This thesis examined the role of exogenous basic fibroblast growth factor (FGF-2) in stimulating recovery after early cortical injury. Rats with medial prefrontal cortex (MFC), posterior parietal cortex (PPC), or sham lesions at postnatal day 3 (P3) received one of three variations of FGF-2 treatment: postnatal FGF-2 that was either pre-mixed or prepared daily, or prenatal FGF-2, and tested in adulthood. Behavioral tests used were: 1) the Morris Water task and, 2) the Whishaw Tray Reaching task. The level of functional recovery attained was dependent on FGF-2 preparation and the developmental period. MFC lesion rats showed good recovery but there was a differntial effect of pre and postnatal FGF-2 that appeared to be related to task. PPC rats showed greater recovery after postnatal rather than prenatal treatment. Anatomical changes were restricted to groups with relatively good functional recovery. These findings suggest a multifunctional role of FGF-2 in the injured brain. / xvi, 223 leaves : ill. ; 29 cm.

Previous work has shown that removal of the midline frontal cortex at seven to ten days of age is followed by recovery of function correlated with apparent spontaneous generation of new tissue in the lesion cavity. The question asked in the present thesis was whether the removal of the regrown tissue in adulthood would block normal function. Rats that received P10 frontal lesions underwent second lesions at P160, and were compared to rats with only P10 or P160 lesions. Rats with P10 + P160 lesions were severely impaired on a spatial learning task, especially relative to the P10 lesion-only rats. In a second experiment, rats with P10 + P160 lesions were given intra-ventricular infusions of a cocktail of three growth factors. The animals with growth factors showed marked behavioral recovery, although there was no cell regeneration. The results of these experiments suggest that filled-in tissue in neonatally lesioned rats is functional. / viii, 74 leaves : col. ill. ; 28 cm.

The current work explores the behavioural and anatomical consequences of unilateral neonatal bulbectomy (OBX) in male and female rats at postnatal day 1 (PI) and P10. In adulthood the animals underwent a battery of motor and cognitive tests, and diffuse effects of early brain injury on the development of behavior were found. Disturbing olfactory sense input during development affected motor output. Rats normally display an equal distribution of right or left paw preference. In this study, both OBX sexes showed a shifted paw preference to the ipsilesional side, and forelimb deficits were found in a skilled reaching task. Lesion animals also showed enhanced performance on a visually driven spatial cognitive test. Cross-modal compensatory changes may be responsible. Morphological changes within the cerebral cortex are described, including bulbar changes, enlarged but fewer glomeruli, smaller accessory olfactory bulb, decreased downstream connectivity, and a rostral shift of the forebrain toward the olfactory bulb. Changes to the lateral cortex were found in both intact and lesion hemispheres, along with dendritic changes in the forelimb reaching area. Cellular regeneration within the lesion bulb was indicated. Changed shape and relative size increases compared to the intact bulb were found. BrdU labeling showed increased mitotic activity in P10 lesion animals. These findings demonstrate that the impact of olfactory injury during early development goes well beyond odor perception and discrimination, and that olfactory inputs during development significantly contribute to the development of the neocortex. / xix, 195 leaves : ill. (some col.) ; 29 cm.

No description available.

The relationship between lesion volume in children with traumatic brain injury (TBI) and IQ scores was investigated in this study. Participants included eight children between the ages of 8-12 years with primarily right hemisphere TBIs and 16 normals who were matched based on age and gender. Archival data employing the Wechsler Intelligence Scale for Children - III (WISC-III) scores was the source of Verbal IQ (VIQ), Performance IQ (PIQ), and Full Scale IQ (FSIQ) scores. Severity of injury was determined using the Glasgow Coma Scale (GCS) which was contained in the same archival database. Lesion volume was determined utilizing National Institute of Health (NIH) Image (Version 1.76) and magnetic resonance imaging scans of the injured children. The area of the lesion was outlined, using the freehand line tool, on successive slices, summed, and multiplied by the corresponding acquisition slice gap to obtain a measure of total volume. Results indicated that lesion volume does not explain a significant portion of the variance associated with TBI. Severely injured children had lower IQs than children with mild or no injury. Additionally, children with right hemisphere injuries had significantly lower VIQ, PIQ, and FSIQ scores than normals. Qualitative analyses revealed that lesion volume appears to be related to the change in IQ scores during recovery. Typically, children with larger lesions (e.g., more severe injury) had greater functional losses and had greater gains to make; therefore, they demonstrated greater changes in IQ score as compared to less severely injured children. Predicting the area of deficit based upon lesion location yielded results congruent with chance. Results appear to reinforce the complexity of TBI; no single piece of data explains a significant portion of the variance associated with this phenomenon. Future research should strive toExamine and control for the numerous factors associated with TBI (e.g., age, lesion location, lesion volume, premorbid abilities, parental education, GCS score, gender, use of standard test battery, and many others) within a single study. Efforts to provide optimal treatment and recovery of TBI patients could be informed by such research. / Department of Counseling Psychology and Guidance Services

Access to abstract permanently restricted to Ball State community only. / Department of Counseling Psychology and Guidance Services

Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: LaPlaca, Michelle; Committee Member: Bellamkonda, Ravi; Committee Member: Garcia, Andres; Committee Member: Hochman, Shawn; Committee Member: Wang, Yadong. Part of the SMARTech Electronic Thesis and Dissertation Collection.

