Cerebral Autoregulation and Neurovascular Coupling in Acute and Chronic Stroke.

Abstract

Stroke is currently the second leading cause of death worldwide, and results in significant morbidity, and poorer quality of life for those affected (1). Stroke can be classified under two major sub-types: ischaemic and haemorrhagic. Ischaemic stroke accounts for ~70% of all stroke, and results from arterial occlusion, usually through embolism or small vessel thrombosis (2). Haemorrhagic stroke is a result of arterial rupture in the brain (2). However, the two sub-types frequently co-exist, with similar risk factors (e.g., hypertension), and overlap in pathological mechanisms (3). Although stroke incidence has declined in high-income countries, it remains a prevalent issue amongst low and middle-income countries, disproportionately affecting a younger, working age population in these areas (1). The treatment of acute ischaemic stroke (AIS) has advanced over recent decades. Notably, the advent of both thrombolysis and mechanical thrombectomy has revolutionised the management of AIS, associated with reduced mortality, and improved functional outcome (2, 4, 5). Despite these advances, the management of haemorrhagic stroke has lagged behind, and treatment options are largely confined to reversal of anticoagulants and intensive blood pressure (BP) lowering (2). Conversely, in AIS, the target for BP management remains uncertain, and trials have largely shown equivalence (6, 7), or harm (8), associated with aggressive BP management strategies. To understand the mechanistic implications of BP lowering in AIS, studies have investigated the temporal changes in cerebral autoregulation (CA) following stroke (9). In healthy states, CA maintains a constant cerebral perfusion, despite fluctuations in systemic BP (10). However, the ability of the brain maintain CA may be compromised in the acute phase of stroke, increasing the vulnerability of the brain to hypoperfusion with intensive BP management strategies (11, 12). Conversely, surges in BP during this vulnerable phase may risk haemorrhagic transformation of the infarct, resulting in poorer outcomes (11, 12). Thus, understanding the temporal nature of CA in the acute phase of stroke could provide important mechanistic insights to guide BP management strategies in the clinical setting. A related concept to CA is the physiological mechanism of neurovascular coupling (NVC). Under healthy conditions, neuronal activity is tightly coupled to cerebral blood flow (CBF), such that increases in neuronal activity will result in increases in CBF to ensure the metabolic demands of the brain are met. Intact NVC is integral to maintain optimal cognitive function, and thus may be an important physiological mechanism in the chronic or rehabilitation phase of stroke. The following sections consider the evidence to support a role for CA and NVC as important mechanistic factors in the acute and chronic phases of stroke, and the key clinical and research implications going forward.