Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive narrowing or collapse of the pharyngeal airway during sleep. The disorder is associated with major comorbidities including excessive daytime sleepiness and increased risk of cardiovascular disease. The underlying pathophysiology is multifactorial and may vary considerably between individuals. Important risk factors include obesity, male sex, and aging. However, the physiological mechanisms underlying these risk factors are not clearly understood. This brief review summarizes the current understanding of OSA pathophysiology in adults and highlights the potential mechanisms underlying the principal risk factors. In addition, some of the pathophysiological characteristics associated with OSA that may modulate disease severity are illustrated. Finally, the potential for novel treatment strategies, based on an improved understanding of the underlying pathophysiology, is also discussed with the ultimate aim of stimulating research ideas in areas where knowledge is lacking.

https://www.atsjournals.org/doi/pdf/10.1513/pats.200707-114MG

Pathophysiology of Adult Obstructive Sleep Apnea

Turning blood into brain: Cells bearing neuronal antigens generated in vivo from bone marrow

A common but significant change associated with aging is a profound disruption to the daily sleep-wake cycle. It has been estimated that as many as 50% of older adults complain about difficulty initiating or maintaining sleep. Poor sleep results in increased risk of significant morbidity and mortality. Moreover, in younger adults, compromised sleep has been shown to have a consistent effect on cognitive function, which may suggest that sleep problems contribute to the cognitive changes that accompany older age. The multifactorial nature of variables affecting sleep in old age cannot be overstated. Changes in sleep have been thought to reflect normal developmental processes, which can be further compromised by sleep disturbances secondary to medical or psychiatric diseases (e.g., chronic pain, dementia, depression), a primary sleep disorder that can itself be age-related (e.g., Sleep Disordered Breathing and Periodic Limb Movements During Sleep), or some combination of any of these factors. Given that changes in sleep quality and quantity in later life have implications for quality of life and level of functioning, it is imperative to distinguish the normal age-related sleep changes from those originating from pathological processes.

Sleep and sleep disorders in older adults.

Mesenchymal stem cells (MSCs) are emerging as a promising therapeutic approach of cell-based therapy for a wide range of autoimmune disorders and degenerative diseases. In preclinical and clinical studies, MSCs have been shown to be highly efficient in treating graft-versus-host disease, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, myocardial infarction, liver cirrhosis, inflammatory bowel disease, and other disorders. The underlying therapeutic mechanisms of MSCs include their homing efficiency to the tissue injury sites, their differentiation potential, their capability to produce a large amount of trophic factors, and their immunomodulatory effect. Because tissue damage sites are complicated milieus with distinct types of inflammatory cells and factors, available data have demonstrated that the properties of MSCs could be fundamentally influenced by the inflammatory elements. Thus, an understanding of the interaction between MSCs and the inflammatory microenvironment will provide critical information in revealing the precise in vivo mechanisms of MSC-mediated therapeutic effects and designing more practical protocols for clinical use of these cells.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.5966/sctm.2011-0019

Concise Review: Mesenchymal Stem Cells and Translational Medicine: Emerging Issues

Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction with high disability and mortality. In recent years, mesenchymal stem cell (MSC)-secreted nano-sized exosomes have shown great potential for promoting functional behavioral recovery following SCI. However, MSCs are usually exposed to normoxia in vitro, which differs greatly from the hypoxic micro-environment in vivo. Thus, the main purpose of this study was to determine whether exosomes derived from MSCs under hypoxia (HExos) exhibit greater effects on functional behavioral recovery than those under normoxia (Exos) following SCI in mice and to seek the underlying mechanism. Electron microscope, nanoparticle tracking analysis (NTA), and western blot were applied to characterize differences between Exos and HExos group. A SCI model in vivo and a series of in vitro experiments were performed to compare the therapeutic effects between the two groups. Next, a miRNA microarray analysis was performed and a series of rescue experiments were conducted to verify the role of hypoxic exosomal miRNA in SCI. Western blot, luciferase activity, and RNA-ChIP were used to investigate the underlying mechanisms. Our results indicate that HExos promote functional behavioral recovery by shifting microglial polarization from M1 to M2 phenotype in vivo and in vitro. A miRNA array showed miR-216a-5p to be the most enriched in HExos and potentially involved in HExos-mediated microglial polarization. TLR4 was identified as the target downstream gene of miR-216a-5p and the miR-216a-5p/TLR4 axis was confirmed by a series of gain- and loss-of-function experiments. Finally, we found that TLR4/NF-κB/PI3K/AKT signaling cascades may be involved in the modulation of microglial polarization by hypoxic exosomal miR-216a-5p. Hypoxia preconditioning represents a promising and effective approach to optimize the therapeutic actions of MSC-derived exosomes and a combination of MSC-derived exosomes and miRNAs may present a minimally invasive method for treating SCI.

