Neuroglobin expression and oxidant/antioxidant balance after graded traumatic brain injury in the rat.
Neuroglobin is a neuron-specific hexacoordinated globin capable of binding various ligands, including O2, NO, and CO, the biological function of which is still uncertain. Various studies seem to indicate that neuroglobin is a neuroprotective agent when overexpressed, acting as a potent inhibitor of oxidative and nitrosative stress. In this study, we evaluated the pathophysiological response of the neuroglobin gene and protein expression in the cerebral tissue of rats sustaining traumatic brain injury of differing severity, while simultaneously measuring the oxidant/antioxidant balance. Two levels of trauma (mild and severe) were induced in anesthetized animals using the weight-drop model of diffuse axonal injury. Rats were then sacrificed at 6, 12, 24, 48, and 120 h after traumatic brain injury, and the gene and protein expression of neuroglobin and the concentrations of malondialdehyde (as a parameter representative of reactive oxygen species-mediated damage), nitrite + nitrate (indicative of NO metabolism), ascorbate, and glutathione (GSH) were determined in the brain tissue. Results indicated that mild traumatic brain injury, although causing a reversible increase in oxidative/nitrosative stress (increase in malondialdehyde and nitrite + nitrate) and an imbalance in antioxidants (decrease in ascorbate and GSH), did not induce any change in neuroglobin. Conversely, severe traumatic brain injury caused an over nine- and a fivefold increase in neuroglobin gene and protein expression, respectively, as well as a remarkable increase in oxidative/nitrosative stress and depletion of antioxidants. The results of this study, showing a lack of effect in mild traumatic brain injury as well as asynchronous time course changes in neuroglobin expression, oxidative/nitrosative stress, and antioxidants in severe traumatic brain injury, do not seem to support the role of neuroglobin as an endogenous neuroprotective antioxidant agent, at least under pathophysiological conditions.
Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Valentina
V
Di Pietro
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Giacomo
G
Lazzarino
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Angela Maria
AM
Amorini
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Barbara
B
Tavazzi
Department of Biology, Geology, and Environmental Sciences, Division of Biochemistry and Molecular Biology, University of Catania, 95125 Catania, Italy.
Serafina
S
D'Urso
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Salvatore
S
Longo
Department of Biomedicine and Prevention, Section of Neurosurgery, University of Rome Tor Vergata, Rome, Italy.
Roberto
R
Vagnozzi
Division of Neurosurgery, Department of Neurosciences, Head and Neck Surgery, S. Camillo Hospital, Rome, Italy.
Stefano
S
Signoretti
CNR Institute of "Chimica del riconoscimento molecolare," Catholic University of Rome, Rome, Italy.
Elisabetta
E
Clementi
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Bruno
B
Giardina
Department of Biology, Geology, and Environmental Sciences, Division of Biochemistry and Molecular Biology, University of Catania, 95125 Catania, Italy. Electronic address: lazzarig@unict.it.
Giuseppe
G
Lazzarino
Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Antonio
A
Belli
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005914:Globins / Q000096:biosynthesis* / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D000078787:Neuroglobin; D015538:Nitrosation; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D016877:Oxidants; D017382:Reactive Oxygen Species; D005914:Globins; D005978:Glutathione
Brain antioxidants; Free radicals; Neuroglobin; Neuroprotection; Nitrosative stress; Oxidative stress; Traumatic brain injury