James ley Veterans Affairs Medical Center

Tampa, FL, United States

James ley Veterans Affairs Medical Center

Tampa, FL, United States
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Rogers J.T.,USF Health Byrd Alzheimers Institute | Morganti J.M.,University of South Florida | Bachstetter A.D.,University of South Florida | Hudson C.E.,James ley Veterans Affairs Medical Center | And 7 more authors.
Journal of Neuroscience | Year: 2011

The protective/neurotoxic role of fractalkine (CX3CL1) and its receptor CX3C chemokine receptor 1 (CX3CR1) signaling in neurodegenerative disease is an intricate and highly debated research topic and it is becoming even more complicated as new studies reveal discordant results. It appears that the CX3CL1/CX3CR1 axis plays a direct role in neurodegeneration and/or neuroprotection depending on theCNSinsult. However, all the above studies focused on the role of CX3CL1/CX3CR1 signaling in pathological conditions, ignoring the relevance of CX3CL1/CX3CR1 signaling under physiological conditions. No approach to date has been taken to decipher the significance of defects in CX3CL1/CX3CR1 signaling in physiological condition. In the present study we used CX3CR -/-, CX3CR1 +/-, and wild-type mice to investigate the physiological role of CX3CR1 receptor in cognition and synaptic plasticity. Our results demonstrate for the first time that mice lacking the CX3CR1 receptor show contextual fear conditioning and Morris water maze deficits. CX3CR1 deficiency also affects motor learning. Importantly, mice lacking the receptor have a significant impairment in long-term potentiation (LTP). Infusion with IL-1β receptor antagonist significantly reversed the deficit in cognitive functionandimpairment in LTP.Ourresults reveal that under physiological conditions, disruption in CX3CL1 signaling will lead to impairment in cognitive function and synaptic plasticity via increased action of IL-1β. © 2011 the authors.


Zhu Y.,University of South Florida | Hou H.,University of South Florida | Rezai-Zadeh K.,Regenerative Medicine Institute | Giunta B.,University of South Florida | And 15 more authors.
Journal of Neuroscience | Year: 2011

Converging lines of evidence indicate dysregulation of the key immunoregulatory molecule CD45 (also known as leukocyte common antigen) in Alzheimer's disease (AD). We report that transgenic mice overproducing amyloid-β peptide (Aβ) but deficient in CD45 (PSAPP/CD45-/- mice) faithfully recapitulate AD neuropathology. Specifically, we find increased abundance of cerebral intracellular and extracellular soluble oligomeric and insoluble Aβ, decreased plasma soluble Aβ, increased abundance of microglial neurotoxic cytokines tumor necrosis factor-α and interleukin-1β, and neuronal loss in PSAPP/CD45-/- mice compared with CD45-sufficient PSAPP littermates (bearing mutant human amyloid precursor protein and mutant human presenilin-1 transgenes). After CD45 ablation, in vitro and in vivo studies demonstrate an anti-Aβ phagocytic but proinflammatory microglial phenotype. This form of microglial activation occurs with elevated Aβ oligomers and neural injury and loss as determined by decreased ratio of anti-apoptotic Bcl-xL to proapoptotic Bax, increased activated caspase-3, mitochondrial dysfunction, and loss of cortical neurons in PSAPP/CD45 -/- mice. These data show that deficiency in CD45 activity leads to brain accumulation of neurotoxic Aβ oligomers and validate CD45-mediated microglial clearance of oligomeric Aβ as a novel AD therapeutic target. Copyright © 2011 the authors.


