Intracranial mechanisms for preserving brain blood flow in health and disease

Abstract

The brain is an exceptionally energetically demanding organ with little metabolic reserve, and multiple systems operate to protect and preserve the brain blood supply. But how does the brain sense its own perfusion? In this review, we discuss how the brain may harness the cardiovascular system to counter threats to cerebral perfusion sensed via intracranial pressure (ICP), cerebral oxygenation and ischaemia. Since the work of Cushing over 100 years ago, the existence of brain baroreceptors capable of eliciting increases in sympathetic outflow and blood pressure has been hypothesized. In the clinic, this response has generally been thought to occur only in extremis, to perfuse the severely ischaemic brain as cerebral autoregulation fails. We review evidence that pressor responses may also occur with smaller, physiologically relevant increases in ICP. The incoming brain oxygen supply is closely monitored by the carotid chemoreceptors; however, hypoxia and other markers of ischaemia are also sensed intrinsically by astrocytes or other support cells within brain tissue itself and elicit reactive hyperaemia. Recent studies suggest that astrocytic oxygen signalling within the brainstem may directly affect sympathetic nerve activity and blood pressure. We speculate that local cerebral oxygen tension is a major determinant of the mean level of arterial pressure and discuss recent evidence that this may be the case. We conclude that intrinsic intra- and extra-cranial mechanisms sense and integrate information about hypoxia/ischaemia and ICP and play a major role in determining the long-term level of sympathetic outflow and arterial pressure, to optimize cerebral perfusion.

Intracranial pressure influences the level of sympathetic tone

“…The primary function of the cardiovascular system is to maintain organ perfusion. An emerging hypothesis in the development of cardiovascular disease is that the metabolically demanding brain puts the utmost priority on protecting its own blood supply, even if this comes at the "cost" of high blood pressure (BP) to the rest of the body, termed the selfish brain hypothesis (5,15,18). This is supported by recent data in human subjects, where congenital cerebrovascular abnormalities associated with cerebral hypoperfusion are strongly predictive of hypertension (26).…”

Involvement of endogenous central hydrogen sulfide (H2S) in hypoxia-induced hypothermia in spontaneously hypertensive rats

“…SHR exhibit physiopathological features including sympathetic hyperactivity which may account for their abnormal adjustments of Tb (Campos et al 2014;Collins et al 1987;Hajós and Engberg 1986;Morley et al 1990;O'Donnell and Volicer 1981;Okamoto and Aoki 1963;Trippodo and Frohlich 1981). Therefore, the present data shed light on the putative impacts of sympathetic hyperactivity on the adjustments of Tb under conditions of limited oxygen supply which may occur as a consequence of trauma, heart failure, ischemic stroke, etc (for a review see McBryde et al 2016).…”

Factors Associated With Choroidal Blood Flow Regulation in Healthy Young Subjects

“…The latter result is in agreement with previous reports in the brain. 67,68 Fasting glucose, cholesterol, triglycerides, creatinine, Creactive protein plasma levels, and hematocrit were not associated with the degree of FLOW regulation. In the present study only healthy subjects with laboratory values within relatively normal ranges were included, and we cannot exclude that FLOW regulation may be affected in patients with values far outside the normal range.…”