Mechanisms of Cerebral Autoregulation in Traumatic Brain Injury
type: CreativeWork
description: While the last 30 years of research into the characterisation and dynamics of cerebral autoregulatory (CA) impairment has vastly improved understanding of this detrimental secondary injury process in traumatic brain injury (TBI), there are still unknowns before we can target autoregulatory disturbance in the neurocritical care unit. This thesis addresses two aspects of these unknowns: 1) CA in the previously uncharacterised paediatric TBI (pTBI) population, and 2) the underlying biochemical mechanisms of CA disturbance following adult TBI. There is a paucity of paediatric-specific data regarding the pressure reactivity index (PRx), with existing data limited to small or retrospective single centre studies. Studying Trends in AutoRegulation in Severe Head Injury in Paediatrics (STARSHIP) is the first multicentre prospective trial and aimed to characterise PRx in 135 children with pTBI. Firstly, I investigate the duration and magnitude of PRx disturbance following pTBI, and its association with outcome at 12 months post ictus. I demonstrate the potential clinical benefit of PRx monitoring in children, while showing that continuous measurement in the days following injury is worthwhile (Chapter 3). Next, I consider the applications of PRx monitoring in children, with the identification of the lower limit of autoregulation (LLA) in pTBI. I compare these findings to the cerebral perfusion guidelines suggested by the Brain Trauma Foundation and suggest possible clinical implications following the characterisation of this important index in children (Chapter 4). I then turn to adult TBI, where PRx is well understood and widely used. While we understand that PRx can advise treatment following TBI, we are currently unable to treat CA disturbance. To do so, researchers would need to understand the molecular basis of CA disturbance following brain injury. Guided by a literature review of candidate markers of CBF control following brain injury (Chapter 1), a large screen of 177…
abstract: While the last 30 years of research into the characterisation and dynamics of cerebral autoregulatory (CA) impairment has vastly improved understanding of this detrimental secondary injury process in traumatic brain injury (TBI), there are still unknowns before we can target autoregulatory disturbance in the neurocritical care unit. This thesis addresses two aspects of these unknowns: 1) CA in the previously uncharacterised paediatric TBI (pTBI) population, and 2) the underlying biochemical mechanisms of CA disturbance following adult TBI. There is a paucity of paediatric-specific data regarding the pressure reactivity index (PRx), with existing data limited to small or retrospective single centre studies. Studying Trends in AutoRegulation in Severe Head Injury in Paediatrics (STARSHIP) is the first multicentre prospective trial and aimed to characterise PRx in 135 children with pTBI. Firstly, I investigate the duration and magnitude of PRx disturbance following pTBI, and its association with outcome at 12 months post ictus. I demonstrate the potential clinical benefit of PRx monitoring in children, while showing that continuous measurement in the days following injury is worthwhile (Chapter 3). Next, I consider the applications of PRx monitoring in children, with the identification of the lower limit of autoregulation (LLA) in pTBI. I compare these findings to the cerebral perfusion guidelines suggested by the Brain Trauma Foundation and suggest possible clinical implications following the characterisation of this important index in children (Chapter 4). I then turn to adult TBI, where PRx is well understood and widely used. While we understand that PRx can advise treatment following TBI, we are currently unable to treat CA disturbance. To do so, researchers would need to understand the molecular basis of CA disturbance following brain injury. Guided by a literature review of candidate markers of CBF control following brain injury (Chapter 1), a large screen of 177…
author: Smith, Claudia Ann
language: eng
keywords: Traumatic brain injury, Cerebral autoregulation, Neuroinflammation, Paediatric brain injury, Critical care, Pressure reactivity
license: https://www.repository.cam.ac.uk/bitstreams/8699678f-8657-439a-b282-8aa946129614/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2025-04-03
date modified: 2026-07-22T22:24:24Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.121860