THE ROLE OF LYSOSOMAL DYSREGULATION IN TRAUMATIC BRAIN INJURY-INDUCED NEURODEGENERATION

Traumatic brain injury (TBI)-induced Wallerian degeneration and secondary injury sequelae are associated with persisting neuroinflammation hypothesized to increase risk or early-onset of neurodegenerative diseases. At 6-months post-midline fluid percussion injury (FPI) in a rodent model of TBI, we evaluated markers of neuropathology (amino cupric-silver stain), axonal injury (APP), neuroinflammation (ionized calcium binding adaptor molecule, Iba-1), autophagy (neutral red), phospho-tau (AT8), macrophage recruitment (CD68), and lysosome (LAMP-1) pathology in the dentate gyrus (DG) of the hippocampus in male and female Sprague Dawley rats (n=5-6/group). Positive silver staining was present in injured and age-matched shams; however, the organization, localization, and degree of neuropathology differed within the regions of the DG. A 45% increase in neutral red staining pixel density was present in injured rats compared to sham (p<0.05). No AT8 staining was present in the DG or observed in other brain regions. No quantifiable sex differences were detected. Differential distribution of neuropathology and evidence of persistently activated autophagy pathways implicate novel differences between age-related and injury-related neuropathological processes that require further investigation.