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B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective.
- Source :
-
Medicina (Kaunas, Lithuania) [Medicina (Kaunas)] 2020 Jun 18; Vol. 56 (6). Date of Electronic Publication: 2020 Jun 18. - Publication Year :
- 2020
-
Abstract
- Background and Objectives: The injury burden after head trauma is exacerbated by secondary sequelae, which leads to further neuronal loss. B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic protein and a key modulator of the programmed cell death (PCD) pathways. The current study evaluates the clinical evidence on Bcl-2 and neurological recovery in patients after traumatic brain injury (TBI). Materials and Methods: All studies in English were queried from the National Library of Medicine PubMed database using the following search terms: (B-cell lymphoma 2/Bcl-2/Bcl2) AND (brain injury/head injury/head trauma/traumatic brain injury) AND (human/patient/subject). There were 10 investigations conducted on Bcl-2 and apoptosis in TBI patients, of which 5 analyzed the pericontutional brain tissue obtained from surgical decompression, 4 studied Bcl-2 expression as a biomarker in the cerebrospinal fluid (CSF), and 1 was a prospective randomized trial. Results: Immunohistochemistry (IHC) in 94 adults with severe TBI showed upregulation of Bcl-2 in the pericontusional tissue. Bcl-2 was detected in 36-75% of TBI patients, while it was generally absent in the non-TBI controls, with Bcl-2 expression increased 2.9- to 17-fold in TBI patients. Terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick-end labeling (TUNEL) positivity for cell death was detected in 33-73% of TBI patients. CSF analysis in 113 TBI subjects (90 adults, 23 pediatric patients) showed upregulation of Bcl-2 that peaked on post-injury day 3 and subsequently declined after day 5. Increased Bcl-2 in the peritraumatic tissue, rising CSF Bcl-2 levels, and the variant allele of rs17759659 are associated with improved mortality and better outcomes on the Glasgow Outcome Score (GOS). Conclusions: Bcl-2 is upregulated in the pericontusional brain and CSF in the acute period after TBI. Bcl-2 has a neuroprotective role as a pro-survival protein in experimental models, and increased expression in patients can contribute to improvement in clinical outcomes. Its utility as a biomarker and therapeutic target to block neuronal apoptosis after TBI warrants further evaluation.
- Subjects :
- Biomarkers analysis
Biomarkers cerebrospinal fluid
Brain Injuries, Traumatic cerebrospinal fluid
Brain Injuries, Traumatic physiopathology
Humans
Lymphoma, B-Cell physiopathology
Proto-Oncogene Proteins c-bcl-2 analysis
Proto-Oncogene Proteins c-bcl-2 cerebrospinal fluid
Apoptosis physiology
Brain Injuries, Traumatic complications
Lymphoma, B-Cell cerebrospinal fluid
Subjects
Details
- Language :
- English
- ISSN :
- 1648-9144
- Volume :
- 56
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Medicina (Kaunas, Lithuania)
- Publication Type :
- Academic Journal
- Accession number :
- 32570722
- Full Text :
- https://doi.org/10.3390/medicina56060300