A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system.

Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events. Through a quasi-randomized controlled study, we show that a single high dexamethasone dose significantly reduces in a dose-dependent manner the levels of GluA1-Ser831 phosphorylation in the amygdala resected during surgery for temporal lobe epilepsy. This is the first report demonstrating GC effects on key markers of synaptic neuroplasticity in the human limbic system. The results contribute to understanding how GC affects the human brain under physiologic and pharmacologic conditions.

Side of pupillary mydriasis predicts the cognitive prognosis in patients with severe traumatic brain injury.

BACKGROUND: Pupils' abnormalities are associated to bad prognosis in traumatic brain injury. We investigated the association between the side of pupil mydriasis and the long-term cognitive performance of patients with severe traumatic brain injury (TBI). METHODS: We analyzed the cognitive performance of patients admitted at the intensive care unit with isochoric pupils (IP, n = 28), left mydriasis (LM, n = 10), right mydriasis (RM, n = 9) evaluated in mean 2.5 years after the severe TBI and controls (n = 26) matched for age, sex and education level. RESULTS: Patients and controls had similar scores in the four WAIS-III investigated subtests. In comparison with controls, LM patients had lower scores in Letters and Category Fluency and IP patients in Category Fluency. Among the 10 evaluated memory tests, LM patients had lower scores than controls in eight, RM patients in two and IP in three memory tests. IP and RM were 3.5 to nine times more associated to significant impairment (cognitive scores under the percentile 10 of controls) in six of 16 investigated cognitive tests. LM was six to 15 times more associated to significant impairment in 10 of 16 cognitive tests. The association among the pupil abnormalities and cognitive performances remained significant after the multiple linear regression analysis controlling for age, gender, admission coma Glasgow scale and serum glucose, presence of associated trauma, and cranial computed tomography abnormalities. CONCLUSION: Side of admission pupil abnormalities may be a useful variable to improve prognostic models for long-term cognitive performance in severe TBI patients.