Central nervous system diseases are among the most disabling in the world. Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation as pharmacology treatments are often insufficiently effective. Conditioning the central nervous system has been proposed as a potential non-pharmacological neuro-therapeutic. Conditioning refers to a procedure by which a potentially deleterious stimulus is applied near to but below the threshold of damage to the organism to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic conditioning has been investigated in several cellular and preclinical models and is now recognized as inducing endogenous mechanisms of neuroprotection. Ischemic, traumatic, or chronic neurodegenerative diseases can benefit from hypoxic conditioning strategies aiming at preventing the deleterious consequences or reducing the severity of the pathological condition (preconditioning) or aiming at inducing neuroplasticity and recovery (postconditioning) following central nervous system injury. Hypoxic conditioning can consist in single (sustained) or cyclical (intermittent, interspersed by short period of normoxia) hypoxia stimuli which duration range from few minutes to several hours and that can be repeated over several days or weeks. This mini-review addresses the existing evidence regarding the use of hypoxic conditioning as a potential innovating neuro-therapeutic modality to induce neuroprotection, neuroplasticity and brain recovery. This mini-review also emphasizes issues which remain to be clarified and future researches to be performed in the field.Impact statement: Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation. Hypoxic conditioning may represent a harmless and efficient non-pharmacological new therapeutic modality in the field of neuroprotection and neuroplasticity, as supported by many preclinical data. Animal studies provide clear evidence for neuroprotection and neuroplasticity induced by hypoxic conditioning in several models of neurological disorders. These studies show improved functional outcomes when hypoxic conditioning is applied and provides important information to translate this intervention to clinical practice. Some studies in humans provide encouraging data regarding the tolerance and therapeutic effects of hypoxic conditioning strategies. The main issues to address in future research include the definition of the appropriate hypoxic dose and pattern of exposure, the determination of relevant physiological biomarkers to assess the effects of the treatment and the evaluation of combined strategies involving hypoxic conditioning and other pharmacological or non-pharmacological treatments.

Objective To identify candidate biomarkers of walking recovery with motor tract integrity measurements using fractional anisotropy (FA) from the corticospinal tract (CST) and alternative motor pathways in patients with moderate to severe subacute stroke. Methods Walking recovery was first assessed with generalized linear mixed model (GLMM) with repeated measures of walking scores (WS) over 2 years of follow-up in a longitudinal study of 29 patients with subacute ischemic stroke. Baseline FA measures from the ipsilesional and contralesional CST (i-CST and c-CST), cortico-reticulospinal pathway (i-CRP and c-CRP), and cerebellar peduncles were derived from a 60-direction diffusion MRI sequence on a 3T scanner. We performed correlation tests between WS and FA measures. Third, we investigated using GLMM whether motor tract integrity contributes to predict walking recovery. Results We observed significant improvements of WS over time with a plateau reached at ≈6 months after stroke. WS significantly correlated with FA measures from i-CST, c-CST, i-CRP, and bilateral cerebellar peduncles. Walking recovery was predicted by FA measures from 3 tracts: i-CST, i-CRP, and contralesional superior cerebellar peduncle (c-SCP). Diffusion tensor imaging (DTI) predictors captured 80.5% of the unexplained variance of the model without DTI. Conclusions We identified i-CST and alternative motor-related tracts (namely i-CRP and c-SCP) as candidate biomarkers of walking recovery. The role of the SCP in walk recovery may rely on cerebellar nuclei projections to the thalamus, red nucleus, and reticular formation. Our findings suggest that a set of white matter tracts, part of subcortical motor networks, contribute to walking recovery in patients with moderate to severe stroke.

Exposure to chronic hypobaric hypoxia imposes a significant physiological burden to more than 80 million humans living above 2500 m throughout the world. Among them, 50 000 live in the world's highest city, La Rinconada, located at 5000–5300 m in southern Peru. Expedition 5300 is the first scientific and medical programme led in La Rinconada to investigate the physiological adaptations and altitude‐related health issues in this unique population. Dwellers from La Rinconada have very high haemoglobin concentration (20.3 ± 2.4 g/dL; n = 57) and those with chronic mountain sickness (CMS) exhibit even higher concentrations (23.1 ± 1.7 g/dL; n = 150). These values are associated with large total haemoglobin mass and blood volume, without an associated iron deficit. These changes in intravascular volumes lead to a substantial increase in blood viscosity, which is even larger in CMS patients. Despite these large haematological changes, 24 h blood pressure monitoring is essentially normal in La Rinconada, but some results suggest impaired vascular reactivity. Echocardiography revealed large right heart dilatation and high pulmonary arterial pressure as well as left ventricle concentric remodelling and grade I diastolic dysfunction. These changes in heart dimension and function tend to be more severe in highlanders with CMS. Polygraphy evaluations revealed a large reduction in nocturnal pulse oxygen saturation (median SpO₂ = 79%), which is even more severe in CMS patients who also tended to show a higher oxygen desaturation index. The population of La Rinconada offers a unique opportunity to investigate the human responses to chronic severe hypoxia, at an altitude that is probably close to the maximum altitude human beings can permanently tolerate without presenting major health issues. image

Recent scientific findings in the field of sleep disordered breathing have characterised a variety of phenotypes in obstructive sleep apnoea. These findings have prompted investigations aiming to achieve a more precise differentiation and description of the entities of central sleep apnoea (CSA). There is increasing evidence for the heterogeneity of CSA in terms of underlying aetiology, pathophysiological concepts, treatment response and outcome. Assigning patients to these phenotypes allows for the selection of individualised therapies. Major pathophysiological characteristics include loop gain, apnoeic threshold, breathing regulation and neuromuscular mechanics. Chronic heart failure is the most important underlying disease, leading to nonhypercapnic CSA based on increased loop and controller gain. Although many questions remain, this review tries to describe the current knowledge on the pathophysiology of the clinical entities. The description of prognostic aspects may guide treatment indication and the selection of pharmacotherapy and invasive options. In addition, the paper provides an update on the current understanding of adaptive servo-ventilation and its role in the treatment of CSA.