Abstract
Impairment of cerebrovascular autoregulation (CAR) is common after brain injury, although the pathophysiology remains elusive. The mechanisms of vascular dysregulation, their impact on brain function, and potential therapeutic implications are still incompletely understood. Clinical assessment of CAR remains challenging. Observational studies suggest that CAR impairment is associated with worse outcomes, and that optimization of cerebral blood flow (CBF) by individual arterial blood pressure (ABP) targets could potentially improve outcome. We present a porcine closed cranial window model that measures the hemodynamic response of pial arterioles, the main site of CBF control, based on changes in their diameter and red blood cell velocity. This quantitative direct CAR assessment is compared to laser Doppler flow (LDF). CAR breakpoints are determined by segmented regression analysis and validated using LDF and brain tissue oxygen pressure. Using a standardized cortical impact, CAR impairment in traumatic brain injury can be studied using our method of combining pial arteriolar diameter and RBC velocity to quantify RBC flux in a large animal model. The model has numerous potential applications to investigate CAR physiology and pathophysiology of CAR impairment after brain injury, the impact of therapeutic interventions, drugs, and other confounders, or to develop personalized ABP management strategies.
Highlights
Cerebrovascular autoregulation (CAR) protects the brain against changes in cerebral perfusion pressure (CPP) by actively adjusting the vascular resistance to ensure a steady cerebral blood flow (CBF)
The role and implications of impaired cerebrovascular autoregulation (CAR) are increasingly being recognized in the pathophysiology of acute brain injuries such as traumatic brain injury (TBI), stroke, subarachnoid haemorrhage (SAH), or prematurity-related intracranial haemorrhage (ICH), and in chronic neurological conditions such as vascular dementia or Alzheimer’s disease[1,2]
A fraction of 4–7% of total circulating red blood cell (RBC) was fluorescently labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE), an intracellular fluorescent probe not influencing RBC rheology
Summary
Cerebrovascular autoregulation (CAR) protects the brain against changes in cerebral perfusion pressure (CPP) by actively adjusting the vascular resistance to ensure a steady cerebral blood flow (CBF). Pial arterioles on the cerebral cortex control the largest proportion of change in vascular resistance, and as such are the main site of CBF control. They play a key role in the protective autoregulation of CBF and in neurovascular coupling[2]. The use of a relevant animal model to study pial arteriolar regulation of CBF can allow translation of basic scientific advancements into clinical practice. Rodents models to study the vasodynamics of pial arteriolar flow have been developed, and use confocal or two-photon microscopy measurements of vessel diameters and RBC velocity. The larger size of the animal permits handling and catheterization that enable adequate physiological monitoring, with techniques and devices comparable to human patients in the intensive care unit
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