Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury
IntroductionTraumatic brain injury (TBI) is a leading cause of disability in the US. Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) to inhibit inflammatory mediators and decrease reactive oxygen species within the CNS. Few studies have identifie...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Behavioral Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2022.903980/full |
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| author | Ryan P. Bruhns Maha Ibrahim Sulaiman Michael Gaub Esther H. Bae Rachel B. Davidson Knapp Anna R. Larson Angela Smith Deziree L. Coleman William D. Staatz Alexander J. Sandweiss Bellal Joseph Meredith Hay Tally M. Largent-Milnes Todd W. Vanderah |
| author_facet | Ryan P. Bruhns Maha Ibrahim Sulaiman Michael Gaub Esther H. Bae Rachel B. Davidson Knapp Anna R. Larson Angela Smith Deziree L. Coleman William D. Staatz Alexander J. Sandweiss Bellal Joseph Meredith Hay Tally M. Largent-Milnes Todd W. Vanderah |
| author_sort | Ryan P. Bruhns |
| collection | DOAJ |
| description | IntroductionTraumatic brain injury (TBI) is a leading cause of disability in the US. Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) to inhibit inflammatory mediators and decrease reactive oxygen species within the CNS. Few studies have identified whether Ang-(1-7) decreases cognitive impairment following closed TBI. This study examined the therapeutic effect of Ang-(1-7) on secondary injury observed in a murine model of mild TBI (mTBI) in a closed skull, single injury model.Materials and methodsMale mice (n = 108) underwent a closed skull, controlled cortical impact injury. Two hours after injury, mice were administered either Ang-(1-7) (n = 12) or vehicle (n = 12), continuing through day 5 post-TBI, and tested for cognitive impairment on days 1–5 and 18. pTau, Tau, GFAP, and serum cytokines were measured at multiple time points. Animals were observed daily for cognition and motor coordination via novel object recognition. Brain sections were stained and evaluated for neuronal injury.ResultsAdministration of Ang-(1-7) daily for 5 days post-mTBI significantly increased cognitive function as compared to saline control-treated animals. Cortical and hippocampal structures showed less damage in the presence of Ang-(1-7), while Ang-(1-7) administration significantly changed the expression of pTau and GFAP in cortical and hippocampal regions as compared to control.DiscussionThese are among the first studies to demonstrate that sustained administration of Ang-(1-7) following a closed-skull, single impact mTBI significantly improves neurologic outcomes, potentially offering a novel therapeutic modality for the prevention of long-term CNS impairment following such injuries. |
| first_indexed | 2024-04-12T07:59:54Z |
| format | Article |
| id | doaj.art-8d2363e03db44e41afd84e454813225b |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-12T07:59:54Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-8d2363e03db44e41afd84e454813225b2022-12-22T03:41:20ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532022-08-011610.3389/fnbeh.2022.903980903980Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injuryRyan P. Bruhns0Maha Ibrahim Sulaiman1Michael Gaub2Esther H. Bae3Rachel B. Davidson Knapp4Anna R. Larson5Angela Smith6Deziree L. Coleman7William D. Staatz8Alexander J. Sandweiss9Bellal Joseph10Meredith Hay11Tally M. Largent-Milnes12Todd W. Vanderah13Department of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Surgery, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Physiology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, College of Medicine and Health Sciences, University of Arizona, Tucson, AZ, United StatesIntroductionTraumatic brain injury (TBI) is a leading cause of disability in the US. Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) to inhibit inflammatory mediators and decrease reactive oxygen species within the CNS. Few studies have identified whether Ang-(1-7) decreases cognitive impairment following closed TBI. This study examined the therapeutic effect of Ang-(1-7) on secondary injury observed in a murine model of mild TBI (mTBI) in a closed skull, single injury model.Materials and methodsMale mice (n = 108) underwent a closed skull, controlled cortical impact injury. Two hours after injury, mice were administered either Ang-(1-7) (n = 12) or vehicle (n = 12), continuing through day 5 post-TBI, and tested for cognitive impairment on days 1–5 and 18. pTau, Tau, GFAP, and serum cytokines were measured at multiple time points. Animals were observed daily for cognition and motor coordination via novel object recognition. Brain sections were stained and evaluated for neuronal injury.ResultsAdministration of Ang-(1-7) daily for 5 days post-mTBI significantly increased cognitive function as compared to saline control-treated animals. Cortical and hippocampal structures showed less damage in the presence of Ang-(1-7), while Ang-(1-7) administration significantly changed the expression of pTau and GFAP in cortical and hippocampal regions as compared to control.DiscussionThese are among the first studies to demonstrate that sustained administration of Ang-(1-7) following a closed-skull, single impact mTBI significantly improves neurologic outcomes, potentially offering a novel therapeutic modality for the prevention of long-term CNS impairment following such injuries.https://www.frontiersin.org/articles/10.3389/fnbeh.2022.903980/fulltraumatic brain injuryangiotensin 1-7Mas receptorcognitive impairmentpTau |
| spellingShingle | Ryan P. Bruhns Maha Ibrahim Sulaiman Michael Gaub Esther H. Bae Rachel B. Davidson Knapp Anna R. Larson Angela Smith Deziree L. Coleman William D. Staatz Alexander J. Sandweiss Bellal Joseph Meredith Hay Tally M. Largent-Milnes Todd W. Vanderah Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury Frontiers in Behavioral Neuroscience traumatic brain injury angiotensin 1-7 Mas receptor cognitive impairment pTau |
| title | Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury |
| title_full | Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury |
| title_fullStr | Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury |
| title_full_unstemmed | Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury |
| title_short | Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury |
| title_sort | angiotensin 1 7 improves cognitive function and reduces inflammation in mice following mild traumatic brain injury |
| topic | traumatic brain injury angiotensin 1-7 Mas receptor cognitive impairment pTau |
| url | https://www.frontiersin.org/articles/10.3389/fnbeh.2022.903980/full |
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