Author Response: Role Of Sleep-Disordered Breathing And Sleep-Wake Disturbances For Stroke And Stroke Recovery.

Abstract

Drs. Fuchs and Strasser raise the question of how the increased stroke incidence and disturbed stroke recovery that are observed both in patients with sleep-disordered breathing and sleep-wake disturbances are mediated. Increased stroke incidence may be due to excessive sympathetic activation that results in arterial hypertension, inflammation, and atherosclerosis.1 Conversely, disturbed stroke recovery and neuroplasticity might indeed result from disturbed tryptophan metabolism, as proposed by Drs. Fuchs and Strasser. Reduced formation of serotonin from tryptophan is well-known from inflammation-associated depression, where serotonin decreased due to excessive synthesis of the tryptophan metabolite kynurenine.2 Analogies to depression are compelling, since depression is frequent both in disturbed sleep and stroke recovery. Alternative mechanisms of impaired stroke recovery and neuroplasticity are direct effects of inflammatory cytokines, hypothalamo-pituitary abnormalities (i.e., melanin-concentrating hormone, orexin/hypocretin, adrenocorticotropic hormone, or cortisol elevations), and glutamatergic NMDA overactivation induced by quinolinic acid, a kynurenine metabolite.2,3 In rat models, melanin-concentrating hormone and orexin/hypocretin are excessively induced following sleep deprivation that disturbs stroke recovery and brain plasticity.3,4 In mice, stroke recovery and neuroplasticity can be amplified by sodium oxybate, which promotes slow-wave sleep.5 Further in-depth scrutiny of factors mediating disturbed stroke recovery and poor stroke outcome might reveal new targets for therapy.