Primary Blast-Induced Traumatic Brain Injury in Rats Leads to Increased Prion Protein in Plasma: A Potential Biomarker for Blast-Induced Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is deemed the ''signature injury'' of recent military conflicts in Afghanistan and Iraq, largely because of increased blast exposure. Injuries to the brain can often be misdiagnosed, leading to further complications in the future. Therefore, the use of protein biomarkers for the screening and diagnosis of TBI is urgently needed. In the present study, we have investigated the plasma levels of soluble cellular prion protein (PrPC) as a novel biomarker for the diagnosis of primary blast-induced TBI (bTBI). We hypothesize that the primary blast wave can disrupt the brain and dislodge extracellular localized PrPC, leading to a rise in concentration within the systemic circulation. Adult male Sprague-Dawley rats were exposed to single pulse shockwave overpressures of varying intensities (15-30 psi or 103.4-206.8 kPa] using an advanced blast simulator. Blood plasma was collected 24 h after insult, and PrPC concentration was determined with a modified commercial enzyme-linked immunosorbent assay (ELISA) specific for PrPC. We provide the first report that mean PrPC concentration in primary blast exposed rats (3.97 ng/mL -0.13 SE) is significantly increased compared with controls (2.46 ng/mL -0.14 SE; two tailed test p < 0.0001). Furthermore, we report a mild positive rank correlation between PrPC concentration and increasing blast intensity (psi) reflecting a plateaued response at higher pressure magnitudes, which may have implications for all military service members exposed to blast events. In conclusion, it appears that plasma levels of PrPC may be a novel biomarker for the detection of primary bTBI.

Biomarkers in traumatic brain injury: a review

“…A recent study suggested a potential biomarker specific to blast TBI—soluble cellular prion protein (PrPC). The hypothesis is that the primary blast wave can dislodge any extracellular PrPC and lead to a systemic rise in its concentration 65. The hypothesis was demonstrable in rat models in a 2015 study and the authors concluded the PrPC could be a novel biomarker for detection of primary blast TBI in military personnel.…”

The current state of biomarkers of mild traumatic brain injury

“…Because PrP c is located entirely within the extracellular domain of the plasma membrane, it is reasonable to suspect that it may be released during a concussive event through BBB disruption (33). Indeed, transcription of the prion protein gene (PRNP) is upregulated in a rat model of concussion following blast exposure, resulting in increased serum levels (34,35).…”

Vascular and non‐vascular contributors to memory reduction during traumatic brain injury

“…It has been shown that PrP C is increased in blood during TBI (Pham, Akonasu, Shishkin, & Taghibiglou, ; Pham, Sawyer, et al., ). Therefore, formation of PrP C aggregates in extravascular space during TBI can be a result of leaking of this plasma protein through the impaired vascular wall.…”