B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective
<i>Background and Objectives:</i> 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 eval...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1010-660X/56/6/300 |
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| author | Hansen Deng John K. Yue Benjamin E. Zusman Enyinna L. Nwachuku Hussam Abou-Al-Shaar Pavan S. Upadhyayula David O. Okonkwo Ava M. Puccio |
| author_facet | Hansen Deng John K. Yue Benjamin E. Zusman Enyinna L. Nwachuku Hussam Abou-Al-Shaar Pavan S. Upadhyayula David O. Okonkwo Ava M. Puccio |
| author_sort | Hansen Deng |
| collection | DOAJ |
| description | <i>Background and Objectives:</i> 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). <i>Materials and Methods:</i> 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. <i>Results:</i> 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 <i>rs17759659</i> are associated with improved mortality and better outcomes on the Glasgow Outcome Score (GOS). <i>Conclusions:</i> 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. |
| first_indexed | 2024-03-12T09:06:34Z |
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| language | English |
| last_indexed | 2024-03-12T09:06:34Z |
| publishDate | 2020-06-01 |
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| spelling | doaj.art-479ed1eeeec2433ab2aa584c7b5d13b22023-09-02T15:16:00ZengMDPI AGMedicina1010-660X2020-06-015630030010.3390/medicina56060300B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical PerspectiveHansen Deng0John K. Yue1Benjamin E. Zusman2Enyinna L. Nwachuku3Hussam Abou-Al-Shaar4Pavan S. Upadhyayula5David O. Okonkwo6Ava M. Puccio7Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USADepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USADepartment of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USADepartment of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USADepartment of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USADepartment of Neurological Surgery, University of California Diego, San Diego, CA 92093, USADepartment of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USADepartment of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA<i>Background and Objectives:</i> 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). <i>Materials and Methods:</i> 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. <i>Results:</i> 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 <i>rs17759659</i> are associated with improved mortality and better outcomes on the Glasgow Outcome Score (GOS). <i>Conclusions:</i> 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.https://www.mdpi.com/1010-660X/56/6/300Bcl-2BaxBcl-x<sub>L</sub>apoptosisprogrammed cell deathtraumatic brain injury |
| spellingShingle | Hansen Deng John K. Yue Benjamin E. Zusman Enyinna L. Nwachuku Hussam Abou-Al-Shaar Pavan S. Upadhyayula David O. Okonkwo Ava M. Puccio B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective Medicina Bcl-2 Bax Bcl-x<sub>L</sub> apoptosis programmed cell death traumatic brain injury |
| title | B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective |
| title_full | B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective |
| title_fullStr | B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective |
| title_full_unstemmed | B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective |
| title_short | B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective |
| title_sort | b cell lymphoma 2 bcl 2 and regulation of apoptosis after traumatic brain injury a clinical perspective |
| topic | Bcl-2 Bax Bcl-x<sub>L</sub> apoptosis programmed cell death traumatic brain injury |
| url | https://www.mdpi.com/1010-660X/56/6/300 |
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