Neuroinflammation and neurodegeneration following blast traumatic brain injury

Roberts, Stuart Alexander Gordon ORCID: 0000-0002-6636-6326 (2021). Neuroinflammation and neurodegeneration following blast traumatic brain injury. University of Birmingham. Ph.D.

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Abstract

Blast traumatic brain injury (bTBI) is the signature injury from conflicts in Iraq and Afghanistan. Although chronic neuroinflammation has been detected following TBI, little is known about this following bTBI.

This thesis investigates TBI in UK military personnel before measuring neuroinflammation and neurodegeneration in personnel and an animal bTBI model.

Outcomes following TBI during those conflicts were analysed. This preceded a study involving ten personnel following bTBI. A single-centre MRS and [18F]GE180 PET case-control study assessed biomarkers of neuroinflammation. Furthermore, an animal bTBI model assessed immunohistochemical and neuroimaging markers of neuroinflammation and neurodegeneration.

Results showed survival improved year-on-year, except following severe TBI. Poor outcomes were driven by penetrating TBI. There were no significant changes related to neuroinflammation seen on MRS or PET, however the animal model demonstrated neuroinflammatory and neurodegenerative changes.

While improved survival rates endorse the success of the UK Defence Medical Services, there remains potential to improve outcomes following severe TBI in future conflicts. Multi-centre in vivo MRS and PET studies could be useful in detecting neuroinflammation but would require PET radioligands with improved VT. Ex vivo work validates DTI for detecting injury following bTBI, identifying areas for future study. Prognostication of poor outcome following TBI is no longer a self-fulfilling prophecy.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):