The Expression of FOXO3a as a Forensic Diagnostic Tool in Cases of Traumatic Brain Injury: An Immunohistochemical Study

Author:

Maiese Aniello1,Spina Federica1ORCID,Visi Giacomo1ORCID,Del Duca Fabio2ORCID,De Matteis Alessandra2,La Russa Raffaele3ORCID,Di Paolo Marco1,Frati Paola2ORCID,Fineschi Vittorio2ORCID

Affiliation:

1. Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Section of Legal Medicine, University of Pisa, 56126 Pisa, Italy

2. Department of Anatomical, Histological, Forensic and Orthopedical Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy

3. Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy

Abstract

Traumatic brain injury (TBI) is one of the most well-known causes of neurological impairment and disability in the world. The Forkhead Box class O (FOXO) 3a is a transcription factor that is involved in different molecular processes, such as cell apoptosis regulation, neuroinflammation and the response to oxidative stress. This study is the first to evaluate the post-mortem immunohistochemical (IHC) positivity of FOXO3a expression in human cases of TBI deaths. The autopsy databases of the Legal Medicine and Forensic Institutes of the “Sapienza” University of Roma and the University of Pisa were retrospectively reviewed. After analyzing autopsy reports, 15 cases of TBI deaths were selected as the study group, while the other 15 cases were chosen among non-traumatic brain deaths as the control group. Decomposed bodies and those with initial signs of putrefaction were excluded. Routine histopathological studies were performed using hematoxylin–eosin (H&E) staining. Furthermore, an IHC investigation on cerebral samples was performed. To evaluate FOXO3a expression, anti-FOXO3a antibodies (GTX100277) were utilized. Concerning the IHC analysis, all 15 samples of TBI cases showed positivity for FOXO3a in the cerebral parenchyma. All control cerebral specimens showed FOXO3a negativity. In addition, the longer the survival time, the greater the positivity to the reaction with FOXO3a was. This study shows the important role of FOXO3a in neuronal autophagy and apoptosis regulation and suggests FOXO3a as a possible potential pharmacological target.

Funder

Sapienza University of Roma

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference47 articles.

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3. Centers for Disease Control and Prevention (2022, November 28). National Center for Health Statistics: Mortality Data on CDC WONDER, Available online: https://wonder.cdc.gov/mcd.html.

4. Traumatic brain injury: Estimate of the age of the injury based on neuroinflammation, endothelial activation markers and adhesion molecules;Maiese;Histol. Histopathol.,2021

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