/pdf/exosome-shuttled-mir-216a-5p-from-hypoxic-preconditioned-588e840pp3.pdf

Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization.

Background: Autologous bone marrow mesenchymal cells that include stem cells (MSCs) are a clinically attractive cellular therapy option to try to treat severe spinal cord injury (SCI). Objective: T...

https://journals.sagepub.com/doi/pdf/10.1177/1545968310369801

Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury.

Sleep and respiratory stimulus specific dampening of cortical responsiveness in OSAS

Sleep evoked delta frequency responses show a linear decline in amplitude across the adult lifespan.

The motor cortex (MC) receives an excitatory input from the cerebellum which is reduced in patients with cerebellar lesions. High-frequency repetitive transcranial magnetic stimulation (rTMS) induces cortical facilitation which can counteract the reduced cerebellar drive to the MC. Our study included 24 relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients with dysmetria. The patients were divided into two groups: Group A received two sessions of real MC rTMS and Group B received one session of real rTMS and one session of sham rTMS. Ten healthy volunteers formed group C. Evaluation was carried out using the nine-hole pegboard task and the cerebellar functional system score (FSS) of the expanded disability status scale (EDSS). Group A patients showed a significant improvement in the time required to finish the pegboard task (P = 0.002) and in their cerebellar FSS (P = 0.000) directly after the second session and 1 month later. The RRMS patients showed more improvement than the SPMS patients. Group B patients did not show any improvement in the pegboard task or the cerebellar FSS. These results indicate that MC rTMS can be a promising option in treating both RRMS or SPMS patients with cerebellar impairment and that its effect can be long-lasting.

Motor cortex rTMS improves dexterity in relapsing-remitting and secondary progressive multiple sclerosis.

Background Autism spectrum disorder is a neurodevelopmental disorder that is characterized mainly by difficulties in social interaction and communication. Studies have suggested abnormal neural connectivity patterns in the brains of patients with autism. Objective The current work aimed to study the quantitative electroencephalography (EEG) findings in autistic children and compare it with those of normal controls. Methods The EEG recordings of 21 autistic children between 4 and 12 years of age were compared with those of 21 age-matched and sex-matched controls under an eyes-opened condition. Differences in cerebral functioning were examined using measurements of absolute and relative power and intrahemispheric and interhemispheric coherence. Results There were statistically significant differences in EEG power between the autistic and control groups, with greater absolute of delta and theta power especially at the frontal region in autistic children. There was also global reduction in relative alpha and beta power especially in the frontal, central, and posterior regions in autistic children. In addition, there was a pattern of underconnectivity and overconnectivity when measuring the intrahemispheric and interhemispheric coherence in the autistic compared with the control group. Conclusion These results suggested regional dysfunction of the brain in autistic children, along with a pattern of abnormal neural connectivity, which could explain the autistic symptomatology.

Lamia Afifi

Papers

Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury.

Sleep and respiratory stimulus specific dampening of cortical responsiveness in OSAS

Sleep evoked delta frequency responses show a linear decline in amplitude across the adult lifespan.

Motor cortex rTMS improves dexterity in relapsing-remitting and secondary progressive multiple sclerosis.

Quantitative EEG in autistic children