Cold Environment Exacerbates Brain Pathology and Oxidative Stress Following Traumatic Brain Injuries: Potential Therapeutic Effects of Nanowired Antioxidant Compound H-290/51
Authors: Jos√© Vicente Lafuente
Aruna Sharma
Per-Ove Sj√∂quist
Hari S Sharma
Dafin F Muresanu
Ranjana Patnaik
Asya Ozkizilcik
Z Ryan Tian
Journal: Molecular Neurobiology (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Blood-brain barrier; Brain edema; Cold environment; Glutathione; H-290/51
Affiliations: Department of Surgical Sciences, Anesthesiology, and Intensive Care Medicine, Uppsala University Hospital, Uppsala University, SE-75185, Uppsala, Sweden., International Experimental CNS Injury and Repair (IECNSIR), University Hospital, Uppsala University, Fr√∂dingsgatan 12, Bldg. 28, SE-75421, Uppsala, Sweden., LaNCE, Department Neuroscience, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain., "RoNeuro" Institute for Neurological Research and Diagnostic, 37 Mircea Eliade Street, 400364, Cluj-Napoca, Romania., Department Clinical Neurosciences, University of Medicine and Pharmacy, Cluj-Napoca, Romania., Nanoneurosurgery Group, BioCruces Health Research Institute, 48903, Barakaldo, Bizkaia, Spain., Faculty of Health Science, Universidad Aut√≥noma de Chile, Santiago de Chile, Chile., Division of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., School of Biomedical Engineering, Department of Biomaterials, Indian Institute of Technology, Banaras Hindu University, Varanasi, India., Department Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR, USA., Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR, USA., Department of Surgical Sciences, Anesthesiology, and Intensive Care Medicine, Uppsala University Hospital, Uppsala University, SE-75185, Uppsala, Sweden. ., International Experimental CNS Injury and Repair (IECNSIR), University Hospital, Uppsala University, Fr√∂dingsgatan 12, Bldg. 28, SE-75421, Uppsala, Sweden. ., LaNCE, Department Neuroscience, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain. .

Abstract:  The possibility that traumatic brain injury (TBI) occurring in a cold environment exacerbates brain pathology and oxidative stress was examined in our rat model. TBI was inflicted by making a longitudinal incision into the right parietal cerebral cortex (2 mm deep and 4 mm long) in cold-acclimatized rats (5 ¬∞C for 3 h daily for 5 weeks) or animals at room temperature under Equithesin anesthesia. TBI in cold-exposed rats exhibited pronounced increase in brain lucigenin (LCG), luminol (LUM), and malondialdehyde (MDA) and marked pronounced decrease in glutathione (GTH) as compared to identical TBI at room temperature. The magnitude and intensity of BBB breakdown to radioiodine and Evans blue albumin, edema formation, and neuronal injuries were also exacerbated in cold-exposed rats after injury as compared to room temperature. Nanowired delivery of H-290/51 (50 mg/kg) 6 and 8 h after injury in cold-exposed group significantly thwarted brain pathology and oxidative stress whereas normal delivery of H-290/51 was neuroprotective after TBI at room temperature only. These observations are the first to demonstrate that (i) cold aggravates the pathophysiology of TBI possibly due to an enhanced production of oxidative stress, (ii) and in such conditions, nanodelivery of antioxidant compound has superior neuroprotective effects, not reported earlier. 

Retracted: No

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