The Expression of FOXO3a as a Forensic Diagnostic Tool in Cases of Traumatic Brain Injury: An Immunohistochemical Study.
Aniello MaieseFederica SpinaGiacomo VisiFabio Del DucaAlessandra De MatteisRaffaele La RussaMarco Di PaoloPaola FratiVittorio FineschiPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- transcription factor
- traumatic brain injury
- signaling pathway
- pi k akt
- oxidative stress
- poor prognosis
- dna binding
- cerebral ischemia
- subarachnoid hemorrhage
- endothelial cells
- multiple sclerosis
- binding protein
- spinal cord injury
- dna damage
- severe traumatic brain injury
- genome wide identification
- resting state
- endoplasmic reticulum stress
- functional connectivity
- lipopolysaccharide induced
- inflammatory response
- risk assessment
- human health
- heat stress
- climate change
- deep learning