Quantification of capillary perfusion in an animal model of acute intracranial hypertension.

Intracranial hypertension (IH) is a common feature of many pathologies, including brain edema (BE). 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 (OCT) 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 minutes. WI induced severe IH and brain herniation. ICP and CPP reached 90.2 mmHg and 38.4 mmHg, respectively. FPV was significantly affected already at normal ICP (ICP < 15 mmHg, slope ≈ -1.46, p < 0.001) and, at the onset of IH (ICP = 20-22 mmHg), FPV was 17.9 ± 13.3 % lower than baseline. A decreasing trend was observed until the ICP peak (%FPV = -43.6 ± 19.2 %). In the ICP range of 7 - 42 mmHg, 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.