The Pathophysiology of Concussion

Division of Neurosurgery, Department of Neurosciences Head and Neck Surgery, S. Camillo Hospital, Rome, Italy.
PM&R (Impact Factor: 1.53). 10/2011; 3(10 Suppl 2):S359-68. DOI: 10.1016/j.pmrj.2011.07.018
Source: PubMed


Concussion is defined as a biomechanically induced brain injury characterized by the absence of gross anatomic lesions. Early and late clinical symptoms, including impairments of memory and attention, headache, and alteration of mental status, are the result of neuronal dysfunction mostly caused by functional rather than structural abnormalities. The mechanical insult initiates a complex cascade of metabolic events leading to perturbation of delicate neuronal homeostatic balances. Starting from neurotoxicity, energetic metabolism disturbance caused by the initial mitochondrial dysfunction seems to be the main biochemical explanation for most postconcussive signs and symptoms. Furthermore, concussed cells enter a peculiar state of vulnerability, and if a second concussion is sustained while they are in this state, they may be irreversibly damaged by the occurrence of swelling. This condition of concussion-induced brain vulnerability is the basic pathophysiology of the second impact syndrome. N-acetylaspartate, a brain-specific compound representative of neuronal metabolic wellness, is proving a valid surrogate marker of the post-traumatic biochemical damage, and its utility in monitoring the recovery of the aforementioned "functional" disturbance as a concussion marker is emerging, because it is easily detectable through proton magnetic resonance spectroscopy.

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Available from: Giuseppe Lazzarino, Oct 16, 2014
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    • "It is speculated from recent discussion that second impact resulting from repetitive head injury (multiple concussion) may have persistence of diffuse cerebral swelling which is a mechanism of post traumatic head injury. Giza and Hovda concluded that it is difficult to state a true duration of vulnerability to second injury[10]. "

    Full-text · Article · Dec 2015
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    • "At present, very little is known about the effect of traumatic brain injury (TBI) on Ngb expression, with a few studies indicating Ngb overexpression after mechanical injury [15] and neuroprotection from TBI-associated damages in the Ngb-overexpressing animals [16]. TBI can be considered a peculiar type of acute neurodegeneration with molecular mechanisms of cell damage strictly related to the severity of injury [17] [18]. TBI is the leading cause of death under 45 years of age in Western countries [19] and carries an enormous socioeconomic burden: for example, in the United States, the annual aggregated direct medical costs and indirect costs of work loss and lost quality of life are estimated to range from $60.4 billion to $221 billion for the civilian population alone [20]. "
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    ABSTRACT: 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 a traumatic brain injury of different severity, whilst simultaneously measuring the oxidants/antioxidants 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 hours after traumatic brain injury, and the gene and protein expression of neuroglobin and the concentrations of malondialdehyde (as a parameter representative of ROS mediated damage), nitrite+nitrate (indicative of NO metabolism), ascorbate and GSH were determined in the brain tissue. Results indicated that mild traumatic brain injury, while causing a reversible increase in oxidative/nitrosative stress (increase in malondialdehyde and nitrite+nitrate) and imbalance in antioxidants (decrease in ascorbate and GSH), did not induce any change in neuroglobin. Conversely, severe traumatic brain injury caused an over 9-fold and 5-fold increase in neuroglobin gene and protein expressions respectively, as well as a remarkable increase in oxidative/nitrosative stress and depletion of antioxidants. The results of the present study, showing a lack of effect in mild traumatic brain injury, as well as an asynchronous time course changes of 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.
    Full-text · Article · Jan 2014 · Free Radical Biology and Medicine
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    • "Subsequent studies defined a window of increased vulnerability to a second injury event whereby a single moderate TBI resolved after ∼5 days, with recovery of NAA and ATP levels (Vagnozzi et al., 2007; Signoretti et al., 2011). However, when a second moderate TBI event occurred 3 days after the initial injury, then NAA and ATP levels did not recover, and outcomes were substantially poorer. "
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    ABSTRACT: N-Acetylaspartate (NAA) is employed as a non-invasive marker for neuronal health using proton magnetic resonance spectroscopy (MRS). This utility is afforded by the fact that NAA is one of the most concentrated brain metabolites and that it produces the largest peak in MRS scans of the healthy human brain. NAA levels in the brain are reduced proportionately to the degree of tissue damage after traumatic brain injury (TBI) and the reductions parallel the reductions in ATP levels. Because NAA is the most concentrated acetylated metabolite in the brain, we have hypothesized that NAA acts in part as an extensive reservoir of acetate for acetyl coenzyme A synthesis. Therefore, the loss of NAA after TBI impairs acetyl coenzyme A dependent functions including energy derivation, lipid synthesis, and protein acetylation reactions in distinct ways in different cell populations. The enzymes involved in synthesizing and metabolizing NAA are predominantly expressed in neurons and oligodendrocytes, respectively, and therefore some proportion of NAA must be transferred between cell types before the acetate can be liberated, converted to acetyl coenzyme A and utilized. Studies have indicated that glucose metabolism in neurons is reduced, but that acetate metabolism in astrocytes is increased following TBI, possibly reflecting an increased role for non-glucose energy sources in response to injury. NAA can provide additional acetate for intercellular metabolite trafficking to maintain acetyl CoA levels after injury. Here we explore changes in NAA, acetate, and acetyl coenzyme A metabolism in response to brain injury.
    Full-text · Article · Dec 2013 · Frontiers in Neuroenergetics
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