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Biochemical and neurochemical sequelae following mild traumatic brain injury: summary of experimental data and clinical implications.

Department of Neurosciences Head and Neck Surgery, San Camillo Hospital, Rome, Italy.
Neurosurgical FOCUS (Impact Factor: 2.14). 11/2010; 29(5):E1. DOI: 10.3171/2010.9.FOCUS10183
Source: PubMed

ABSTRACT Although numerous studies have been carried out to investigate the pathophysiology of mild traumatic brain injury (mTBI), there are still no standard criteria for the diagnosis and treatment of this peculiar condition. The dominant theory that diffuse axonal injury is the main neuropathological process behind mTBI is being revealed as weak at best or inconclusive, given the current literature and the fact that neuronal injury inherent to mTBI improves, with few lasting clinical sequelae in the vast majority of patients. Clinical and experimental evidence suggests that such a course, rather than being due to cell death, is based on temporal neuronal dysfunction, the inevitable consequence of complex biochemical and neurochemical cascade mechanisms directly and immediately triggered by the traumatic insult. This report is an attempt to summarize data from a long series of experiments conducted in the authors' laboratories and published during the past 12 years, together with an extensive analysis of the available literature, focused on understanding the biochemical damage produced by an mTBI. The overall clinical implications, as well as the metabolic nature of the post-mTBI brain vulnerability, are discussed. Finally, the application of proton MR spectroscopy as a possible tool to monitor the full recovery of brain metabolic functions is emphasized.

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Available from: Giuseppe Lazzarino, Oct 16, 2014
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    • "The authors have concluded that these otherwise transient changes predispose the brain for additional damage if subsequent insults take place within the period of ICV. Whether or not other components of the secondary injury process contribute to ICV as well as the exact " window period " of vulnerability have yet to be determined [5] [9]. Previous studies, including our own, have identified several of the pathobiologies involved in blast-induced TBI (bTBI), which may contribute to ICV. "
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    ABSTRACT: The consequences of a mild traumatic brain injury can be especially severe if it is repeated within the period of increased cerebral vulnerability (ICV) that follows the initial insult. To better understand the molecular mechanisms that contribute to ICV, we exposed rats to different levels of mild blast overpressure (a total of 5 exposures; total pressure range: 15.54–19.41 psi or 107.14–133.83 kPa) at a rate of 1 per 30 min, monitored select physiological parameters, and assessed their behavior. Two days post-injury or sham, we determined changes in protein biomarkers related to various pathologies in behaviorally relevant brain regions and in the plasma. We found that oxygen saturation and heart rate were transiently depressed following mild blast exposure and that injured rats exhibited significantly increased anxiety- and depression-related behaviors. Proteomic analyses of the selected brain regions showed evidence of substantial oxidative stress and vascular changes, altered cell adhesion, and inflammation predominantly in the prefrontal cortex. Importantly, these pathological changes as well as indications of neuronal and glial cell loss/damage were also detected in the plasma of injured rats. Our findings illustrate some of the complex molecular changes that contribute to the period of ICV in repeated mild blast-induced traumatic brain injury. Further studies are needed to determine the functional and temporal relationship between the various pathomechanisms. The validation of these and other markers can help to diagnose individuals with ICV using a minimally invasive procedure and to develop evidence-based treatments for chronic neuropsychiatric conditions.
    12/2013; 3. DOI:10.1016/j.trprot.2013.11.001
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    • "(Lee et al., 1999; Aoyama et al., 2008; Signoretti et al., 2010 "
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    ABSTRACT: The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI) and the use of (13)C labeled substrates and nuclear magnetic resonance (NMR) spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how (13)C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. (13)C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP) activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from (13)C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle.
    Frontiers in Neuroenergetics 10/2013; 5:8. DOI:10.3389/fnene.2013.00008
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    • "Neuropsychological tests such as automated neuropsychological assessment metrics (ANAM) and Immediate Post-Concussion Assessment and Cognitive Testing (ImPact) are widely used in athletics as assessment tools for mTBI, although these current clinical measures show no correlation in either detecting neurocognitive deficits beyond 10 days post-injury, or in predicting the development of post-concussive syndrome (PCS; Williams et al., 2010). Overall, current clinical tools cannot detect the subtle underlying causes of persistent neurocognitive and/or motor deficits in mTBI (Belanger et al., 2005; Signoretti et al., 2010). The concept of a default mode network (DMN), originally introduced in 2001 by Raichle and associates, has rapidly become a central theme in contemporary cognitive and clinical neuroscience. "
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    ABSTRACT: We hypothesize that the evolution of mild traumatic brain injury (mTBI) may be related to differential effects of a concussive blow on the functional integrity of the brain default mode network (DMN) at rest and/or in response to physical stress. Accordingly, in this resting-state functional magnetic resonance imaging (fMRI) study, we examined 14 subjects 10±2 days post-sports-related mTBI and 15 age-matched normal volunteers (NVs) to investigate the possibility that the integrity of the DMN is disrupted at the resting state and/or following the physical stress test. First, all mTBI subjects were asymptomatic based upon clinical evaluation and neuropsychological (NP) assessments prior to the MRI session. Second, the functional integrity within the DMN, a main resting-state network, remained resilient to a single concussive blow. Specifically, the major regions of interest (ROIs) constituting the DMN (e.g., the posterior cingulate cortex [PCC]/precuneus area, the medial prefrontal cortex [MPFC], and left and right lateral parietal cortices [LLP and RLP]) and the connectivity within these four ROIs was similar between NVs and mTBI subjects prior to the YMCA physical stress test. However, the YMCA physical stress test disrupted the DMN, significantly reducing the magnitude of the connection between the PCC and left lateral parietal ROI, and PCC and right lateral parietal ROI, as well as between the PCC and MPFC in mTBI subjects. Thus while the DMN remained resilient to a single mTBI without exertion at 10 days post-injury, it was altered in response to limited physical stress. This may explain some clinical features of mTBI and provide some insight into its mechanism. This important finding should be considered by clinical practitioners when making decisions regarding return-to-play and clearing mTBI athletes for sports participation.
    Journal of neurotrauma 10/2011; 29(5):756-65. DOI:10.1089/neu.2011.2125 · 3.97 Impact Factor
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