Browsing by Subject "Brain Injuries"
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Item Activation of early neural progenitors is required for traumatic brain injury-induced hippocampal neurogenes(2008-09-19) Yu, Tzong-Shiue; Kernie, Steven G.Traumatic brain injury (TBI) is the most common form of acquired brain injury in both children and adults in the United States. TBI causes neuronal loss and results in a variety of neurological impairments and deficits in hippocampus-dependent functions. However, cognitive recovery commonly occurs though the mechanism is unknown. Exploration of post-natal neurogenesis in the hippocampus raises the possibility that adult-born neurons may contribute to cognitive recovery from TBI. Several studies in animal models that mimic TBI demonstrate there is enhanced generation of adult-born neurons in the dentate gyrus and those adult-born neurons may correlate with cognitive recovery. Due to the limits of current methodology in studying neurogenesis, it remains unclear what relevance injury-induced neurogenesis may have in the recovery process following TBI. In order to explore the relevance of injury-induced neurogenesis, I have characterized a previously generated transgenic mouse line that has rtTA-IRES-eGFP expression under the control of a nestin promoter and also contains a neural progenitor-specific regulatory element. By using this line, I have demonstrated that eGFP-expressing cells represent early neural progenitors in the adult dentate gyrus. Performing unilateral controlled cortical injury (CCI) demonstrates that this injury depletes doublecoritn (Dcx)-expressing late neural progenitors while activating eGFP-expressing early neural progenitors. To address whether the subsequent recovery of Dcx-expressing late progenitors was derived from activation of early neural progenitors, I generated a transgenic line that expresses modified herpes simplex viral thymidine kinase (delta-HSV-TK) under the control of the neural progenitor-specific regulatory element of the nestin gene. This allows for temporally regulated ablation of dividing neural progenitors by exposing the animal to ganciclovir. Using this line, I demonstrate that ablation of dividing GFP-expressing early neural progenitors in neurogenic areas occurs only in the presence of ganciclovir. CCI on these mice, reveals that no newly born Dcx-expressing late neural progenitors are observed seven days after injury when exposed to ganciclovir. However, the repopulation of Dcx-expressing cells is apparent when ganciclovir was removed one day before injury. Four weeks after injury, those newly born Dcx-expressing cells became mature NeuN-expressing neurons. This suggests that injury-induced activation of early neural progenitors is required for the recovery of injured hippocampal neurons.Item Connectivity within the Default Mode Network after Traumatic Axonal Injury(2011-12-12) Arenivas, Ana; Marquez de la Plata, CarlosTraumatic axonal injury (TAI) is a common consequence of TBI in which the brain’s white matter is mechanically torn by deceleration and rotational forces. Injury to axons after this type of injury causes significant impairments in cognitive functioning, but the association between disruption of structural connections (i.e., axons) and the brain’s functional connectedness is not well understood. Studies examining integrity of white matter after TAI have found significant compromise to structures likely involved in the connectivity of the default mode network (DMN), a reliably elicited functional neural network with clinical implications. The discriminant and prognostic utilities of the DMN following traumatic axonal injury (TAI) have not been previously investigated. This broad investigation was comprised of two related studies examining the utility of neuroimaging modalities as biomarkers of TAI. Resting-state magnetic resonance imaging (RS-MRI) and diffusion tensor imaging (DTI) sequences were acquired 6-11 months post-injury using a 3T scanner from 25 patients with TAI and 17 controls. Functional and neurocognitive outcomes were assessed the same day. The first study examined the utility of three approaches analyzing DMN integrity using RS-fMRI. The purpose was to identify the utility of each approach to distinguish between healthy and brain-injured individuals, and determine whether observed differences have clinical significance. The second study integrated functional and structural connectivity measures of the DMN to determine whether compromise to functional connectivity within this network can be explained by the degree of white matter compromise commonly observed after TAI. The first study concluded that connectivity within the DMN is compromised after TAI, as all three methods demonstrated good ability to discriminate between healthy and injured brains. The second study suggests the functional disconnectedness within the DMN is in part due to compromise in structural connections observed after TAI. Neither the degree of functional or structural compromise to the DMN has clinical implications in TAI. In general, the two investigations suggest the DMN undergoes compromise after TAI, and connectivity between nodes of the network are valid markers of axonal injury.Item Working Memory Differences in Pediatric Moderate and Severe Traumatic Brain Injury(2010-01-12T18:51:39Z) Fitzpatrick, Stephanie Ann; Stavinoha, PeterTraumatic brain injury is one of the leading causes of disability and impairment in children and adolescents. This study sought to determine the effects of severity on verbal working memory and verbal short-term memory. It was hypothesized that increased severity of injury would be associated with decreased performance on working memory tasks. Participants, aged 6-16 years, were tested 6 to 12 months after injury. The sample was comprised of 12 children and adolescents who had sustained a severe TBI and 11 children and adolescents who had sustained a moderate TBI. Results indicated that there were no significant differences between the moderately injured group and subjects with severe injuries on tasks of verbal working memory or verbal short-term memory. However, inspection of the data indicated that children in the severe group performed in the Low Average range, while children in the moderate group performed in the Average range. Results may be limited by the small sample size. [Keywords: traumatic brain injury; pediatric traumatic brain injury; working memory; working memory in pediatric TBI; working memory after TBI]