title: 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.
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.|School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK.
authors.forename: F D
authors.initials: FD
authors.lastname: McBryde
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: S C
authors.initials: SC
authors.lastname: Malpas
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.|School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK.
authors.forename: J F R
authors.initials: JF
authors.lastname: Paton
mesh_terms: D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007427:Intracranial Pressure / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology*
keywords: cerebral blood flow; cerebral perfusion; hypertension; intracranial pressure; ischaemic stroke; neural control of arterial pressure