Burn injury insulin resistance and central nervous system complications: A review

• Published in: Burns open : an international open access journal for burn injuries 2020-04, Vol.4 (2), p.41-52
• Main Authors: Berlanga-Acosta, Jorge, Mendoza-Marí, Yssel, Rodríguez-Rodríguez, Nadia, García del Barco Herrera, Diana, García-Ojalvo, Ariana, Fernández-Mayola, Maday, Guillén-Nieto, Gerardo, Valdés-Sosa, Pedro A.
• Format: Article
• Language: English
• Subjects: Burn injury; Hyperglycemia; Insulin; Insulin receptor; Insulin resistance; Post-burn cognitive impairment
• ISSN: 2468-9122; 2468-9122
• DOI: 10.1016/j.burnso.2020.02.001

•Stress-related peripheral insulin resistance is a metabolic abnormality that disturbs the ability of tissues to use insulin. It is a difficult to treat complication seen in patients suffering from sepsis, severe trauma or major burns.•Insulin resistance led to post-burn reactive hyperglycemia, hyper-metabolism, and catabolism which may persist for years. Multiple converging drivers led to a “loss-of-function” of the insulin receptor axis.•Neuropathological complications are frequently described in patients with severe burns contributing to high morbidity and mortality. Neuroinflammation appears as the triggering factor for insulin resistance and eventually to neurons glucose hypometabolism.•Despite the abundant basic and clinical descriptions of insulin resistance in critical care, it is still overwhelming the number of uncertainties existing in central insulin resistance pathomechanism. Insulin resistance is a major underlying and preexisting event in chronic metabolic disorders. However, this is also an acute, de novo condition in critical burn survivors and other emergency episodes. Irrespective to its proximal trigger in burn pathology, peripheral insulin resistance results from an impaired receptor’s signaling to accurately transduce the hormonal message, leading to hyperglycemia, hypermetabolism and catabolia. Elevation of stress hormones, pro-inflammatory cytokines, along with spillover of mitochondria-derived free radicals lead to an insulin receptor impairment that counteracts insulin anabolic actions. These post-burn metabolic-inflammatory disorders could last for years and embraces the central nervous system. The persistence of these events may suggest the existence of a metabolic memory beyond that described for diabetes, in which the involvement of epigenetic mechanisms remains to be investigated. The brain is a target organ of multiple post-burn complications which seem to be set forth through peripheral/central inflammation, nitric oxide imbalance, oxidative stress, and ultimately neuronal insulin resistance and insufficient glucose utilization. From neuroses to dementia post-burn neurological complications are described as clinical expression of neuronal degeneration, apoptosis, and synapsis rupture. All these events may represent the collapse of the neuroprotective actions due to the failed insulin axis. Although peripheral and central insulin resistance may be mechanistically determined by different players, for both scenarios, mitochond