The capsaicin receptor TRPV1 reduces sepsis-associated brain injury in mice by inhibiting pyroptosis
Abstract Purpose Sepsis is a life-threatening disorder marked by organ dysfunction due to infection. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective, ligand-gated cation channel activated by multiple stimuli. This study investigates the role of TRPV1 in sepsis-associated encephal...
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Springer
2025-07-01
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| Series: | Anesthesiology and Perioperative Science |
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| Online Access: | https://doi.org/10.1007/s44254-025-00115-4 |
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| author | Menghong Long Zhenyu Hu Feiyu Long Yingxu Chen Li Liu Maohua Wang |
| author_facet | Menghong Long Zhenyu Hu Feiyu Long Yingxu Chen Li Liu Maohua Wang |
| author_sort | Menghong Long |
| collection | DOAJ |
| description | Abstract Purpose Sepsis is a life-threatening disorder marked by organ dysfunction due to infection. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective, ligand-gated cation channel activated by multiple stimuli. This study investigates the role of TRPV1 in sepsis-associated encephalopathy (SAE). Methods The SAE models of wild-type and TRPV1 knockout (TRPV1-/-) mice were established through intraperitoneal injection of 10 mg/kg lipopolysaccharide. Brain tissues and serum were collected 24 h post-injection for analysis. Rectal temperature was monitored at 12 and 24 h, and the 7-day survival rate was recorded. Mice were pretreated with capsaicin (CAP), and brain tissue and serum were collected for detection. Results TRPV1 expression was significantly elevated in the brain tissues of mice with sepsis. TRPV1-/- aggravated SAE symptoms, as evidenced by a significant decrease in rectal temperature, a reduced 7-day survival rate, an elevated Murine Sepsis Score, and greater impairment in learning and memory. Mechanistically, TRPV1 deficiency increased NF-κB, pyroptosis-related proteins, and levels of IL-6 and TNF-α in SAE mice. CAP pretreatment significantly reduced abnormal neurons in the CA1 region, decreased NF-κB, Pro-caspase1, and Cleaved-caspase1 in brain tissues, and lowered IL-1β and IL-18 serum levels, with this effect being TRPV1-dependent. Conclusion In summary, TRPV1 deficiency worsens SAE-induced damage in mice, associated with activation of NF-κB and pyroptosis pathways. CAP pretreatment improved the damage caused by SAE by activating TRPV1. |
| format | Article |
| id | doaj-art-a4d2101cfbd84d288c360b2d6be03e36 |
| institution | Kabale University |
| issn | 2731-8389 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Anesthesiology and Perioperative Science |
| spelling | doaj-art-a4d2101cfbd84d288c360b2d6be03e362025-08-20T04:01:47ZengSpringerAnesthesiology and Perioperative Science2731-83892025-07-013311310.1007/s44254-025-00115-4The capsaicin receptor TRPV1 reduces sepsis-associated brain injury in mice by inhibiting pyroptosisMenghong Long0Zhenyu Hu1Feiyu Long2Yingxu Chen3Li Liu4Maohua Wang5Department of Anesthesiology, The Affiliated Hospital, Southwest Medical UniversityDepartment of Anesthesiology, Sichuan Orthopedic HospitalDepartment of Anesthesiology, West China Hospital, Sichuan UniversityDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical UniversityDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical UniversityDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical UniversityAbstract Purpose Sepsis is a life-threatening disorder marked by organ dysfunction due to infection. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective, ligand-gated cation channel activated by multiple stimuli. This study investigates the role of TRPV1 in sepsis-associated encephalopathy (SAE). Methods The SAE models of wild-type and TRPV1 knockout (TRPV1-/-) mice were established through intraperitoneal injection of 10 mg/kg lipopolysaccharide. Brain tissues and serum were collected 24 h post-injection for analysis. Rectal temperature was monitored at 12 and 24 h, and the 7-day survival rate was recorded. Mice were pretreated with capsaicin (CAP), and brain tissue and serum were collected for detection. Results TRPV1 expression was significantly elevated in the brain tissues of mice with sepsis. TRPV1-/- aggravated SAE symptoms, as evidenced by a significant decrease in rectal temperature, a reduced 7-day survival rate, an elevated Murine Sepsis Score, and greater impairment in learning and memory. Mechanistically, TRPV1 deficiency increased NF-κB, pyroptosis-related proteins, and levels of IL-6 and TNF-α in SAE mice. CAP pretreatment significantly reduced abnormal neurons in the CA1 region, decreased NF-κB, Pro-caspase1, and Cleaved-caspase1 in brain tissues, and lowered IL-1β and IL-18 serum levels, with this effect being TRPV1-dependent. Conclusion In summary, TRPV1 deficiency worsens SAE-induced damage in mice, associated with activation of NF-κB and pyroptosis pathways. CAP pretreatment improved the damage caused by SAE by activating TRPV1.https://doi.org/10.1007/s44254-025-00115-4TRPV1Septic encephalopathyNF-κBPyroptosisCapsaicinNeuroprotection |
| spellingShingle | Menghong Long Zhenyu Hu Feiyu Long Yingxu Chen Li Liu Maohua Wang The capsaicin receptor TRPV1 reduces sepsis-associated brain injury in mice by inhibiting pyroptosis Anesthesiology and Perioperative Science TRPV1 Septic encephalopathy NF-κB Pyroptosis Capsaicin Neuroprotection |
| title | The capsaicin receptor TRPV1 reduces sepsis-associated brain injury in mice by inhibiting pyroptosis |
| title_full | The capsaicin receptor TRPV1 reduces sepsis-associated brain injury in mice by inhibiting pyroptosis |
| title_fullStr | The capsaicin receptor TRPV1 reduces sepsis-associated brain injury in mice by inhibiting pyroptosis |
| title_full_unstemmed | The capsaicin receptor TRPV1 reduces sepsis-associated brain injury in mice by inhibiting pyroptosis |
| title_short | The capsaicin receptor TRPV1 reduces sepsis-associated brain injury in mice by inhibiting pyroptosis |
| title_sort | capsaicin receptor trpv1 reduces sepsis associated brain injury in mice by inhibiting pyroptosis |
| topic | TRPV1 Septic encephalopathy NF-κB Pyroptosis Capsaicin Neuroprotection |
| url | https://doi.org/10.1007/s44254-025-00115-4 |
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