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Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury.

Østergaard L, Engedal TS, Aamand R, Mikkelsen R, Iversen NK, Anzabi M, Næss-Schmidt ET, Drasbek KR, Bay V, Blicher JU, Tietze A, Mikkelsen IK, Hansen B, Jespersen SN, Juul N, Sørensen JC, Rasmussen M - J. Cereb. Blood Flow Metab. (2014)

Bottom Line: In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed.We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI.We discuss diagnostic and therapeutic consequences of these predictions.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark [2] Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.

ABSTRACT
Most patients who die after traumatic brain injury (TBI) show evidence of ischemic brain damage. Nevertheless, it has proven difficult to demonstrate cerebral ischemia in TBI patients. After TBI, both global and localized changes in cerebral blood flow (CBF) are observed, depending on the extent of diffuse brain swelling and the size and location of contusions and hematoma. These changes vary considerably over time, with most TBI patients showing reduced CBF during the first 12 hours after injury, then hyperperfusion, and in some patients vasospasms before CBF eventually normalizes. This apparent neurovascular uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen diffusion into tissue, or microthrombosis. Capillary compression by astrocytic endfeet swelling is observed in biopsies acquired from TBI patients. In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed. We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI. The analysis suggests that elevated capillary transit time heterogeneity can cause critical reductions in oxygen availability in the absence of 'classic' ischemia. We discuss diagnostic and therapeutic consequences of these predictions.

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Capillary compression by astrocytic endfeet swelling after cerebral contusions. Astrocytic endfeet swelling and membrane disruption is a typical finding in humans 3 hours–3 days after cerebral contusions. (A) Shows a thin section through a cortical capillary. Note the massive swelling of the perivascular astrocytic foot process (a) and the flattening of the capillary lumen (L). Magnification × 400. (B) Shows a thin section through a white matter capillary, again with gross astrocytic foot process swelling (a) and compression of the capillary lumen (L). In this case, disruptions of the membranes that limit the foot process can be observed. Magnification × 3750. Reproduced from Bullock et al,26 with permission from the publisher.
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fig1: Capillary compression by astrocytic endfeet swelling after cerebral contusions. Astrocytic endfeet swelling and membrane disruption is a typical finding in humans 3 hours–3 days after cerebral contusions. (A) Shows a thin section through a cortical capillary. Note the massive swelling of the perivascular astrocytic foot process (a) and the flattening of the capillary lumen (L). Magnification × 400. (B) Shows a thin section through a white matter capillary, again with gross astrocytic foot process swelling (a) and compression of the capillary lumen (L). In this case, disruptions of the membranes that limit the foot process can be observed. Magnification × 3750. Reproduced from Bullock et al,26 with permission from the publisher.

Mentions: Glial swelling is a prominent feature of tissue specimens obtained early after cerebral contusions in humans. In tissue removed between 3 h and 3 days after injury, disruption and gross swelling of pericapillary astrocytic endfeet is a consistent finding, and this swelling is observed to cause compression of the capillary lumen26—see Figure 1. Astrocytic endfeet swelling is limited after day 3, but microvascular compression is typically still observed within the first week.26 Astrocytic endfeet swelling has been observed as early as 1 hour after TBI in rats,27 and results in baboons further suggest that this abnormality is an early and transient phenomenon that peaks 6 hours after injury.28 In biopsies obtained the first week after injury, the capillary lumen is also affected by capillary endothelial swelling, microvascular collapse, and perivascular edema.20


Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury.

Østergaard L, Engedal TS, Aamand R, Mikkelsen R, Iversen NK, Anzabi M, Næss-Schmidt ET, Drasbek KR, Bay V, Blicher JU, Tietze A, Mikkelsen IK, Hansen B, Jespersen SN, Juul N, Sørensen JC, Rasmussen M - J. Cereb. Blood Flow Metab. (2014)

Capillary compression by astrocytic endfeet swelling after cerebral contusions. Astrocytic endfeet swelling and membrane disruption is a typical finding in humans 3 hours–3 days after cerebral contusions. (A) Shows a thin section through a cortical capillary. Note the massive swelling of the perivascular astrocytic foot process (a) and the flattening of the capillary lumen (L). Magnification × 400. (B) Shows a thin section through a white matter capillary, again with gross astrocytic foot process swelling (a) and compression of the capillary lumen (L). In this case, disruptions of the membranes that limit the foot process can be observed. Magnification × 3750. Reproduced from Bullock et al,26 with permission from the publisher.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4269727&req=5

fig1: Capillary compression by astrocytic endfeet swelling after cerebral contusions. Astrocytic endfeet swelling and membrane disruption is a typical finding in humans 3 hours–3 days after cerebral contusions. (A) Shows a thin section through a cortical capillary. Note the massive swelling of the perivascular astrocytic foot process (a) and the flattening of the capillary lumen (L). Magnification × 400. (B) Shows a thin section through a white matter capillary, again with gross astrocytic foot process swelling (a) and compression of the capillary lumen (L). In this case, disruptions of the membranes that limit the foot process can be observed. Magnification × 3750. Reproduced from Bullock et al,26 with permission from the publisher.
Mentions: Glial swelling is a prominent feature of tissue specimens obtained early after cerebral contusions in humans. In tissue removed between 3 h and 3 days after injury, disruption and gross swelling of pericapillary astrocytic endfeet is a consistent finding, and this swelling is observed to cause compression of the capillary lumen26—see Figure 1. Astrocytic endfeet swelling is limited after day 3, but microvascular compression is typically still observed within the first week.26 Astrocytic endfeet swelling has been observed as early as 1 hour after TBI in rats,27 and results in baboons further suggest that this abnormality is an early and transient phenomenon that peaks 6 hours after injury.28 In biopsies obtained the first week after injury, the capillary lumen is also affected by capillary endothelial swelling, microvascular collapse, and perivascular edema.20

Bottom Line: In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed.We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI.We discuss diagnostic and therapeutic consequences of these predictions.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark [2] Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.

ABSTRACT
Most patients who die after traumatic brain injury (TBI) show evidence of ischemic brain damage. Nevertheless, it has proven difficult to demonstrate cerebral ischemia in TBI patients. After TBI, both global and localized changes in cerebral blood flow (CBF) are observed, depending on the extent of diffuse brain swelling and the size and location of contusions and hematoma. These changes vary considerably over time, with most TBI patients showing reduced CBF during the first 12 hours after injury, then hyperperfusion, and in some patients vasospasms before CBF eventually normalizes. This apparent neurovascular uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen diffusion into tissue, or microthrombosis. Capillary compression by astrocytic endfeet swelling is observed in biopsies acquired from TBI patients. In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed. We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI. The analysis suggests that elevated capillary transit time heterogeneity can cause critical reductions in oxygen availability in the absence of 'classic' ischemia. We discuss diagnostic and therapeutic consequences of these predictions.

Show MeSH
Related in: MedlinePlus