Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Dissertation
Examining the consequences of sPLA2 inhibition following traumatic brain injury
Doctor of Philosophy (Ph.D.), Drexel University
Mar 2011
DOI:
https://doi.org/10.17918/etd-3464
Abstract
Neuroinflammation is in found in parallel with nearly all acute and chronic neurodegenerative insults including: traumatic brain injury (TBI), spinal cord injury (SCI), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Neuroinflammation is responsible for most of the secondary damage that occurs within region of the insult including the formation of cavities and cysts that inhibit neuronal growth. Promising targets include secreted phospholipase-A2 enzymes (sPLA2) given that they are up-regulated following neurodegenerative insults and liberate lysolipids and fatty acids which initiate pro-inflammatory cascades. In the following body of work we outline the anatomical and molecular consequences of sPLA2 inhibition following traumatic brain injury. Systemic treatment with an uncompetitive sPLA2 inhibitor (CHEC-9) reduced sPLA2 activity the injury site leading to neuroprotection via the following mechanisms; 1) reducing phospholipid breakdown (and PLA2 products), 2) diminishing ceramide generation, 3) inhibiting activation of microglia/macrophages in the injury site and 4) reducing apoptosis-resulting in a significant reduction in neuronal degeneration.
Metrics
35 File views/ downloads
36 Record Views
Details
- Title
- Examining the consequences of sPLA2 inhibition following traumatic brain injury
- Creators
- Angel Lucena - DU
- Contributors
- Aleister Saunders (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 3464; 991014632241504721