Age and Sex Affect the Chronic Trajectory of Plasma Neurofilament Light and Glial Fibrillary Acidic Protein Levels in a Murine Thoracic Contusion Spinal Cord Injury Model.

Abstract

Background: Mouse models of traumatic spinal cord injury (SCI) are used to understand pathophysiology and test potential interventions. Experimental injury parameters, deficits on functional tasks, and histology are used to assess severity and recovery. Blood biomarkers may be a promising additional metric to assess severity and detect efficacy of interventions, but they have not been examined previously in mouse spinal cord injury (SCI).

Objectives: To examine blood biomarkers in mouse SCI.

Methods: We measured plasma levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) longitudinally following a thoracic contusion SCI in adolescent (3 month old) and aged (18 month old) male and female C57Bl6/J mice. Biomarkers were also assessed in comparably aged uninjured animals.

Results: Three-month-old animals exhibited elevated plasma NfL and GFAP 1 month after injury. NfL levels decreased from 1 to 2 months post injury but remained elevated from baseline, while GFAP levels remained high. Adolescent males exhibited higher NfL levels than females post injury. In aged animals, NfL was comparably elevated at 1 and 2 months post injury. In aged females, GFAP was elevated at 1 and 2 months after injury, while levels in males did not increase from baseline until 2 months after injury. Values from uninjured animals show plasma NfL and GFAP increase with age in absence of injury.

Conclusion: In a mouse SCI model, plasma NfL and GFAP are elevated chronically after injury. Sex and age at injury may affect biomarker trajectories, which may indicate underlying pathology relevant to treatment and recovery. Establishing the trajectory of NfL and GFAP after experimental injury may help to standardize injury paradigms, assess recovery, and detect efficacy of interventions.