Interactions between remote ischemic conditioning and post-stroke sleep regulation / 医学前沿

Sleep disturbances are common in patients with stroke, and sleep quality has a critical role in the onset and outcome of stroke. Poor sleep exacerbates neurological injury, impedes nerve regeneration, and elicits serious complications. Thus, exploring a therapy suitable for patients with stroke and sleep disturbances is imperative. As a multi-targeted nonpharmacological intervention, remote ischemic conditioning can reduce the ischemic size of the brain, improve the functional outcome of stroke, and increase sleep duration. Preclinical/clinical evidence showed that this method can inhibit the inflammatory response, mediate the signal transductions of adenosine, activate the efferents of the vagal nerve, and reset the circadian clocks, all of which are involved in sleep regulation. In particular, cytokines tumor necrosis factor α (TNFα) and adenosine are sleep factors, and electrical vagal nerve stimulation can improve insomnia. On the basis of the common mechanisms of remote ischemic conditioning and sleep regulation, a causal relationship was proposed between remote ischemic conditioning and post-stroke sleep quality.

Effect of Gastrodia elata on improving sleep in mice and its mechanism / 中草药

Objective: To investigate the sleep promoting effect of Gastrodia elata on mice and its effect on the central dopamine (DA) system, and study the mechanisms of gastrodin, the active constituent of G. elata. Methods: Five groups of mice were treated by gavage with saline, gastrodia, olive oil, gastrodia mixed with olive oil and positive control Estazolam, respectively, for 20 d (10 mice per group). Hypnosis induced by suprathreshold and subthreshold doses of Pentobarbital sodium were used to evaluate the effect of G. elata on sleep in mice. Sleep latency, occurrence rate and duration were recorded at the 7th and 20th day. The DA content in the brain tested by ELISA and the expression of DA receptor subtypes detected by qRT-PCR were used to determine the effect of G. elata on central DA system. Western blotting was further used to detect the expression levels of ERK pathway related protein. Results: After 20 d of gavage, the sleep latency of mice was significantly shortened, the sleep occurrence rate was increased, the sleep duration was prolonged, and the content of brain DA was significantly increased. At the same time, the expression levels of all the dopamine receptor subtypes were significantly up-regulated. Furthermore, the gastrodin, the active constituent of G. elata, could activate the dopamine receptor D2 rather than the D1-mediated signaling pathway. Conclusion: G. elata might regulate sleep by up-regulating the activity of central DA system. Gastrodin, the active constituent of G. elata, could play a regulating role through D2-mediated signaling pathway.

Stress, Sleep Physiology, and Related Insomnia Disorders

Excessive stress gives rise to disturbances in various systems in humans and activates defense mechanisms to maintain homeostasis in the body. Sleep is an essential biological process of which the underlying regulating mechanism involves numerous anatomical structures and biochemical substances that can be compromised by stress and the immune system. Immune sub-stances such as interleukin-1beta and tumor necrosis factor are related to the homeostatic process of sleep. Interleukin-1beta interacts by being involved in an immune regulating feedback chain that activates the hypothalamo-pituitary-adrenal axis which, in turn, is related to the circadian process. Moreover, stress-induced insomnia activates the hypothalamo-pituitary-adrenal axis further to bring about a vicious cycle of stress and insomnia. The pathophysiological theory responsible for chronic insomnia is that of stressdiathesis, which is a series of processes consisting of predisposition, precipitating, and perpetuating factors. In clinical practice, as the process in which stressinduced insomnia passes into a chronic course is directly related to treatment, the understanding of perpetuating factors is indispensable. Sleep disturbance is a very common complaint among pa-tients with posttraumatic stress disorder. Increased noradrenergic activity and REM sleep dysregul-ation seem to have a role in mediating sleep disturbances of this disorder. Sleep disturbance must always be taken into account as an important clinical variable whenever evaluating or managing stress.