Vascular and cellular responses to traumatic brain injury

Hay, Jennifer R. (2018) Vascular and cellular responses to traumatic brain injury. PhD thesis, University of Glasgow.

Abstract

There is growing evidence that suggests Traumatic brain injury (TBI) may initiate long-term neurodegenerative processes. Exposure to a single moderate or severe TBI, or to repetitive TBI, reveals a complex of pathologies including abnormalities of tau, amyloid-β and TDP-43; neuronal loss; neuroinflammation; and white matter degradation. The mechanisms driving these late post-TBI neurodegenerative pathologies remain elusive.
Firstly, a potential association between blood-brain barrier (BBB) disruption and TBI was investigated. Results showed that increased and widespread BBB disruption was observed in material from patients dying in the acute phase following a single, moderate to severe TBI and persisted in a high proportion of patients surviving years following injury. Furthermore, there was preferential distribution to the deep layers of the cortex and to the crests of the gyri rather than the depths of the sulci. This post-TBI BBB disruption was investigated further within a paediatric TBI cohort. BBB disruption was noted in both paediatric and adult TBI in a similar pattern and distribution, however, interestingly, in sharp contrast to adult TBI cases, BBB disruption in paediatric cases appears preferentially distributed to capillary sized vessels. This vulnerability of the small vessels was rarely observed in adult material.
In addition to the post-TBI vascular change observed, the cellular response was investigated, which interestingly, demonstrated regional differences. Specifically, in the grey matter, reactive astrogliosis was observed subpially, around cortical vessels, at the grey and white matter boundaries and subependymally. This astrogliosis was evident in a proportion of acute and continued into the late phase following TBI. In contrast, microglial activation was observed as a delayed response and localised to the white matter tracts. In addition, this delayed microglial response expressed an M2-like phenotype. Furthermore, there was an increased population of inactivated perivascular microglia beyond the perivascular space in the grey matter regions, observed in the acute phase and persisted in a proportion of patients surviving years following injury. Collectively these findings are interesting and indicate TBI induces both a vascular and cellular responses which may contribute to the long-term post-TBI neurodegenerative processes.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Introduction (Chapter 1) Published, Hay J, Johnson VE, Smith DH, Stewart W. Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury. Annual review of pathology. 2016;11:21-45. doi:10.1146/annurev-pathol-012615-044116. Chapter 3 Published, Hay JR, Johnson VE, Young AM, Smith DH, Stewart W. Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans. J Neuropathol Exp Neurol. 2015 Dec;74(12):1147-57. doi: 10.1097/NEN.0000000000000261.
• Keywords: Traumatic brain injury, blood-brain barrier, chronic traumatic encephalopathy, astrocytes, microglia.
• Subjects: R Medicine > RB Pathology; R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Supervisor's Name: Stewart, Dr. William and Cavanagh, Professor Jonathan
• Date of Award: 2018
• Depositing User: Ms Jennifer R Hay
• Unique ID: glathesis:2018-30819
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 03 Oct 2018 10:35
• Last Modified: 03 Oct 2018 11:05
• URI: https://theses.gla.ac.uk/id/eprint/30819

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