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The nongenomic neuroprotective effects of estrogen, E2-BSA, and G1 following traumatic brain injury: PI3K/Akt and histopathological study

  • Ladan Amirkhosravi , Mohammad Khaksari EMAIL logo , Mojgan Sanjari and Parisa Khorasani
Published/Copyright: March 20, 2024
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Hormone Molecular Biology and Clinical Investigation
From the journal Hormone Molecular Biology and Clinical Investigation Volume 45 Issue 1

Abstract

Objectives

Studies suggest that both genomic and nongenomic pathways are involved in mediating the salutary effects of steroids following traumatic brain injury (TBI). This study investigated the nongenomic effects of 17β-estradiol (E2) mediated by the PI3K/p-Akt pathway after TBI.

Methods

Ovariectomized rats were apportioned to E2, E2-BSA (E2 conjugated to bovine serum albumin), G1 [G-protein-coupled estrogen receptor agonist (GPER)] or their vehicle was injected following TBI, whereas ICI (classical estrogen receptor antagonist), G15 (GPER antagonist), ICI + G15, and their vehicles were injected before the induction of TBI and injection of drugs. Diffuse TBI was induced by the Marmarou model. Evans blue (EBC, 5 h), brain water contents (BWC), histopathological changes, and brain PI3K and p-Akt protein expressions were measured 24 h after TBI. The veterinary comma scale (VCS) was assessed before and at different times after TBI.

Results

The results showed a reduction in BWC and EBC and increased VCS in the E2, E2-BSA, and G1 groups. Also, E2, E2-BSA, and G1 reduced brain edema, inflammation, and apoptosis. The ICI and G15 inhibited the beneficial effects of E2, E2-BSA, and G1 on these parameters. All drugs, following TBI, prevented the reduction of brain PI3K/p-Akt expression. The individual or combined use of ICI and G15 eliminated the beneficial effects of E2, E2-BSA, and G1 on PI3K/p-Akt expressions.

Conclusions

These findings indicated that PI3K/p-Akt pathway plays a critical role in mediating the salutary effects of estradiol on histopathological changes and neurological outcomes following TBI, suggesting that GPER and classic ERs are involved in regulating the expression of PI3K/p-Akt.

Keywords: nongenomic signaling; neuroprotection; E2-BSA; G1; PI3K/Akt; traumatic brain injury (TBI)
Corresponding author: Mohammad Khaksari, Professor, Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran, Phone: +98-34-33257581, E-mail:

  1. Research ethics: The Institutional Ethics, Animal Care and Use Committee of the Kerman University of Medical Sciences approved all animal experiment procedures (IR.KMU.REC.1396.1540).

  2. Informed consent: Not applicable.

  3. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: The authors state no conflict of interest.

  5. Research funding: None declared.

  6. Data availability: The raw data can be obtained on request from the corresponding author.

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Received: 2023-09-19
Accepted: 2024-02-28
Published Online: 2024-03-20

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Original Articles
  3. The nongenomic neuroprotective effects of estrogen, E2-BSA, and G1 following traumatic brain injury: PI3K/Akt and histopathological study
  4. Comparative study of radioprotective effects of endurance training in irradiation-induced nephropathy of rat model
  5. Association of serum NF-κB levels with peripheral neuropathy in type 2 diabetes mellitus patients: a pilot study
  6. Case Report
  7. Mature cystic ovarian teratoma with squamous cell carcinoma transformation: a case report and literature review
https://doi.org/10.1515/hmbci-2023-0066
Keywords for this article
nongenomic signaling; neuroprotection; E2-BSA; G1; PI3K/Akt; traumatic brain injury (TBI)

Articles in the same Issue

  1. Frontmatter
  2. Original Articles
  3. The nongenomic neuroprotective effects of estrogen, E2-BSA, and G1 following traumatic brain injury: PI3K/Akt and histopathological study
  4. Comparative study of radioprotective effects of endurance training in irradiation-induced nephropathy of rat model
  5. Association of serum NF-κB levels with peripheral neuropathy in type 2 diabetes mellitus patients: a pilot study
  6. Case Report
  7. Mature cystic ovarian teratoma with squamous cell carcinoma transformation: a case report and literature review
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