One of the consequences of traumatic brain injury is the postconcussion syndrome. The symptoms in this syndrome include headache, dizziness, poor memory, poor concentration, easy fatigue, drowsiness, irritability, sensitivity to light, sensitivity to noise, low alcohol tolerance, visual problems, auditory problems, nausea, vomiting, anxiety, and depression. Several factor analytic studies have shown that these symptoms load onto cognitive and noncognitive factors (Bohnen, Twijnstra, & Jolles, 1992). The aim of this study was to determine whether patients who report different symptoms also evidence differences in cognitive deficits, as indexed by reaction time. For this purpose 106 subjects (mean age 25.92 years; SD=6.05) of both sexes were tested on 8 reaction time tasks adapted from Shum, McFarland, Bain, and Humphreys (1990). There were 54 traumatic brain injury patients (mean age 26.40 years; SD=6.23) drawn from three Pretoria hospitals. They were heterogeneous with respect to diagnosis and severity of injury. For the controls (N=52), the mean age was 25.43 years (SD=5.88). The eight reaction time tasks constituted 4 task variables, each with 21evels. From these tasks, 36 reaction time indexes were derived. The indexes were classified into 4 groups, viz., reaction time (RT), movement time (MT), total reaction time (TT), and subtraction scores (SB, the difference between the 2 levels for each task variable). RT reflects the decision component and MT reflects the response execution component of reaction time. Partial correlation coefficients for all symptoms (p0,01) showed that some symptoms were most frequently associated with RT whilst others were most frequently associated with MT. On factor analysis with varimax rotation, symptoms loaded predominantly with SB scores. Symptoms also loaded with different task variablseuiggesting that they correlated with deficits on different stages of information processing. Taking into account possible methodological constraints that were discussed, these results confirm that different symptoms within the postconcussion syndrome correlate with different cognitive deficits. The correlations between symptoms and indices of reaction time are moderated by the characteristics of the symptoms (frequency & intensity), and the duration since injury. These findings have significance for understanding the aetiology of the postconcussion symptoms and for planning treatment. / Psychology / Ph. D. (Psychology)

This descriptive exploratory study was designed to determine the perceived importance of selected needs of family members of critically ill brain-injured patients. In addition, the personal/demographic factors which may have influenced the needs of these family members were investigated, as well as the reasons family members perceived these needs as important or unimportant. A convenience sample of one family member for each of 15 critically ill brain-injured patients was selected from two tertiary care hospitals and the community. Family members were interviewed using a pre-determined interview guide and asked to verbally rate 20 need statements on a four-point Likert-type scale. Generally, family members perceived all 20 needs to be important. However, the importance of each need was influenced by the family members' personal/demographic factors. No significant statistical relationship was found between personal/demographic factors and the family members' perceptions of the importance of selected needs. However, the findings of the study suggest that family members relate their needs to their present experience, and thus individual assessment of family members' needs is crucial. / Applied Science, Faculty of / Nursing, School of / Graduate

Neurodegenerative diseases are highly multifaceted. Despite their heavy burden, treatment options are limited and our understanding of their molecular triggers even less so. In this thesis, I focus on the pathogenesis of Alzheimer’s Disease (AD) due to familial, sporadic and environmental causes. Previous research shows that early AD stages are characterized by upregulated functionality of mitochondria-associated endoplasmic reticulum (ER) membranes. These “MAM” domains of the ER are dynamic contacts between the ER and mitochondria distinguished by a unique lipid composition equivalent to a lipid raft. These sites cluster a specific set of metabolic enzymes that regulate cellular lipid uptake, trafficking and turnover. We find that cleavage of the amyloid precursor protein at MAM domains is intimately involved in MAM regulation through localization of its C-terminal fragment of 99 a.a., C99, to MAM regions. C99 upregulates MAM functionality by promoting cholesterol uptake and trafficking to the ER for esterification, observable in both familial and sporadic AD samples. Here, we recapitulated these phenotypes in a mouse model of an environmental AD trigger: traumatic brain injury (TBI). Through biochemical, transcriptional and lipidomic analyses, we observed MAM functionality to be upregulated following a single brain injury. This was determined by assessment of phospholipid synthesis and cholesterol esterification. This correlated with increased deposition of C99 in MAM domains as well as cell type-specific lipidomic alterations. Specifically, cholesterol esterification was predominant in microglia, triglyceride elevations were predominant in microglia and astrocytes, and polyunsaturated phospholipid elevations were predominant in neurons. We hypothesize that, in the acute phase, MAM upregulation serves to promote lipid synthesis for tissue repair. However, if these phenotypes are sustained (such as after multiple injuries), cognitive functions dependent on neuronal functionality could become compromised. Altogether, we propose that the induction of AD pathogenesis following brain injury may arise from chronic upregulation of MAM activities. This work advances our understanding of neurodegenerative disease etiology.