Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway
Abstract Background Studies have confirmed the salutary effects of progesterone (P4) on traumatic brain injury (TBI). This study investigated the beneficial effects of P4 via its receptors on TBI, and also whether progesterone receptors (PRs) can modulate TBI through PI3K/Akt pathway. Material and m...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.3244 |
| _version_ | 1797632584966995968 |
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| author | Ladan Amirkhosravi Mohammad khaksari Sedigheh Amiresmaili Mojgan Sanjari Parisa Khorasani Morteza Hashemian |
| author_facet | Ladan Amirkhosravi Mohammad khaksari Sedigheh Amiresmaili Mojgan Sanjari Parisa Khorasani Morteza Hashemian |
| author_sort | Ladan Amirkhosravi |
| collection | DOAJ |
| description | Abstract Background Studies have confirmed the salutary effects of progesterone (P4) on traumatic brain injury (TBI). This study investigated the beneficial effects of P4 via its receptors on TBI, and also whether progesterone receptors (PRs) can modulate TBI through PI3K/Akt pathway. Material and methods Marmarou method was utilized to induce diffuse TBI in ovariectomized rats. P4 (1.7 mg/kg) or the vehicle (oil) was administered 30 min after TBI induction. Moreover, RU486 (PR antagonist) and its vehicle (DMSO) were injected before TBI induction and P4 injection. Brain Evans blue content, brain water content (WC), various oxidative stress parameters, IL‐1β levels, tumor necrosis factor‐α (TNF‐α), histopathological alterations, and also phosphorylated Akt (p‐Akt) and PI3K expressions in the brain were assessed 24 h after TBI. The veterinary comma scale (VCS) was measured before and after TBI at different times. Results The findings revealed that P4 caused an increase in VCS and a decrease in brain WC, oxidative stress, TNF‐α and IL‐1β levels. RU486 inhibited the beneficial effects of P4 on these indices. Moreover, RU486 prevented the reduction of brain edema, inflammation, and apoptosis caused by P4. Moreover, P4 following TBI increased the expression of PI3K/p‐Akt protein in the brain. RU486 eliminated the effects of P4 on PI3K/p‐Akt expression. Conclusion According to these findings, PRs are acting as critical mediators for the neuroprotective properties of P4 on oxidative stress, pro‐inflammatory cytokine levels, and neurological outcomes. PRs also play an important role in regulating the PI3K/p‐Akt expression and nongenomic function of P4. |
| first_indexed | 2024-03-11T11:39:57Z |
| format | Article |
| id | doaj.art-c94c6ebd6b924366a8d7516beb12afc1 |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-03-11T11:39:57Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-c94c6ebd6b924366a8d7516beb12afc12023-11-10T06:53:59ZengWileyBrain and Behavior2162-32792023-11-011311n/an/a10.1002/brb3.3244Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathwayLadan Amirkhosravi0Mohammad khaksari1Sedigheh Amiresmaili2Mojgan Sanjari3Parisa Khorasani4Morteza Hashemian5Endocrinology and Metabolism Research Center Institute of Basic and Clinical Physiology Sciences Kerman University of Medical Sciences Kerman IranPhysiology Research Center Institute of Neuropharmacology Kerman University of Medical Sciences Kerman IranDepartment of Physiology Bam University of Medical Sciences Bam IranEndocrinology and Metabolism Research Center Institute of Basic and Clinical Physiology Sciences Kerman University of Medical Sciences Kerman IranDepartment of Pathology, Pathology, and Stem Cells Research Center, Afzalipour Medical Faculty Kerman University of Medical Sciences Kerman IranNeuroscience Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman IranAbstract Background Studies have confirmed the salutary effects of progesterone (P4) on traumatic brain injury (TBI). This study investigated the beneficial effects of P4 via its receptors on TBI, and also whether progesterone receptors (PRs) can modulate TBI through PI3K/Akt pathway. Material and methods Marmarou method was utilized to induce diffuse TBI in ovariectomized rats. P4 (1.7 mg/kg) or the vehicle (oil) was administered 30 min after TBI induction. Moreover, RU486 (PR antagonist) and its vehicle (DMSO) were injected before TBI induction and P4 injection. Brain Evans blue content, brain water content (WC), various oxidative stress parameters, IL‐1β levels, tumor necrosis factor‐α (TNF‐α), histopathological alterations, and also phosphorylated Akt (p‐Akt) and PI3K expressions in the brain were assessed 24 h after TBI. The veterinary comma scale (VCS) was measured before and after TBI at different times. Results The findings revealed that P4 caused an increase in VCS and a decrease in brain WC, oxidative stress, TNF‐α and IL‐1β levels. RU486 inhibited the beneficial effects of P4 on these indices. Moreover, RU486 prevented the reduction of brain edema, inflammation, and apoptosis caused by P4. Moreover, P4 following TBI increased the expression of PI3K/p‐Akt protein in the brain. RU486 eliminated the effects of P4 on PI3K/p‐Akt expression. Conclusion According to these findings, PRs are acting as critical mediators for the neuroprotective properties of P4 on oxidative stress, pro‐inflammatory cytokine levels, and neurological outcomes. PRs also play an important role in regulating the PI3K/p‐Akt expression and nongenomic function of P4.https://doi.org/10.1002/brb3.3244neuroprotectionoxidative stressPI3K/p‐Aktprogesterone receptorpro‐inflammatory cytokinestraumatic brain injury |
| spellingShingle | Ladan Amirkhosravi Mohammad khaksari Sedigheh Amiresmaili Mojgan Sanjari Parisa Khorasani Morteza Hashemian Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway Brain and Behavior neuroprotection oxidative stress PI3K/p‐Akt progesterone receptor pro‐inflammatory cytokines traumatic brain injury |
| title | Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway |
| title_full | Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway |
| title_fullStr | Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway |
| title_full_unstemmed | Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway |
| title_short | Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway |
| title_sort | evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury the pi3k akt pathway |
| topic | neuroprotection oxidative stress PI3K/p‐Akt progesterone receptor pro‐inflammatory cytokines traumatic brain injury |
| url | https://doi.org/10.1002/brb3.3244 |
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