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.

Keywords: Ischemic stroke; cerebral blood flow; neurovascular physiology.

Figure 1.

Relationship between blood pressure and stroke morality rate at 1 and 12 months. Systolic blood pressure (panel a) and diastolic blood pressure (panel b) on admission. Triangles and squares represent early and late stroke mortality rate, respectively, within groups A and B; Data are presented as mean ± 95% confidence intervals. Reprinted with permission.

Figure 2.

Pathophysiology changes in cerebral perfusion, metabolism and oxygen extraction in cerebral ischemia. The initial decline in regional cerebral blood flow (CBF) is compensated by a mirror rise in regional oxygen extraction fraction (OEF). Since the increase in OEF is unable to sustain the energy requirement of the brain, regional cerebral oxygen metabolism (CMRO₂) falls to the level of cerebral oxygen delivery. Over time, CMRO₂ falls further despite no further decrease in CBF, resulting in a decrease in OEF. Restoring CBF with reperfusion therapy or recruitment of collateral pathways will increase CBF (i.e., ‘luxury perfusion’) and concurrent decrease in OEF below baseline while CMRO₂ remain unchanged. Reprinted with permission.

Figure 3.

Relationship between mean arterial pressure and cerebral blood flow. All individual lines represent individual studies; the length of each line indicates the range of mean arterial pressure (MAP) change of the study. Average slope (thicker line) was 0.83% MAP/% CBF for decreasing MAP (n = 23), and 0.21% MAP/% CBF for increasing MAP (n = 26). Modified from Numan et al.

Figure 4.

Schematic representation of the inter-relationship between raised intracranial pressure and decreased cerebral perfusion to sympathetic outflow and arterial pressure, via known signaling pathways in the rostral ventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS). Modified from McBryde et al.

Figure 5.

Schematic representation of the effect of ischemic stroke on integrative cerebrovascular physiology. Cerebral perfusion pressure is the net balance of post-stroke hypertension, mediated by increased sympathetic activity, and changes in intracranial and cerebral venous pressure. Increases in intracranial pressure acts to decrease cerebral perfusion pressure and increase cerebral venous pressure. The latter serves to impede outflow of blood from the brain, thereby limit cerebral perfusion. Both baroreflex sensitivity and cerebral autoregulation appears to be impaired following stroke. This increases blood pressure variability and accentuates hyper- and hypoperfusion insults to the brain. Decreases in both cerebral perfusion and metabolic rate for oxygen following stroke are partially compensated by increased oxygen extraction fraction in the brain.