ArticleJournal of neuroinflammation2020
Corticosteroid receptor rebalancing alleviates critical illness-related corticosteroid insufficiency after traumatic brain injury by promoting paraventricular nuclear cell survival via Akt/CREB/BDNF signaling.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07180277 (A Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Methylprednisolone Sodium Succinate Injection in Patients With Moderate to Severe Traumatic Brain Injury), which is not on this map. Cited by 13 papers.
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A Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Methylprednisolone Sodium Succinate Injection in Patients With Moderate to Severe Traumatic Brain Injury
Who cites it
13 citing papers in PubMed.
- Article
- Injectable nanocomposite hydrogel for localized precision delivery of dexamethasone after traumatic brain injury: dual modulation of neuroinflammation and blood-brain barrier restoration.Journal of translational medicine · 2025Article
- Balancing Anti-Inflammation and Neurorepair: The Role of Mineralocorticoid Receptor in Regulating Microglial Phenotype Switching After Traumatic Brain Injury.CNS neuroscience & therapeutics · 2025Article
- Inhibition of sympathetic tone via hypothalamic descending pathway propagates glucocorticoid-induced endothelial impairment and osteonecrosis of the femoral head.Bone research · 2024Article
- Neurotrophins and neural stem cells in posttraumatic brain injury repair.Animal models and experimental medicine · 2024Review
- Recent advances in the crosstalk between the brain-derived neurotrophic factor and glucocorticoids.Frontiers in endocrinology · 2024Review
- Review
- Chronic Corticosterone Exposure Suppresses Copper Transport through GR-Mediated Intestinal CTR1 Pathway in Mice.Biology · 2023Article
- TREM2 activation alleviates neural damage via Akt/CREB/BDNF signalling after traumatic brain injury in mice.Journal of neuroinflammation · 2022Article
- Short-Term Cortical Electrical Stimulation during the Acute Stage of Traumatic Brain Injury Improves Functional Recovery.Biomedicines · 2022Article
- Brain Trauma, Glucocorticoids and Neuroinflammation: Dangerous Liaisons for the Hippocampus.Biomedicines · 2022Review
- The Dual Dose-Dependent Effects of Corticosterone on Hippocampal Cell Apoptosis After Traumatic Brain Injury Depend on the Activation Ratio of Mineralocorticoid Receptors to Glucocorticoid Receptors.Frontiers in pharmacology · 2021Article
- Article
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Authors and funding
7 authors.
Funding
Abstract
backgroundWe previously found that high-dose methylprednisolone increased the incidence of critical illness-related corticosteroid insufficiency (CIRCI) and mortality in rats with traumatic brain injury (TBI), whereas low-dose hydrocortisone but not methylprednisolone exerted protective effects. However, the receptor-mediated mechanism remains unclear. This study investigated the receptor-mediated mechanism of the opposite effects of different glucocorticoids on the survival of paraventricular nucleus (PVN) cells and the incidence of CIRCI after TBI.
methodsBased on controlled cortical impact (CCI) and treatments, male SD rats (n = 300) were randomly divided into the sham, CCI, CCI + GCs (methylprednisolone 1 or 30 mg/kg/day; corticosterone 1 mg/kg/day), CCI + methylprednisolone+RU486 (RU486 50 mg/kg/day), and CCI + corticosterone+spironolactone (spironolactone 50 mg/kg/day) groups. Blood samples were collected 7 days before and after CCI. Brain tissues were collected on postinjury day 7 and processed for histology and western blot analysis.
resultsWe examined the incidence of CIRCI, mortality, apoptosis in the PVN, the receptor-mediated mechanism, and downstream signaling pathways on postinjury day 7. We found that methylprednisolone and corticosterone exerted opposite effects on the survival of PVN cells and the incidence of CIRCI by activating different receptors. High-dose methylprednisolone increased the nuclear glucocorticoid receptor (GR) level and subsequently increased cell loss in the PVN and the incidence of CIRCI. In contrast, low-dose corticosterone but not methylprednisolone played a protective role by upregulating mineralocorticoid receptor (MR) activation. The possible downstream receptor signaling mechanism involved the differential effects of GR and MR on the activity of the Akt/CREB/BDNF pathway.
conclusionThe excessive activation of GR by high-dose methylprednisolone exacerbated apoptosis in the PVN and increased CIRCI. In contrast, refilling of MR by corticosterone protects PVN neurons and reduces the incidence of CIRCI by promoting GR/MR rebalancing after TBI.
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