Short-Term Cyclosporin A Treatment Reduced Serum Neurofilament-Light Levels in Diffuse but Not Focal Traumatic Brain Injury in a Piglet Model

<b>Background/Objectives</b>: Traumatic brain injury (TBI) in the pediatric patient results in acute neurophysiological deficits and can have potential long-term sequelae, impacting neurodevelopment. Serum biomarkers are an active area of study for TBI prognosis and diagnosis. Cyclosporin A (CsA), an immunosuppressant drug with neuroprotective qualities, targets mitochondria to stabilize the neurometabolic energy crisis following TBI. The objective of this study was to determine the acute effect of CsA treatment following focal and diffuse TBI on piglet serum biomarkers associated with glial neurofilaments, axonal dysfunction, and neuronal injury. <b>Methods</b>: Biomarker concentrations of GFAP, Nf-L, and UCH-L1 were quantified retrospectively from porcine serum samples (<i>n</i> = 488) at multiple timepoints from three experimental groups: anesthetized sham (<i>n</i> = 10), controlled cortical impact (CCI, <i>n</i> = 49), or rapid, non-impact rotations (RNR, <i>n</i> = 151) of the head. Injured animals received 24 h post-injury intravenous administration of saline or one of four CsA treatment doses (10, 20, 40, or 60 mg/kg/day), and then, were sacrificed. <b>Results</b>: After RNR, GFAP levels significantly increased from baseline at 1 h and recovered by 1 day to healthy reference ranges, while Nf-L increased at 1 day. Multiple CsA treatment doses (10, 40 mg/kg/day) significantly reduced Nf-L levels at 1 day compared to the untreated group. After CCI, GFAP and Nf-L increased at 1 day; there were no significant treatment effects. <b>Conclusions</b>: Focal and diffuse brain injury mechanisms resulted in distinct biomarker timelines. CsA reduced Nf-L levels at 1 day after diffuse TBI, showing promise of acute therapeutic benefit and warranting further investigation in extended timelines.