Stiers W.,Johns Hopkins University | Hanson S.,University of Florida | Turner A.P.,University of Washington | Stucky K.,Hurley Medical Center | And 6 more authors.
Rehabilitation Psychology | Year: 2012

Objective: This article describes the methods and results of a national conference that was held to (1) develop consensus guidelines about the structure and process of rehabilitation psychology postdoctoral training programs and (2) create a Council of Rehabilitation Psychology Postdoctoral Training Programs to promote training programs' abilities to implement the guidelines and to formally recognize programs in compliance with the guidelines. Methods: Forty-six conference participants were chosen to include important stakeholders in rehabilitation psychology, representatives of rehabilitation psychology training and practice communities, representatives of psychology accreditation and certification bodies, and persons involved in medical education practice and research. Results: Consensus guidelines were developed for rehabilitation psychology postdoctoral training program structure and process and for establishing the Council of Rehabilitation Psychology Postdoctoral Training Programs. Discussion: The Conference developed aspirational guidelines for postdoctoral education and training programs in applied rehabilitation psychology and established a Council of Rehabilitation Psychology Postdoctoral Training Programs as a means of promoting their adoption by training programs. These efforts are designed to promote quality, consistency, and excellence in the education and training of rehabilitation psychology practitioners and to promote competence in their practice. It is hoped that these efforts will stimulate discussion, assist in the development of improved teaching and evaluation methods, lead to interesting research questions, and generally facilitate the continued systematic development of the profession of rehabilitation psychology. © 2012 American Psychological Association.


Lew H.L.,Defense and Veterans Brain Injury Center | Pogoda T.K.,Virginia Commonwealth University | Hsu P.-T.,Harvard University | Cohen S.,Polytrauma and Traumatic Brain Injury Center | And 4 more authors.
American Journal of Physical Medicine and Rehabilitation | Year: 2010

Lew HL, Pogoda TK, Hsu P-T, Cohen S, Amick MM, Baker E, Meterko M, Vanderploeg RD: Impact of the "polytrauma clinical triad" on sleep disturbance in a Department of Veterans Affairs outpatient rehabilitation setting. OBJECTIVE: There is a high prevalence of Operation Enduring Freedom/Operation Iraqi Freedom veterans returning with the "polytrauma clinical triad" of pain, posttraumatic stress disorder, and traumatic brain injury. This study examined the effect of the polytrauma clinical triad on sleep disturbance, defined as difficulty falling or staying asleep, a common problem in Operation Enduring Freedom/Operation Iraqi Freedom veterans. DESIGN: A chart review was conducted for 200 Operation Enduring Freedom/Operation Iraqi Freedom veterans evaluated at a polytrauma outpatient clinic. Data that were abstracted included a sleep disturbance severity index, diagnoses of posttraumatic stress disorder and traumatic brain injury, and reported problems of pain. RESULTS: Sleep disturbance was highly prevalent (93.5%) in this sample, in which the majority of traumatic brain injury diagnoses were mild. In the multiple regression analysis, posttraumatic stress disorder, pain, the interaction of traumatic brain injury and posttraumatic stress disorder, and the interaction of posttraumatic stress disorder and pain significantly accounted for sleep disturbance. As a separate independent variable, traumatic brain injury was not associated with sleep disturbance. CONCLUSIONS:: Our preliminary results showed that posttraumatic stress disorder and pain significantly contributed to sleep disturbance. When traumatic brain injury or pain coexisted with posttraumatic stress disorder, sleep problems worsened. In this clinical population, where the majority of traumatic brain injury diagnoses tend to be in the mild category, traumatic brain injury alone did not predict sleep disturbance. Through increased awareness of pain, posttraumatic stress disorder, and traumatic brain injury, clinicians can work collaboratively to maximize rehabilitation outcomes. Copyright © 2010 by Lippincott Williams and Wilkins.


