Journal of neurotrauma
-
Journal of neurotrauma · Jan 2017
ReviewGlutamate neurotransmission in rodent models of traumatic brain injury.
Traumatic brain injury (TBI) is a leading cause of death and disability in people younger than 45 and is a significant public health concern. In addition to primary mechanical damage to cells and tissue, TBI involves additional molecular mechanisms of injury, termed secondary injury, that continue to evolve over hours, days, weeks, and beyond. The trajectory of recovery after TBI is highly unpredictable and in many cases results in chronic cognitive and behavioral changes. ⋯ Diffusion of glutamate outside the synapse due to impaired uptake may lead to increased extrasynaptic glutamate signaling, secondary injury through activation of cell death pathways, and loss of fidelity and specificity of synaptic transmission. Coordination of glutamate release and uptake is critical to regulating synaptic strength, long-term potentiation and depression, and cognitive processes. In this review, we will discuss dysregulation of extracellular glutamate and glutamate uptake in the acute stage of TBI and how failure to resolve acute disruptions in glutamate homeostatic mechanisms may play a causal role in chronic cognitive symptoms after TBI.
-
Journal of neurotrauma · Jan 2017
Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.
The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). ⋯ The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics.
-
Journal of neurotrauma · Jan 2017
Inhibition of Endocannabinoid Degradation Improves Outcomes from Mild Traumatic Brain Injury: A Mechanistic Role for Synaptic Hyperexcitability.
Traumatic brain injury (TBI) is an increasingly prevalent condition affecting soldiers, athletes, and motor vehicle accident victims. Unfortunately, it currently lacks effective therapeutic interventions. TBI is defined as a primary mechanical insult followed by a secondary cascade involving inflammation, apoptosis, release of reactive oxygen species, and excitotoxicity, all of which can cause synaptic changes, altered neuronal signaling, and, ultimately, behavioral changes. ⋯ JZL184 administration significantly attenuated the increased pGluR1S845/GluR1 and pERK 1/2/ERK and the increases in miniature excitatory postsynaptic potential (mEPSC) frequency and amplitude observed in layer 5 pyramidal neurons at 10 days post-TBI. These results suggest a neuroprotective role for ECs in ameliorating the TBI-induced neurobehavioral, neuroinflammatory, and glutamate dyshomeostasis from mTBI. Further studies elucidating the cellular mechanisms involved are warranted.
-
Journal of neurotrauma · Jan 2017
Greater attention to task-relevant threat due to orbitofrontal lesion.
Injury to the orbitofrontal cortex (OFC) is a frequent consequence of head injury and may lead to dysfunctional regulation of emotional and social behavior. Dysfunctional emotional behavior may partly be related to the role of the OFC in emotion-attention interaction, as reported previously. In order to better understand its role in emotion-attention and emotion-cognitive control interactions, we investigated attention allocation to task-relevant and task-irrelevant threat-related emotional stimuli during a task requiring cognitive control in patients with lesion to the OFC. ⋯ This study provides new evidence for the role of the OFC in emotion-attention and emotion-cognitive control interactions. Further, the OFC seems to contribute to the balance between voluntary and involuntary attention networks in context of emotional stimuli. Better understanding of alterations in emotion-attention interaction offers insight into affective dysfunction due to OFC lesion.
-
Journal of neurotrauma · Jan 2017
Consistency of Self-reported Concussion History in Adolescent Athletes.
Relying on self-reported concussion injury history is common in both clinical care and research. However, young athletes may not provide consistent medical information. To date, little is known about the reliability of self-reported concussion history in high school students. ⋯ Only a small proportion of student athletes provided inconsistent concussion histories. Male gender, ADHD, and greater number of baseline concussions were significantly associated with inconsistency in reporting. Overall, these findings suggest that student athletes are quite consistent when reporting their concussion history when surveyed twice during high school.