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Updated: Jan 3, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Inadequate Expression and Activation of Mineralocorticoid Receptor Aggravates Spatial Memory Impairment after
Bin Zhang1, Xueli Zhu2, Liang Wang3
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Abstract:
The administration of glucocorticoids (GCs) for the treatment of traumatic brain injury (TBI) is controversial. Both protective and deleterious effects of GCs on the brain have been reported in previous studies, while the mechanisms are unclear. Most experimental studies have reported glucocorticoid receptor (GR)-mediated deleterious effects after TBI. Sufficient mineralocorticoid receptor (MR) activation was reported to be indispensable for normal function and survival of hippocampal neurons, but changes in MR expression and activation and the roles of MRs in the survival of neurons after TBI remain unclear. We hypothesized that inadequate MR expression and activation caused by TBI aggravates posttraumatic hippocampal apoptosis but that restoration by restoring MRs promotes the survival of neurons. Using a rat controlled cortical impact model, we examined plasma corticosterone, MR expression and activation, neuronal apoptosis in the hippocampus, and spatial memory on day 3 after injury with and without fludrocortisone (1 mg/kg) treatment. Plasma corticosterone levels were significantly reduced after TBI. In addition, both MR expression and activation were inhibited. Fludrocortisone treatment significantly increased both the expression and activation of MRs, reduced the number of apoptotic neurons and cell loss in the ipsilateral hippocampus, and subsequently improved spatial memory. Its protective effects were counteracted by the MR antagonist spironolactone. The results suggest that adequate expression and activation of MRs is crucial for the survival of neurons after TBI and that fludrocortisone protects hippocampal neurons via promoting MR expression and activation.
Insights
Traumatic brain injury (TBI) disrupts mineralocorticoid receptor (MR) function, increasing neuron death. Restoring MR activation with fludrocortisone protects hippocampal neurons and improves memory after TBI.
Area of Science:
- Neuroscience
- Endocrinology
- Traumatology
Background:
- Glucocorticoids (GCs) have controversial effects on traumatic brain injury (TBI) outcomes.
- While glucocorticoid receptor (GR) activation is often linked to negative effects post-TBI, the role of mineralocorticoid receptors (MRs) remains unclear.
- MR activation is essential for hippocampal neuron survival, but its response to TBI is not well understood.
Purpose of the Study:
- To investigate the role of MRs in hippocampal neuron survival following TBI.
- To determine if restoring MR activation can mitigate TBI-induced neuronal damage and cognitive deficits.
Main Methods:
- A controlled cortical impact (CCI) rat model was used to induce TBI.
- Evaluated plasma corticosterone, MR expression and activation, hippocampal apoptosis, and spatial memory.
- Assessed the effects of fludrocortisone (MR agonist) and spironolactone (MR antagonist) treatment.
Main Results:
- TBI significantly reduced plasma corticosterone, MR expression, and MR activation.
- Fludrocortisone treatment increased MR expression and activation, reduced hippocampal apoptosis and neuronal loss, and improved spatial memory.
- The protective effects of fludrocortisone were reversed by the MR antagonist spironolactone.
Conclusions:
- Adequate MR expression and activation are critical for hippocampal neuron survival after TBI.
- Fludrocortisone exerts neuroprotective effects in TBI by enhancing MR expression and activation.
- Targeting MRs represents a potential therapeutic strategy for managing TBI.
