Differential effects of glucocorticoid and mineralocorticoid antagonism on anxiety behavior in mild traumatic brain injury

Abstract

Mild traumatic brain injuries (TBIs) comprise three-quarters of all TBIs occurring in the United States annually, and psychological symptoms arising from them can last years after injury. One commonly observed symptom following mild TBI is generalized anxiety. Most mild TBIs happen in stressful situations (sports, war, domestic violence, etc.) when glucocorticoids are elevated in the brain at the time of impact, and glucocorticoids have negative effects on neuronal health following TBI. Therefore, blocking glucocorticoid receptors might prevent emergence of anxiety symptoms post-injury. Adult male rats received mifepristone (20mg/kg) or spironolactone (50mg/kg) to block glucocorticoid and mineralocorticoid receptors, respectively, 40min prior to being exposed to acute social defeat stress followed immediately by mild TBI. In defeated rats with concomitant mild TBI, mifepristone restored time spent in the open arms of an elevated plus maze to control levels, demonstrating for the first time that glucocorticoid receptors play a critical role in the development of anxiety after mild TBI. Future treatments could target these receptors, alleviating anxiety as a major side effect in victims of mild TBI sustained in stressful situations.

The glucocorticoid antagonist mifepristone attenuates sound‐induced long‐term deficits in auditory nerve response and central auditory processing in female rats

“…Rats received a single i.p. injection of either vehicle (polyethylene glycol and ethanol; 1:10, 2 ml/kg), the MR antagonist spironolactone (75 mg/kg), or the GR antagonist mifepristone (100 mg/kg) (28, 29) 90 min before sham or noise exposure. As shown in Fig.…”

Higher Anxiety Symptoms Predict Progressive Hippocampal Atrophy in the Chronic Stages of Moderate to Severe Traumatic Brain Injury

“…The relationship between anxiety and atrophy (particularly of the right HPC head) suggests the involvement of glucocorticoids. Glucocorticoids have been shown to induce both negative HPC remodeling 46,47 as well as anxiety-related behavior 48,49 ; thus, the mechanism for the relationship between anxiety symptoms and right HPC volume loss deserves further inquiry. It may be worth noting that anxiety has been associated with prolonged activity of the HPA axis.…”

A retrospective analysis of postoperative hypokalemia in pituitary adenomas after transsphenoidal surgery

“…We hypothesized intraoperative low potassium content was the cause of postoperative hypokalemia. First, it is well known that glucocorticoid and mineralocorticoid release intraoperatively usually counters the fall in serum potassium (Chauhan et al, 2015; Fox et al, 2016; Frindt & Palmer, 2012; Lang & Vallon, 2012; Ohtake et al, 2014; Salyer et al, 2013; Terker & Ellison, 2015). Moreover, patients with ACTH-pituitary adenomas are predisposed to high glucocorticoid levels, which can cause hypokalemia (Bondugulapati et al, 2016; Carrasco & Villanueva, 2014; Cassarino et al, 2017).…”