A5058378714- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Spinal Cord Injury Research
- Pluripotent Stem Cells Research
- Nerve Injury and Rehabilitation
- Mesenchymal stem cell research
- Tissue Engineering and Regenerative Medicine
- Biomedical Ethics and Regulation
- Cardiovascular Issues in Pregnancy
- Neurogenetic and Muscular Disorders Research
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- Amyotrophic Lateral Sclerosis Research
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Spinal Dysraphism and Malformations
- Axon Guidance and Neuronal Signaling
- Signaling Pathways in Disease
- Infectious Aortic and Vascular Conditions
- Nuclear Receptors and Signaling
- Blood properties and coagulation
- Aortic Disease and Treatment Approaches
- Zebrafish Biomedical Research Applications
- Hereditary Neurological Disorders
- Muscle Physiology and Disorders
University of California, San Diego
2015-2024
VA San Diego Healthcare System
2016-2024
United States Department of Veterans Affairs
2011-2022
Jiangsu Hengrui Medicine (China)
2021
Paul Hastings
2015
Washington University in St. Louis
2011
Differentiation of stem cells toward a neuronal lineage normally involves gradually progressive restriction in developmental potential and is regulated by diverse set specific temporally precise genetic events. However, recent studies have indicated that both rodent human bone marrow stromal (MSCs) can be rapidly (within minutes to hours) induced differentiate into neurons vitro relatively simple chemical means (using beta-mercaptoethanol [BME] or dimethylsulfoxide [DMSO] butylated...
Previous attempts to promote regeneration after spinal cord injury have succeeded in stimulating axonal growth into or around lesion sites but rarely beyond them. We tested whether a combinatorial approach of the neuronal cell body with cAMP and injured axon neurotrophins would propel injury. A preconditioning stimulus sensory bodies was delivered by injecting L4 dorsal root ganglion, postinjury administered neurotrophin-3 (NT-3) within cervical site grafted autologous bone marrow stromal...
Abstract To examine neuroanatomical mechanisms underlying fine motor control of the primate hand, adult rhesus monkeys underwent injections biotinylated dextran amine (BDA) into right cortex. Spinal axonal anatomy was examined using detailed serial‐section reconstruction and modified stereological quantification. Eighty‐seven percent corticospinal tract (CST) axons decussated in medullary pyramids descended through contralateral dorsolateral spinal cord. Eleven CST projected ipsilateral to...
We subjected rats to either partial midcervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into beyond the lesion. Subjects received cAMP injections brainstem reticular neurons stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites provide permissive matrices for growth, brain-derived neurotrophic factor gradients distal of axons. Findings were compared with several...
Neural progenitor cell (NPC) transplantation has high therapeutic potential in neurological disorders. Functional restoration may depend on the formation of reciprocal connections between host and graft. While it been reported that axons extending out neural grafts brain form contacts onto phenotypically appropriate target regions, is not known whether adult, injured regenerating into NPC also connections. We report spinal cord NPCs grafted adult rat self-assemble organotypic, dorsal...
Neural stem cells (NSCs) differentiate into both neurons and glia, strategies using human NSCs have the potential to restore function following spinal cord injury (SCI). However, time period of maturation for in adult injured CNS is not well defined, posing fundamental questions about design implementation NSC-based therapies. This work assessed H9 that were implanted sites SCI immunodeficient rats over a 1.5 years. Notably, grafts showed evidence continued entire assessment period. Markers...
Neural progenitor cell grafts form new relays across sites of spinal cord injury (SCI). Using a panel neuronal markers, we demonstrate that neural to rodent SCI adopt diverse motor and sensory interneuronal fates, representing most subtypes the intact cord, spontaneously segregate into domains distinct clusters. Host corticospinal axons regenerating innervate appropriate pre-motor interneurons, based on trans-synaptic tracing with herpes simplex virus. A human graft non-human primate also...
Abstract Neurotrophic factors exert many effects on the intact and lesioned adult central nervous system (CNS). Among these are prevention of neuronal death (neuro troph ism) promotion axonal growth trop after injury. To date, however, it has not been established whether survival functions neurotrophins can be independently modulated in injured neurons vivo. address this question, ability brain‐derived neurotrophic factor (BDNF) to influence corticospinal motor was examined two injury...
Neurogenesis has been described in various regions of the CNS throughout life. We examined extent natural cell division and replacement from 7 weeks to months after cervical spinal cord injury four adult rhesus monkeys. Bromodeoxyuridine (BrdU) injections revealed an increase >80-fold number newly divided cells primate injury, with average 725,000 BrdU-labeled identified per monkey immediate zone. By 15% these new expressed mature markers oligodendrocytes 12% astrocytic markers. Newly...
Olfactory ensheathing cells (OECs) have been reported to migrate long distances and bridge lesion sites, guiding axonal regeneration after spinal cord injury (SCI). To understand mechanisms of OEC migration guidance, we injected lamina propria OECs 1 mm rostral caudal C4 SCI sites. One month later, formed an apparent migrating cell tract continuously extending from the injection site through lesion, physically bridging lesion. Confocal immunolabeling demonstrated that, whereas this displaced...
Changes in the molecular and cellular composition of CNS after injury or disease result formation an inhibitory environment that inhibits regeneration adult mammalian neurons. Although a dramatic change traumatic is hemorrhage because vascular rupture leakage blood-brain barrier, potential role for blood proteins repair processes remains unknown. Here we show protein fibrinogen inhibitor neurite outgrowth massively deposited spinal cord injury. We acts as ligand beta3 integrin induces...