Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults, characterized by primary and secondary injury. Primary injury is the immediate mechanical damage, while secondary injury results from delayed neuronal death, often linked to mitochondrial damage accumulation....
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MDPI AG
2023-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/12/2034 |
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| author | Reem Sakas Katya Dan Doron Edelman Saher Abu-Ata Aviv Ben-Menashe Yaseen Awad-Igbaria Jean Francois-Soustiel Eilam Palzur |
| author_facet | Reem Sakas Katya Dan Doron Edelman Saher Abu-Ata Aviv Ben-Menashe Yaseen Awad-Igbaria Jean Francois-Soustiel Eilam Palzur |
| author_sort | Reem Sakas |
| collection | DOAJ |
| description | Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults, characterized by primary and secondary injury. Primary injury is the immediate mechanical damage, while secondary injury results from delayed neuronal death, often linked to mitochondrial damage accumulation. Hyperbaric oxygen therapy (HBOT) has been proposed as a potential treatment for modulating secondary post-traumatic neuronal death. However, the specific molecular mechanism by which HBOT modulates secondary brain damage through mitochondrial protection remains unclear. Spatial learning, reference memory, and motor performance were measured in rats before and after Controlled Cortical Impact (CCI) injury. The HBOT (2.5 ATA) was performed 4 h following the CCI and twice daily (12 h intervals) for four consecutive days. Mitochondrial functions were assessed via high-resolution respirometry on day 5 following CCI. Moreover, IHC was performed at the end of the experiment to evaluate cortical apoptosis, neuronal survival, and glial activation. The current result indicates that HBOT exhibits a multi-level neuroprotective effect. Thus, we found that HBOT prevents cortical neuronal loss, reduces the apoptosis marker (cleaved-Caspase3), and modulates glial cell proliferation. Furthermore, HBO treatment prevents the reduction in mitochondrial respiration, including non-phosphorylation state, oxidative phosphorylation, and electron transfer capacity. Additionally, a superior motor and spatial learning performance level was observed in the CCI group treated with HBO compared to the CCI group. In conclusion, our findings demonstrate that HBOT during the critical period following the TBI improves cognitive and motor damage via regulating glial proliferation apoptosis and protecting mitochondrial function, consequently preventing cortex neuronal loss. |
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| id | doaj.art-fa7f01de6da44558a0ad7b8d0f4aeb98 |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-08T21:03:07Z |
| publishDate | 2023-11-01 |
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| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-fa7f01de6da44558a0ad7b8d0f4aeb982023-12-22T13:48:18ZengMDPI AGAntioxidants2076-39212023-11-011212203410.3390/antiox12122034Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in RatsReem Sakas0Katya Dan1Doron Edelman2Saher Abu-Ata3Aviv Ben-Menashe4Yaseen Awad-Igbaria5Jean Francois-Soustiel6Eilam Palzur7Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, IsraelAzrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, IsraelNeurosurgery Department, Tel-Aviv Sourasky Medical Center, Tel-Aviv 6423906, IsraelAzrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, IsraelAzrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, IsraelAzrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, IsraelAzrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, IsraelResearch Institute of Galilee Medical Center, Nahariya 221001, IsraelTraumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults, characterized by primary and secondary injury. Primary injury is the immediate mechanical damage, while secondary injury results from delayed neuronal death, often linked to mitochondrial damage accumulation. Hyperbaric oxygen therapy (HBOT) has been proposed as a potential treatment for modulating secondary post-traumatic neuronal death. However, the specific molecular mechanism by which HBOT modulates secondary brain damage through mitochondrial protection remains unclear. Spatial learning, reference memory, and motor performance were measured in rats before and after Controlled Cortical Impact (CCI) injury. The HBOT (2.5 ATA) was performed 4 h following the CCI and twice daily (12 h intervals) for four consecutive days. Mitochondrial functions were assessed via high-resolution respirometry on day 5 following CCI. Moreover, IHC was performed at the end of the experiment to evaluate cortical apoptosis, neuronal survival, and glial activation. The current result indicates that HBOT exhibits a multi-level neuroprotective effect. Thus, we found that HBOT prevents cortical neuronal loss, reduces the apoptosis marker (cleaved-Caspase3), and modulates glial cell proliferation. Furthermore, HBO treatment prevents the reduction in mitochondrial respiration, including non-phosphorylation state, oxidative phosphorylation, and electron transfer capacity. Additionally, a superior motor and spatial learning performance level was observed in the CCI group treated with HBO compared to the CCI group. In conclusion, our findings demonstrate that HBOT during the critical period following the TBI improves cognitive and motor damage via regulating glial proliferation apoptosis and protecting mitochondrial function, consequently preventing cortex neuronal loss.https://www.mdpi.com/2076-3921/12/12/2034traumatic brain injurysecondary brain injuryhyperbaric oxygen therapy (HBOT)apoptosismitochondria respiration |
| spellingShingle | Reem Sakas Katya Dan Doron Edelman Saher Abu-Ata Aviv Ben-Menashe Yaseen Awad-Igbaria Jean Francois-Soustiel Eilam Palzur Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats Antioxidants traumatic brain injury secondary brain injury hyperbaric oxygen therapy (HBOT) apoptosis mitochondria respiration |
| title | Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats |
| title_full | Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats |
| title_fullStr | Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats |
| title_full_unstemmed | Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats |
| title_short | Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats |
| title_sort | hyperbaric oxygen therapy alleviates memory and motor impairments following traumatic brain injury via the modulation of mitochondrial dysfunction induced neuronal apoptosis in rats |
| topic | traumatic brain injury secondary brain injury hyperbaric oxygen therapy (HBOT) apoptosis mitochondria respiration |
| url | https://www.mdpi.com/2076-3921/12/12/2034 |
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