The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage.
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.
1] Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark [2] Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
Leif
L
Østergaard
Rasmus
R
Aamand
Sanja
S
Karabegovic
Anna
A
Tietze
Jakob Udby
JU
Blicher
Irene Klaerke
IK
Mikkelsen
Nina Kerting
NK
Iversen
Niels
N
Secher
Thorbjørn Søndergaard
TS
Engedal
Mariam
M
Anzabi
Eugenio Gutierrez
EG
Jimenez
Changsi
C
Cai
Klaus Ulrik
KU
Koch
Erhard Trillingsgaard
ET
Naess-Schmidt
Annette
A
Obel
Niels
N
Juul
Mads
M
Rasmussen
Jens Christian Hedemann
JC
Sørensen
D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008833:Microcirculation; D055806:Microvessels / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology