Exploration of post-blast neuropathology and the use of a promising fluid biomarker in a rat model of blast traumatic brain injury
File(s)
Author(s)
May, Hazel
Type
Thesis
Abstract
Blast traumatic brain injury (bTBI) poses significant challenges for military and civilian populations, leading to a wide range of short and long-term morbidities. Detecting brain damage in mild bTBI is challenging and understanding the causes of the morbidities remains unclear, requiring further investigation into bTBI pathology and the development of more sensitive diagnostic tools.
This thesis investigates the underlying neuropathological alterations behind electrophysiological abnormalities observed in bTBI and the sensitivity of a promising fluid biomarker for TBI that detects diffuse axonal injury (DAI). To achieve this, I optimised a rodent model of mild primary bTBI to conduct electrophysiological, histological, and fluid biomarker analyses at different times post-injury. Electrophysiological analysis revealed a hallmark power increases in the lower frequency bands at 1 and 3 months after injury. To understand the association between electrophysiological changes and bTBI, inhibitory GABAergic interneuronal densities were examined. Results revealed a decrease in interneuronal densities at 7 days, 1 month, and 3 months post-injury, indicating a connection between excitation, inhibition, and the observed electrophysiological alterations. These alterations were paralleled with increases in microglial density at early points post-injury and elevations in microglia size at 3 months post-injury. Additionally, DAI in the white matter, determined by increased immunofluorescent intensity staining of neurofilament light (NFL) in the corpus callosum at 7 days and 1 month post-injury, may have also contributed to these electrophysiological changes...
This thesis investigates the underlying neuropathological alterations behind electrophysiological abnormalities observed in bTBI and the sensitivity of a promising fluid biomarker for TBI that detects diffuse axonal injury (DAI). To achieve this, I optimised a rodent model of mild primary bTBI to conduct electrophysiological, histological, and fluid biomarker analyses at different times post-injury. Electrophysiological analysis revealed a hallmark power increases in the lower frequency bands at 1 and 3 months after injury. To understand the association between electrophysiological changes and bTBI, inhibitory GABAergic interneuronal densities were examined. Results revealed a decrease in interneuronal densities at 7 days, 1 month, and 3 months post-injury, indicating a connection between excitation, inhibition, and the observed electrophysiological alterations. These alterations were paralleled with increases in microglial density at early points post-injury and elevations in microglia size at 3 months post-injury. Additionally, DAI in the white matter, determined by increased immunofluorescent intensity staining of neurofilament light (NFL) in the corpus callosum at 7 days and 1 month post-injury, may have also contributed to these electrophysiological changes...
Version
Open Access
Date Issued
2023-06-28
Date Awarded
01/10/2023
License URL
Advisor
Sharp, David
Sastre, Magdalena
Ghajari, Mazdak
Sponsor
Centre of Blast Injury Studies
Publisher Department
Department of Brain Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)