Integrative cerebral blood flow regulation in ischemic stroke

Abstract

Optimizing cerebral perfusion is key to rescuing salvageable ischemic brain tissue. Despite being an important determinant of cerebral perfusion, there are no effective guidelines for blood pressure (BP) management in acute stroke. The control of cerebral blood flow (CBF) involves a myriad of complex pathways which are largely unaccounted for in stroke management. Due to its unique anatomy and physiology, the cerebrovascular circulation is often treated as a stand-alone system rather than an integral component of the cardiovascular system. In order to optimize the strategies for BP management in acute ischemic stroke, a critical reappraisal of the mechanisms involved in CBF control is needed. In this review, we highlight the important role of collateral circulation and re-examine the pathophysiology of CBF control, namely the determinants of cerebral perfusion pressure gradient and resistance, in the context of stroke. Finally, we summarize the state of our knowledge regarding cardiovascular and cerebrovascular interaction and explore some potential avenues for future research in ischemic stroke.

Chronic cerebral hypoperfusion and blood-brain barrier disruption in uninjured brain areas of rhesus monkeys subjected to transient ischemic stroke

“…6 Post-reperfusion CBF can be mostly restored, but it remains unclear if it will ever return to its original level. [7][8][9] CBF is regulated at different levels, including 1) cerebral autoregulation, the cerebral vascular response to perfusion pressure; 2) NVC, a mechanism that results in local CBF regulation in response to localized active neurons; 3) vascular reactivity at arteriole or capillary level (including carbon dioxide). 5,[9][10][11] The blood-brain barrier (BBB) is an essential structure in the neurovascular unit (NVU) and plays a vital role in NVC.…”

How can integrative physiology advance stroke research and stroke care?

“…1 Fan and colleagues provide a comprehensive overview of these and many other examples showing how integrative physiology can be applied in the context of stroke. 2 In a closely related review, they subsequently illustrate how these concepts may be applied in clinical practice and clinical research. 9 For this Special Issue, we have selected four original research papers that illustrate the wide range of research applications of these concepts.…”

“…We cannot, and should not, answer these questions without integrative physiology. 1,2 Integrative physiology in stroke Just as an example, to begin to answer the question whether the brain may purposefully initiate hypertension in acute stroke, we have to understand the baroreflex function. 2 This system senses systemic blood pressure and uses feedback loops to adapt heart rate and peripheral vascular resistance to control it.…”

“…1,2 Integrative physiology in stroke Just as an example, to begin to answer the question whether the brain may purposefully initiate hypertension in acute stroke, we have to understand the baroreflex function. 2 This system senses systemic blood pressure and uses feedback loops to adapt heart rate and peripheral vascular resistance to control it. 3 There is no input from a 'brain blood flow sensor' into the baroreflex loop: even though its existence may seem logical, there is no known physiological mechanism by which the brain can sense a reduction in cerebral blood flow (CBF) and respond by increasing blood pressure.…”

“…However, recent work has indicated that astrocytes that lie adjacent to the brain stem centers involved in the autonomic nervous system, are responding to increased intracranial pressure, and can initiate transient hypertension through stimulation of these brain stem centers (for more context and discussion, see Claassen et al 4 ). This means that the acute hypertension in stroke could be a response to an increase in intracranial pressure, 1,2 although several other candidate mechanisms may be involved.…”