David D Fuller

Research topics

Matched from this investigator's NIH project titles and abstracts.

• Cognitive Aging
• Neuroplasticity and Neural Repair
• Learning and Memory

Active NIH awards

• Normobaric Oxygen Therapy for Spinal Cord Injury

  5R01NS139422-02

  NINDS · FY 2025 · $580K

  ABSTRACT Spinal cord injury (SCI) interrupts blood flow, and the O2 partial pressure (PO2) in the injured spinal cord drops to near zero. This contributes to necrosis and secondary injury. Our central hypothesis is that increasing O2 delivery to the injured cervical spinal cord will attenuate inflammation and neuronal cell loss, thereby preserving breathing function. The vast majority of prior O2 therapy studies after SCI use hyperbaric O2 (HBO), and there is considerable support that HBO reduces inflammation and secondary neurodegeneration. However, HBO consists of 100% O2 (hyperoxia), which is easy to implement, but at elevated pressure (hyperbaria), which is challenging to implement. Preliminary data indicate that the more challenging hyperbaria may not be needed. Specifically, normobaric hyperoxia (i.e., 100% O2 at ambient pressure) rapidly restores spinal PO2 after acute SCI and triggers anti-inflammatory mechanisms with a specific impact on microglia. Neuroinflammation after SCI contributes to scarring and neuronal loss, and impairs plasticity in spinal respiratory motor pathways. Thus, Aim 1 will determine if normobaric O2 therapy, initiated acutely (i.e., hours-days) after cervical SCI (cSCI), increases spinal PO2, mitigates microglial-driven spinal neuroinflammation, and preserves breathing ability. Preliminary data also indicate that a 1-hour per day treatment with normobaric hyperoxia has only a modest impact on secondary neuronal loss after SCI (i.e., neuroprotection). However, more robust neuroprotection can be achieved with HBO therapy. Since the fundamental difference between normo- and hyperbaric therapy is total blood O2, we predict that supplementing O2 delivery through alternate means will enable normobaric therapy to achieve greater neuroprotection. To test this idea, we will study perfluorocarbons - molecules that increase plasma O2 solubility and delivery to the injured spinal cord. Preliminary data show that treatment with a “next generation” perfluorocarbon known as NanO2 is safe, well tolerated, and preserves spinal tissues post-SCI. In Aim 2 we will test the hypothesis that combining normobaric hyperoxia with NanO2 acutely after cervical SCI synergistically increases spinal PO2, and promotes neuroprotection in primary (acute) and secondary cSCI. The proposed work will utilize our established cervical SCI models in the rat, including mid-cervical contusion and C2 hemilesion. Outcome measures include 1) cell-specific molecular responses (e.g., neurons, astrocytes and microglia) via flow cytometry, 2) spinal immunohistochemistry and histological neuron counts, 3) in vivo magnetic resonance imaging (MRI) for visualizing lesion volume, and ex vivo MRI for evaluating neural tracts in high- resolution (tractography), 4) respiratory outcomes including diaphragm EMG and breathing in unanesthetized rats, and direct measure of phrenic nerve output in anesthetized rats, and 5) spinal O2 measurements (intraspinal optode).

• Fuller T32 renewal

  5T32HD043730-22

  NICHD · FY 2025 · $300K

  ABSTRACT The Interdisciplinary Training Program in Rehabilitation and Neuromuscular Plasticity (NMPT) at the University of Florida (UF) was initiated in 2003. The overall goal of the NMPT program is to train leaders who will enable a sustainable and cutting-edge rehabilitation science infrastructure in the United States. Towards this goal, the NMPT program recruits PhD students from UF PhD programs from across the biomedical science spectrum. Trainees include individuals with clinical rehabilitation degrees as well as basic scientists with a demonstrated interest in applying their work to rehabilitation and advancing human health. Our training program is unique in that it emphasizes the interaction and joint training of rehabilitation clinicians and basic science Trainees. The program capitalizes on existing UF strengths including a core of well-established rehabilitation investigators, outstanding research facilities, strong institutional commitment, and a culture of successful mentorship in rehabilitation. The NMPT program is a well-defined, closely monitored program with clearly established training objectives and an effective evaluation process. Upon entering the program, each Trainee prepares an individualized training plan under the guidance of a Faculty Mentor and Translational Research Co-Advisor. The individualized plan consists of a structured program with courses, journal clubs and seminars, laboratory research and multiple scientific dissemination experiences. Our well-defined management structure that includes a Program Director, Education Coordinator, a Translational Science Advisor, an Internal Steering Committee and an External Advisory Board. The program draws students from five PhD programs in the biomedical sciences, and our 30 NMPT faculty all have active research funding, and have appointments in multiple UF Colleges including Public Health and Health Professions, Medicine, Engineering, and Human Health and Performance. Our program also partners with UF Centers and Institutes including those devoted to movement disorders, muscle biology, cognitive aging and memory, and exercise science. Over the last funding cycle (2018- current), the NMPT program has supported 18 Trainees including physical therapists, speech-language therapists, and basic science trainees. We are proud that our current cohort of seven Trainees includes five individuals from underrepresented minority groups. The NMPT program is achieving our goal of training scientists capable of engaging in translational rehabilitation research and sustaining independently funded research programs.