Version 1
: Received: 24 May 2024 / Approved: 27 May 2024 / Online: 27 May 2024 (11:21:54 CEST)
How to cite:
Hernandez, M.; Regan, S.; Ansari, R.; Logan-Wesley, A.; Lilova, R.; Levi, C.; Gorse, K.; Lafrenaye, A. The Effects of Cathepsin B Inhibition in the Face of Diffuse Traumatic Brain Injury and Secondary Intracranial Pressure Elevation. Preprints2024, 2024051740. https://doi.org/10.20944/preprints202405.1740.v1
Hernandez, M.; Regan, S.; Ansari, R.; Logan-Wesley, A.; Lilova, R.; Levi, C.; Gorse, K.; Lafrenaye, A. The Effects of Cathepsin B Inhibition in the Face of Diffuse Traumatic Brain Injury and Secondary Intracranial Pressure Elevation. Preprints 2024, 2024051740. https://doi.org/10.20944/preprints202405.1740.v1
Hernandez, M.; Regan, S.; Ansari, R.; Logan-Wesley, A.; Lilova, R.; Levi, C.; Gorse, K.; Lafrenaye, A. The Effects of Cathepsin B Inhibition in the Face of Diffuse Traumatic Brain Injury and Secondary Intracranial Pressure Elevation. Preprints2024, 2024051740. https://doi.org/10.20944/preprints202405.1740.v1
APA Style
Hernandez, M., Regan, S., Ansari, R., Logan-Wesley, A., Lilova, R., Levi, C., Gorse, K., & Lafrenaye, A. (2024). The Effects of Cathepsin B Inhibition in the Face of Diffuse Traumatic Brain Injury and Secondary Intracranial Pressure Elevation. Preprints. https://doi.org/10.20944/preprints202405.1740.v1
Chicago/Turabian Style
Hernandez, M., Karen Gorse and Audrey Lafrenaye. 2024 "The Effects of Cathepsin B Inhibition in the Face of Diffuse Traumatic Brain Injury and Secondary Intracranial Pressure Elevation" Preprints. https://doi.org/10.20944/preprints202405.1740.v1
Abstract
Traumatic brain injury (TBI) affects millions of people each year. Previous studies using the central fluid percussion injury (CFPI) model in adult male rats indicated that elevated intracranial pressure (ICP) was associated with long-term effects, including neuronal cell loss and increased sensory sensitivity post-injury and secondary ICP elevation, that were not seen following injury alone. Investigations also indicated that Cathepsin B (Cath B), a lysosomal cysteine protease, may play a role in the pathological progression of neuronal membrane disruption; however, the specific impact of Cath B inhibition following CFPI remains unknown. Thus, the focus of this study was to evaluate the effects of Cath B inhibition via intracerebroventricular infusion of CA-074Me 2w following injury with or without secondary elevation of ICP. This was accomplished using adult male rats continuously infused with CA-074Me or 10% DMSO as a vehicle control for 2w following either sham injury, a CFPI only, or a CFPI with subsequent ICP elevation to 20mmHg. We assessed Cath B activity in the lateral neocortices and liver, evaluated protein levels of Cath B and Cath B binding partners AIF, Bcl-XL, and Bak. We also conducted histological analyses of total cell counts to assess for cell loss, membrane disruption, and Cath B localization. Finally, we investigated somatosensory changes with the whisker nuisance task. Overall, this study demonstrated that Cath B is not a direct driver of membrane disruption, however, administration of CA-074Me alters Cath B localization and reduced hypersensitivity, emphasizing Cath B being an important component in late secondary pathologies.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
