Sindhura Sridhar

Introduction. Pediatric traumatic brain injury (pTBI) is the leading cause of death and disability in children, impacting 475,000 children in the US between the ages 0-14 annually¹. Children who experience at least one traumatic brain injury (TBI) are at risk for developing long-term physical, cognitive, and psychological consequences². Nearly 20% of pTBI patients have complications that are undiagnosed because they do not present on imaging or do not present with obvious symptoms³. Currently, there are no established biomarkers to assess pTBI⁴. Osteopontin (OPN) is a phosphoglycoprotein that is expressed in immune cells throughout the body and is an inflammatory cytokine inducer^4,5. Osteopontin is upregulated in macrophages and activated microglia in response to various brain pathologies^4,5. This suggests that OPN could be a valuable biomarker to evaluate pTBI. Methods. Head stab wounds were inflicted on WT and OPN/KO mice^5,6. Lesioned tissue was examined over a period of 28 days with in situ hybridization and immunofluorescent staining^5,6. OPN expression and activation was quantified using anti-BrdU antibodies^5,6. Controlled cortical impact (CCI) models were developed using juvenile mice; plasma samples were also taken from pTBI patients⁴. Levels of GFAP, MMP-9, and OPN in the CCI models and pTBI plasma samples were quantified and comparative statistical analysis was performed⁴. Results. Osteopontin was expressed in astrocytes, microglial cells, and in damaged neurites; it was not found in healthy tissue⁶. Increased incorporation of BrdU in WT mice was associated with increased activation of glial cells and immunofluorescent staining showed OPN enhancement and direction of astrocyte and microglial phagocytosis within lesioned tissue^5,6. OPN was found to be upregulated in response to acute pTBI⁴. OPN was also shown to correlate with injury severity and indicators of prognosis, such as imaging findings, days in ICU, and mortality⁴. OPN vastly outperformed similar inflammatory molecules such as GFAP and MMP-9 in both assessment of injury severity and prognosis⁴. Conclusion. Osteopontin shows potential as an inflammatory biomarker that has specific correlations with pTBI. OPN is found in large quantities in the blood and brain tissue post-injury and plays a key role in the initial repair of lesioned brain tissue. OPN can both confirm that TBI has occurred and predict long-term outcomes for pTBI patients. The results above indicate that plasma OPN analysis could be a low-cost and effective addition to traditional imaging and screening protocols for pTBI patients.

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