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Updated: Jul 31, 2025
Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
Candidate neuroinflammatory markers of cerebral autoregulation dysfunction in human acute brain injury
Claudia A Smith1, Keri Lh Carpenter1, Peter J Hutchinson1
1Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Insights
Impaired cerebral autoregulation (CA) after brain injury is common but poorly understood. This review explores neuroinflammation and vascular dysfunction as potential causes of CA impairment, aiming to improve patient outcomes.
Area of Science:
- Neuroscience
- Neurology
- Critical Care Medicine
Background:
- Loss of cerebral autoregulation (CA) is a significant secondary injury after acute brain injury, linked to poor outcomes.
- Current CA-directed therapies modifying cerebral perfusion pressure (CPP) targets show limited proven benefit.
- Underlying mechanisms and triggers of CA impairment beyond CPP are largely unknown.
Purpose of the Study:
- To review the impairment of CA following acute brain injury.
- To explore neuroinflammation and cerebral vascular disturbances as potential mechanisms for CA dysfunction.
- To identify candidate vascular and endothelial markers linked to cerebral blood flow (CBF) and autoregulation disturbances.
Main Methods:
- Literature review focusing on CA, its impairment, and associated mechanisms.
- Discussion of neuroinflammation, vascular, and endothelial markers.
- Analysis of evidence from human traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH), with supporting animal data.
Main Results:
- CA impairment is a common complication of acute brain injury.
- Neuroinflammation affecting cerebral vasculature is a potential mechanism causing CA dysfunction.
- Candidate vascular and endothelial markers are discussed in relation to CBF and autoregulation.
Conclusions:
- Understanding the mechanisms of CA dysfunction, particularly neuroinflammation, is crucial for improving therapeutic strategies.
- Further research into vascular and endothelial markers may lead to better management of CA following brain injury.
- This review provides a foundation for investigating novel CA-directed therapies in TBI, SAH, and other neurological conditions.
Abstract:
The loss of cerebral autoregulation (CA) is a common and detrimental secondary injury mechanism following acute brain injury and has been associated with worse morbidity and mortality. However patient outcomes have not as yet been conclusively proven to have improved as a result of CA-directed therapy. While CA monitoring has been used to modify CPP targets, this approach cannot work if the impairment of CA is not simply related to CPP but involves other underlying mechanisms and triggers, which at present are largely unknown. Neuroinflammation, particularly inflammation affecting the cerebral vasculature, is an important cascade that occurs following acute injury. We hypothesise that disturbances to the cerebral vasculature can affect the regulation of CBF, and hence the vascular inflammatory pathways could be a putative mechanism that causes CA dysfunction. This review provides a brief overview of CA, and its impairment following brain injury. We discuss candidate vascular and endothelial markers and what is known about their link to disturbance of the CBF and autoregulation. We focus on human traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH), with supporting evidence from animal work and applicability to wider neurologic diseases.
