Examining the consequences of sPLA2 inhibition following traumatic brain injury
Year: 2011
Type: dissertation
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.
DOI: 10.17918/etd-3464
Authors: Angel Lucena, Aleister Saunders
Institutions: University of Dhaka, Drexel University
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4205651028