Quantification of Capillary Perfusion in an Animal Model of Acute Intracranial Hypertension

Abstract

Intracranial hypertension (IH) is a common feature of many pathologies, including brain edema. In the brain, the extended network of capillaries ensures blood flow to meet local metabolic demands. Capillary circulation may be severely affected by IH, but no studies have quantified the effect of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) on capillary perfusion during the development of brain edema. We used optical coherence tomography angiography to quantify relative changes of fractional perfused volume (FPV) in cortical capillaries and simultaneously monitored ICP and blood pressure (BP) in anesthetized male C57Bl/6NTac mice during development of brain edema induced by water intoxication (WI) within 30 min. WI induced severe IH and brain herniation. ICP and CPP reached 90.2 mm Hg and 38.4 mm Hg, respectively. FPV was significantly affected already at normal ICP (ICP <15 mm Hg, slope & -1.46, p < 0.001) and, at the onset of IH (ICP = 20-22 mm Hg), FPV was 17.9 -13.3% lower than baseline. A decreasing trend was observed until the ICP peak (D%FPV = -43.6 -19.2%). In the ICP range of 7-42 mm Hg, relative changes in FPV were significantly correlated with ICP, BP, and CPP ( p < 0.001), with ICP and CPP being the best predictors. In conclusion, elevated ICP induces a gradual collapse of the cerebral microvasculature, which is initiated before the clinical threshold of IH. In summary, the estimate of capillary perfusion might be essential in patients with IH to assess the state of the brain microcirculation and to improve the availability of oxygen and nutrients to the brain.

Deletion of aquaporin‐4 improves capillary blood flow distribution in brain edema

“…Moreover, the removal of AQP4 water channels played a beneficial role for microvascular blood flow, in addition to its general effects on edema formation, affecting how the In the late stage of pathological conditions associated with severe flow-restriction, as within the ischemic penumbra in stroke, low RTH values may indicate widespread collapse of the capillary network (Engedal et al, 2018). Also during brain edema, elevated ICP even within a moderate range (15-22 mmHg) could reduce the number of perfused brain microvessels (Bordoni et al, 2021;Bragin et al, 2011).…”

“…Using 2PLSM of mice subjected to water intoxication causing mild cytotoxic brain edema (Bordoni et al, 2021) with preserved blood brain barrier integrity (Adler et al, 1993;Melton et al, 1987), we show in non-anesthetized mice that capillary flow dynamics are profoundly affected during brain edema formation, and that removal of AQP4 significantly improves flow dynamics at any level of ICP increase. Moreover, we find reduced astrocytic Ca 2+ signaling in perivascular astrocytic endfeet in mice devoid of AQP4, suggesting a role for endfoot Ca 2+ in regulating microvascular flow dynamics in edema.…”

Fine tuning of neurointensive care in aneurysmal subarachnoid hemorrhage: From one-size-fits-all towards individualized care

“… 17 High ICP may in turn induce compression of neural structures as well as lead to macro- and microvascular CBF disturbances by lowering CPP and inducing capillary collapse. 18 …”

Mathematical modelling of haemorrhagic transformation within a multiscale microvasculature network

“…Wang and Payne (2021) discussed the effects of capillary compression based on experimental data (Bordoni et al 2020). However, this approach is less suitable for determining the capillary compression for large arterioles ( m > D 25 m).…”

“…Properties such as cerebral blood volume (CBV ) and perfusion rate are estimated and compared with clinical imaging data. Due to the increase in intracranial pressure (ICP) after HT, we also consider the effects of capillary compression in the vasculature, both in the damaged vessel and in other healthy vessels (Bordoni et al 2020). In addition, tissue displacement caused by the breakdown of BBB is calculated, using the methods proposed by Mokhtarudin and Payne (2015).…”