Weyna D.R.,Thar Pharmaceuticals | Cheney M.L.,Thar Pharmaceuticals | Shan N.,Thar Pharmaceuticals | Hanna M.,Thar Pharmaceuticals | And 4 more authors.
Molecular Pharmaceutics | Year: 2012

Meloxicam is a nonsteroidal anti-inflammatory drug prescribed for rheumatoid arthritis, osteoarthritis, postoperative pain and fever. Meloxicam exhibits low solubility in acidic aqueous media and a slow onset of action in biological subjects. An oral dosage form of meloxicam with enhanced aqueous solubility is desired to enable a faster onset of action and its use for mild-to-medium-level acute pain relief. With this in mind, we examine the solubility and pharmacokinetics of 12 meloxicam cocrystals with carboxylic acids. Dissolution studies of meloxicam and its cocrystals were performed in pH 6.5 phosphate buffer solutions at 37 °C. In addition, pharmacokinetic profiles over four hours were acquired after oral administration of a 10 mg/kg (meloxicam equivalent) solid suspension in rats. The majority of meloxicam cocrystals were found to achieve higher meloxicam concentrations in dissolution media and enhanced oral absorption compared to that of pure meloxicam. All meloxicam cocrystals were converted to meloxicam form I when the slurry reached equilibrium. To better understand how cocrystallization impacts the absorption of meloxicam after oral administration, correlations between the in vitro and in vivo data were explored. The results suggest that the meloxicam cocrystals with a faster dissolution rate would exhibit increased oral absorption and an earlier onset of action. © 2012 American Chemical Society.


Acosta S.A.,University of South Florida | Diamond D.M.,James ley Veterans Affairs Medical Center | Diamond D.M.,University of South Florida | Wolfe S.,James ley Veterans Affairs Medical Center | And 7 more authors.
PLoS ONE | Year: 2013

Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed cell proliferation may evolve into more severe neurodegenerative diseases and psychiatric disorders currently being recognized in traumatized TBI patients.


Acosta S.,University of South Florida | Jernberg J.,University of South Florida | Sanberg C.D.,Natura Therapeutics Inc. | Sanberg P.R.,University of South Florida | And 5 more authors.
Rejuvenation Research | Year: 2010

The process of aging is linked to oxidative stress, microglial activation, and proinflammatory factors, which are known to decrease cell proliferation and limit neuroplasticity. These factors may lead the transition from normal aging to more severe cognitive dysfunction associated with neurodegenerative diseases. We have shown that natural compounds such as polyphenols from blueberry and green tea and amino acids like carnosine are high in antioxidant and antiinflammatory activity that decreases the damaging effects of reactive oxygen species (ROS), in the blood, brain, and other tissues of the body. Furthermore, we have shown that the combination of these nutrients (called NT-020) creates a synergistic effect that promotes the proliferation of stem cells in vitro and in vivo. In the current study, we examined the effects of NT-020 on neurogenesis and performance on a Morris water maze (MWM). Aged (20-month-old) male Fischer 344 rats were treated with 135.0 mg/kg per day (n=13) of NT-020. Young (3-month-old) (n=10) and aged (20-month-old) (n=13) control male Fischer 344 rats were treated with water by oral gavage. All groups were treated for a period of 4 weeks. Although there was no difference in performance in the MWM when comparing all aged rats, when the data for aged impaired rats were compared, there was a significant difference between groups on the last day of training with the treatment group performing better than controls. Using the cell cycle-regulating protein (Ki67), doublecortin (DCX), and OX6 antibody markers, cell proliferation, neurogenesis, and microglial activation were estimated in the dentate gyrus (DG) of young and aged animals. Cell proliferation was also examined in the subventricular zone (SVZ). A decreased number of OX6 MHC II-positive cells, increased neurogenesis, and increased number of proliferating cells were found in rats treated with NT-020 in comparison with aged control rats. In sum, NT-020 may promote health, proliferation, and maintenance of neurons in the age animals and exert antiinflammatory actions that promote function in the aged stem cell niche. © 2010, Mary Ann Liebert, Inc.


