Abstract
BackgroundA major consequence of stroke is permanent motor disturbance, such as postural imbalance and loss of skilled movement. The degree of neuronal and functional loss and subsequent recovery after stroke is influenced by hypothalamic-pituitary-adrenal axis activation and the response to glucocorticoid hormones. This study investigated if recovery after stroke is related to glucocorticoid receptor (GR) activation in a rat model of stroke.MethodsAdult male rats were pre-trained and tested in a skilled reaching task and received a focal ischemic motor cortex lesion. One group of animals received daily restraint stress starting one week pre-lesion up to three weeks post-lesion. Immuno-histochemical analysis of GR expression was performed to determine receptor activation.ResultsStress reduced reaching success in naïve animals and diminished recovery of limb use. Exaggerated functional loss in stressed rats was related to increased GR activation in the lesion hemisphere as indicated by nuclear GR location.ConclusionThese findings provide a mechanistic link between stress-induced motor disability and GR activation in a rat model of stroke. The elevated receptor activation proposes synergistic effects of stress and stroke to modulate the impact of glucocorticoids on motor system function at the genomic level. The modulation of GR biosynthesis may alter responsiveness to stroke treatment and compromise recovery.
Highlights
Common symptoms of stroke include motor disturbances, such as postural imbalance and disturbed skilled movement [1,2,3]
This study describes the effects of psychological stress on glucocorticoid receptor (GR) expression and activation, and its impact on recovery and outcome after ischemic lesion in a rat model
The Stress group showed a decrease on days 2, 3, 4 and 5 pre-lesion when compared to Controls [day 2: t(21) = -4.36, p < 0.001; day 3: t(21) = -3.48, p < 0.01; day 4: t(21) = -2.52, p < 0.05; day 5: t(21) = -3.02, p < 0.01; (Figure 1C)]
Summary
Common symptoms of stroke include motor disturbances, such as postural imbalance and disturbed skilled movement [1,2,3]. The degree of spontaneous functional recovery after stroke is determined by inflammatory processes, which are modulated by stress and activity of the hypothalamic-pituitary-adrenal (HPA) axis [4]. Stress and high levels of glucocorticoids (GCs) are associated with poor stroke outcome and high morbidity [5,6,7,8]. A major consequence of stroke is permanent motor disturbance, such as postural imbalance and loss of skilled movement. The degree of neuronal and functional loss and subsequent recovery after stroke is influenced by hypothalamic-pituitary-adrenal axis activation and the response to glucocorticoid hormones. This study investigated if recovery after stroke is related to glucocorticoid receptor (GR) activation in a rat model of stroke
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