The potential role of carbon dioxide in the neuroimmunoendocrine changes following cerebral ischemia.

Carbon dioxide (CO(2)) interacts in complex ways with the brain and the endocrine and immune systems. Arterial CO(2) may be elevated or decreased following cerebral ischemia-reperfusion injury or stroke. The aim of the present review is to delineate potential changes in the neuroimmunoendocrine system following cerebral ischemia-reperfusion injury and to provide evidence for the modulatory role of carbon dioxide in this setting. It appears that lesions of the right and left cerebral hemispheres are associated with different patterns of immune activation and cytokine release. Changes in arterial CO(2) can profoundly alter the neuroimmunoendocrine system, especially the hypothalamic-pituitary-adrenal (HPA) axis and the production of pro-inflammatory cytokines. Hypercapnia activates the HPA axis, exerts antiinflammatory and antioxidant effects, and can alter the secretion and function of various brain neurotransmitters. There is conflicting evidence surrounding arterial CO(2): its effects on the ischemic brain may be either beneficial or deleterious. Mild hypercapnia may exert some neuroprotection following cerebral ischemia, but severe hypercapnia may aggravate neuronal injury by extra- and intra-cellular acidification and/or impairment of cellular calcium hemostasis. Future studies are required to delineate the potential relationship between arterial CO(2) and prognosis and long-term survival following cerebral ischemia-reperfusion injury. "Therapeutic hypercapnia" seems to be a promising approach to the treatment of stroke patients, and its use should be justified by further experimental and clinical studies.