to 14 days after the initial bleeding, so-called delayed cerebral ischemia (DCI). Although often attributed to vasospasms, DCI may develop in the absence of angiographic vasospasms, and therapeutic reversal of angiographic vasospasms fails to improve patient outcome. The etiology of chronic neurodegenerative changes after SAH remains poorly understood. Brain oxygenation depends on both cerebral blood flow (CBF) and its microscopic distribution, the so-called capillary transit time heterogeneity (CTH). In theory, increased CTH can therefore lead to tissue hypoxia in the absence of severe CBF reductions, whereas reductions in CBF, paradoxically, improve brain oxygenation if CTH is critically elevated. We review potential sources of elevated CTH after SAH. Pericyte constrictions in relation to the initial ischemic episode and subsequent oxidative stress, nitric oxide depletion during the pericapillary clearance of oxyhemoglobin, vasogenic edema, leukocytosis, and astrocytic endfeet swelling are identified as potential sources of elevated CTH, and hence of metabolic derangement, after SAH. Irreversible changes in capillary morphology and function are predicted to contribute to long-term relative tissue hypoxia, inflammation, and neurodegeneration. We discuss diagnostic and therapeutic implications of these predictions.Journal of Cerebral Blood Flow & Metabolism advance online publication, 25 September 2013; doi:10.1038/jcbfm.2013.173.",

author = "Leif {\O}stergaard and Rasmus Aamand and Sanja Karabegovic and Anna Tietze and Blicher, {Jakob Udby} and Mikkelsen, {Irene Kl{\ae}rke} and Iversen, {Nina Kerting} and Niels Secher and Engedal, {Thorbj{\o}rn S{\o}ndergaard} and Maryam Anzabi and Jimenez, {Eugenio Gutierrez} and Changsi Cai and Koch, {Klaus Ulrik} and N{\ae}ss-Schmidt, {Erhard Trillingsgaard} and Annette Obel and Niels Juul and Mads Rasmussen and S{\o}rensen, {Jens Christian Hedemann}",

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Østergaard, L , Aamand, R, Karabegovic, S, Tietze, A, Blicher, JU, Mikkelsen, IK, Iversen, NK, Secher, N , Engedal, TS, Anzabi, M, Jimenez, EG, Cai, C, Koch, KU, Næss-Schmidt, ET, Obel, A, Juul, N , Rasmussen, M & Sørensen, JCH 2013, 'The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage', Journal of Cerebral Blood Flow and Metabolism, vol. 33, no. 12, pp. 1825-37. https://doi.org/10.1038/jcbfm.2013.173

The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage. / Østergaard, Leif ; Aamand, Rasmus; Karabegovic, Sanja et al.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 33, No. 12, 25.09.2013, p. 1825-37.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage

AU - Østergaard, Leif

AU - Aamand, Rasmus

AU - Karabegovic, Sanja

AU - Tietze, Anna

AU - Blicher, Jakob Udby

AU - Mikkelsen, Irene Klærke

AU - Iversen, Nina Kerting

AU - Secher, Niels

AU - Engedal, Thorbjørn Søndergaard

AU - Anzabi, Maryam

AU - Jimenez, Eugenio Gutierrez

AU - Cai, Changsi

AU - Koch, Klaus Ulrik

AU - Næss-Schmidt, Erhard Trillingsgaard

AU - Obel, Annette

AU - Juul, Niels

AU - Rasmussen, Mads

AU - Sørensen, Jens Christian Hedemann

PY - 2013/9/25

Y1 - 2013/9/25

N2 - The mortality after aneurysmal subarachnoid hemorrhage (SAH) is 50%, and most survivors suffer severe functional and cognitive deficits. Half of SAH patients deteriorate 5 to 14 days after the initial bleeding, so-called delayed cerebral ischemia (DCI). Although often attributed to vasospasms, DCI may develop in the absence of angiographic vasospasms, and therapeutic reversal of angiographic vasospasms fails to improve patient outcome. The etiology of chronic neurodegenerative changes after SAH remains poorly understood. Brain oxygenation depends on both cerebral blood flow (CBF) and its microscopic distribution, the so-called capillary transit time heterogeneity (CTH). In theory, increased CTH can therefore lead to tissue hypoxia in the absence of severe CBF reductions, whereas reductions in CBF, paradoxically, improve brain oxygenation if CTH is critically elevated. We review potential sources of elevated CTH after SAH. Pericyte constrictions in relation to the initial ischemic episode and subsequent oxidative stress, nitric oxide depletion during the pericapillary clearance of oxyhemoglobin, vasogenic edema, leukocytosis, and astrocytic endfeet swelling are identified as potential sources of elevated CTH, and hence of metabolic derangement, after SAH. Irreversible changes in capillary morphology and function are predicted to contribute to long-term relative tissue hypoxia, inflammation, and neurodegeneration. We discuss diagnostic and therapeutic implications of these predictions.Journal of Cerebral Blood Flow & Metabolism advance online publication, 25 September 2013; doi:10.1038/jcbfm.2013.173.

AB - The mortality after aneurysmal subarachnoid hemorrhage (SAH) is 50%, and most survivors suffer severe functional and cognitive deficits. Half of SAH patients deteriorate 5 to 14 days after the initial bleeding, so-called delayed cerebral ischemia (DCI). Although often attributed to vasospasms, DCI may develop in the absence of angiographic vasospasms, and therapeutic reversal of angiographic vasospasms fails to improve patient outcome. The etiology of chronic neurodegenerative changes after SAH remains poorly understood. Brain oxygenation depends on both cerebral blood flow (CBF) and its microscopic distribution, the so-called capillary transit time heterogeneity (CTH). In theory, increased CTH can therefore lead to tissue hypoxia in the absence of severe CBF reductions, whereas reductions in CBF, paradoxically, improve brain oxygenation if CTH is critically elevated. We review potential sources of elevated CTH after SAH. Pericyte constrictions in relation to the initial ischemic episode and subsequent oxidative stress, nitric oxide depletion during the pericapillary clearance of oxyhemoglobin, vasogenic edema, leukocytosis, and astrocytic endfeet swelling are identified as potential sources of elevated CTH, and hence of metabolic derangement, after SAH. Irreversible changes in capillary morphology and function are predicted to contribute to long-term relative tissue hypoxia, inflammation, and neurodegeneration. We discuss diagnostic and therapeutic implications of these predictions.Journal of Cerebral Blood Flow & Metabolism advance online publication, 25 September 2013; doi:10.1038/jcbfm.2013.173.

U2 - 10.1038/jcbfm.2013.173

DO - 10.1038/jcbfm.2013.173

M3 - Journal article

C2 - 24064495

SN - 0271-678X

VL - 33

SP - 1825

EP - 1837

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 12

ER -

The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage

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