Jim H.S.L.,H. Lee Moffitt Cancer Center and Research Institute | Small B.J.,H. Lee Moffitt Cancer Center and Research Institute | Small B.J.,University of South Florida | Patterson S.,H. Lee Moffitt Cancer Center and Research Institute | And 3 more authors.
Supportive Care in Cancer | Year: 2010

Goals of work: Data suggest that treatment with luteinizing hormone-releasing hormone (LHRH) agonists may be associated with reduced cognitive functioning. The purpose of the current study was to compare rates of clinically significant cognitive impairment in men treated with LHRH agonists to a matched sample of healthy men without cancer. Materials and methods: Participants were 48 men receiving LHRH agonist therapy for prostate cancer and 48 men with no history of cancer matched to patients on age and education. Participants were administered a battery of neuropsychological tests assessing the domains of verbal memory, verbal fluency, visuospatial memory, visuospatial abilities, and executive function. Clinically significant impairment on individual tests was defined as -1.5 SD below the normative mean; overall impairment was defined as impaired performance on two or more tests. Main results: Patients did not differ from comparison subjects in age, ethnicity, race, education, or annual household income (p's∈>∈0.05). No statistically significant differences in test means were found. Nevertheless, patients displayed greater overall impairment in cognitive functioning than comparison subjects (42% of patients versus 19% of comparison subjects, p∈<∈0.05). Among patients, prior prostatectomy was associated with impaired immediate and delayed verbal memory (p's∈<∈0.05). Conclusions: Current findings suggest that LHRH agonists and surgery for prostate cancer are associated with clinically significant impairment in cognitive functioning. Longitudinal studies are needed to examine changes in cognitive impairment before and after surgical and hormonal treatment for prostate cancer. Patients undergoing LHRH agonist therapy should be monitored for cognitive changes while on treatment. © 2009 Springer-Verlag.


Park D.-H.,University of South Florida | Eve D.J.,University of South Florida | Sanberg P.R.,University of South Florida | Musso J.,University of South Florida | And 8 more authors.
Stem Cells and Development | Year: 2010

It is now well accepted that the brain is able to generate newborn neurons from a population of resident multipotential neural stem cells (NSCs) located in two discrete regions of the brain. The capacity for neurogenesis appears to diminish over the lifespan of an organism. Methods to potentiate the proliferation of new neuronal or glial cells within the central nervous system from resident NSCs could have therapeutic potential following an insult, such as stroke, or to replace lost cells as a result of a neurodegenerative disease. We implanted cells from a human NSC cell line, CTX0E03, originally derived from fetal cortical tissue directly into the ventricles of aged rats. CTX0E03 cells have angiogenic properties via secretion of growth factors, so we investigated if the implanted cells would stimulate proliferation of NSCs within the subgranular zone (SGZ) of the dentate gyrus. Bromodeoxyuridine staining demonstrated significantly increased proliferation in the SGZ. Absence of double labeling for human nuclear antigen suggested that the increased proliferation was from endogenous neural progenitor cells. The acute treatment also led to an increased number of immature neurons as demonstrated by immunohistochemical staining for the immature neuronal marker doublecortin. The data suggest that implants of exogenous NSCs may promote regeneration in aging organisms through stimulation of endogenous neurogenesis. © 2010 Mary Ann Liebert, Inc.


Reinhard M.J.,War Related Illness and Injury Study Center | Reinhard M.J.,Georgetown University | Wolf G.,James ley Veterans Affairs Medical Center | Cozolino L.,Pepperdine University
Journal of Trauma and Dissociation | Year: 2010

Minnesota Multiphasic Personality Inventory (MMPI) clinical scales as well as 4 sets of MMPI items known to be sensitive to neurological dysfunction (closed head injury, cerebrovascular disorder) were administered to survivors of childhood physical and/or sexual abuse and to non-abused adults. As predicted, relative to the comparison group of psychiatric patients, the abused participants scored significantly higher on Scale 8 (Schizophrenia) and on all 4 sets of items associated with neurological dysfunction. The results suggest that early abuse/trauma is associated with cognitive disturbances and somatization. Findings appear to support the conceptualization of these psychophysical experiences as a central part of what is often called "complex posttraumatic stress disorder." Limitations and suggestions for further study are discussed. © Taylor & Francis Group, LLC.

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