Folia Neuropathologica (Mar 2021)

Elevated serum and urine levels of progranulin (PGRN) as a predictor of microglia activation in the early phase of traumatic brain injury: a further link with the development of neurodegenerative diseases

  • Mieszko Olczak,
  • Łukasz A. Poniatowski,
  • Agnieszka Siwińska,
  • Magdalena Kwiatkowska,
  • Dominik Chutorański,
  • Teresa Wierzba-Bobrowicz

DOI
https://doi.org/10.5114/fn.2021.105137
Journal volume & issue
Vol. 59, no. 1
pp. 81 – 90

Abstract

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Traumatic brain injury (TBI) is a frequent finding during forensic autopsies and neuropathological examinations in medico-legal practices. Despite the unprecedented attention currently focused on TBI pathogenesis, there is a need to improve its diagnostics through the use of novel biomarkers to facilitate detection, treatment, and prognosis. Recently, growth factor progranulin (PGRN) has attracted significant attention because of its neurotrophic and anti-inflammatory activities. The role of PGRN in TBI has not been widely discussed, although PGRN-related neuroinflammatory and neurodegenerative phenomena have been described. The aim of this study was to identify PGRN concentration levels in biofluids and examine PGRN and CD68 protein expression in brain tissue using immunohistochemical staining in individuals with fatal TBI in its early phase. The study was performed using cases (n = 30) of fatal head injury and control cases (n = 30) of sudden death. The serum and urine were collected within ~24 h after death and compared using the ELISA test, where brain specimens were stained with anti-PGRN and anti-CD68 antibodies. In our study, we observed elevated concentration levels of PGRN in the serum and urine of TBI individuals in the early phase of TBI. These changes were accompanied by increased expression of PGRN in the frontal cortex (1st-3rd layers), in which anti-CD68 immunostaining revealed disseminated cortical microglia activation. The possible implementation of performing such assays offers a novel and interesting tool for investigation and research regarding TBI diagnosis and pathogenesis. Furthermore, the above-mentioned surrogate biofluid assays may be useful in clinical prognosis and risk calculation of non-fatal cases of TBI, considering the development of neurodegenerative conditions of TBI individuals.

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