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In normal environments and in the absence of pathology, at least over acute time frames, hypercapnia is usually managed readily via the respiratory chemoreflex arcs and\/or acid\u2013base buffering capacity, such that there is minimal impact on cerebrovascular and neurological function. However, in non\u2010normal environments, such as enclosed spaces, or with pathology, extended exposures to elevations in  can be detrimental to cerebral health. Given the direct effect of protons on cellular function, even if pH is normalized, it is feasible that higher proton concentrations could still produce detrimental effects. Although it seems that humans can work safely in mildly hypercapnic environments for extended periods, chronic respiratory acidosis can cause bone demineralization, renal calcification, perinatal developmental abnormalities, systemic inflammation and impairments in cognitive function and visuomotor skills and can produce cerebral acidosis, potentially inducing sustained alterations in cerebral function. With the advancement of new initiatives in spaceflight, including proposed long\u2010duration missions to Mars, the study of the effects of chronic inspired CO\n                    <jats:sub>2<\/jats:sub>\n                    on human health is relevant. In this review, we draw on evidence from preclinical, physiological and clinical research in humans to summarize the cerebral ramifications of prolonged and chronic exposures to elevated partial pressures of inspired CO\n                    <jats:sub>2<\/jats:sub>\n                    and respiratory acidosis.\n                  <\/jats:p>","DOI":"10.1113\/ep091659","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T23:01:02Z","timestamp":1736290862000},"page":"3968-3982","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Confined spaces in space: Cerebral implications of chronic elevations of inspired carbon dioxide and implications for long\u2010duration space travel"],"prefix":"10.1113","volume":"111","author":[{"given":"Jay M. J. 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