A5065656870- Nerve injury and regeneration
- Spinal Cord Injury Research
- Neurogenesis and neuroplasticity mechanisms
- Pain Mechanisms and Treatments
- Nerve Injury and Rehabilitation
- Axon Guidance and Neuronal Signaling
- Interprofessional Education and Collaboration
- Signaling Pathways in Disease
- Proteoglycans and glycosaminoglycans research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Interference and Gene Delivery
- Healthcare Quality and Management
- Adenosine and Purinergic Signaling
- Immune Response and Inflammation
- Zebrafish Biomedical Research Applications
- Transcranial Magnetic Stimulation Studies
- Health Policy Implementation Science
- Mental Health and Patient Involvement
- Pluripotent Stem Cells Research
- Nicotinic Acetylcholine Receptors Study
- Ion channel regulation and function
- Infectious Aortic and Vascular Conditions
- Aortic Disease and Treatment Approaches
- Nursing Roles and Practices
- Neuroscience of respiration and sleep
King's College London
2014-2023
King's College - North Carolina
2021
The Royal Melbourne Hospital
2020
Charles University
2018
University of Birmingham
2018
Wolfson Foundation
2017
Digital Research Alliance of Canada
2013-2017
University of Salford
2014
Center for Advancing Health
2013
Health Foundation
2011
Central sensitization, the hyperexcitability of spinal processing that often accompanies peripheral injury, is a major component many persistent pain states. Here we report neurotrophin, brain-derived neurotrophic factor (BDNF), modulator excitability within cord and contributes to mechanism central sensitization. BDNF, localized in primary sensory neuron cell bodies terminals, potentiates nociceptive reflex responses an vitro preparation induces c-fos expression dorsal horn neurons. NMDA...
Chondroitin sulfate proteoglycans (CSPGs) are inhibitory extracellular matrix molecules that upregulated after CNS injury. Degradation of CSPGs using the enzyme chondroitinase ABC (ChABC) can promote functional recovery spinal cord However, mechanisms underlying this not clear. Here we investigated effects ChABC treatment on promoting plasticity within cord. We found robust sprouting both injured (corticospinal) and intact (serotonergic) descending projections as well uninjured primary...
Abstract Injury to the central nervous system (CNS) alters molecular and cellular composition of neural tissue leads glial scarring, which inhibits regrowth damaged axons. Mammalian scars supposedly form a chemical mechanical barrier neuronal regeneration. While tremendous effort has been devoted identifying characteristics scar, very little is known about its properties. Here we characterize spatiotemporal changes elastic stiffness injured rat neocortex spinal cord at 1.5 three weeks...
Chondroitin sulfate proteoglycans (CSPGs) inhibit repair following spinal cord injury. Here we use mammalian-compatible engineered chondroitinase ABC (ChABC) delivered via lentiviral vector (LV-ChABC) to explore the consequences of large-scale CSPG digestion for repair. We demonstrate significantly reduced secondary injury pathology in adult rats contusion and LV-ChABC treatment, with cavitation enhanced preservation neurons axons at 12 weeks postinjury, compared control (LV-GFP)-treated...
Brain-derived neurotrophic factor (BDNF) is synthesized by small neuron cell bodies in the dorsal root ganglia (DRG) and anterogradely transported to primary afferent terminals horn where it involved modulation of painful stimuli. Here we show that BDNF released rat isolated after chemical stimulation capsaicin or electrical roots. Capsaicin superfusion (1–100 μ m ) induced a dose-dependent release BDNF, measured using ELISA. The highest dose also depletion protein horn. was seen roots at...
Abstract The regeneration capacity of spinal cord axons is severely limited. Recently, much attention has focused on promoting descending pathways, but little known about the regenerative ascending axons. Here we have assessed ability neurotrophic factors to promote sensory neurons whose central ascend in dorsal columns. columns adult rats were crushed and either brain‐derived factor (BDNF), glial cell line‐derived (GDNF), neurotrophin‐3 (NT‐3) or a vehicle solution was delivered...
Mounting evidence supports the hypothesis that spinal microglia modulate development and maintenance of some chronic pain states. Here we examined role following both peripheral inflammatory insult nerve injury. We observed significant ipsilateral dorsal horn activation 2 weeks after injury bilateral 50 days as well 24 h intraplantar zymosan but not complete Freund's adjuvant (CFA). Ipsilateral contralateral was associated with hind paw mechanical hyperalgesia. Spinal injection glial...
Loss of function is usually considered the major consequence spinal cord injury (SCI). However, pain severely compromises quality life in nearly 70% SCI patients. The principal aim this study was to assess contribution Tumor necrosis factor alpha (TNF-alpha) pain. TNF-alpha blockers have already been successfully used treat inflammatory disorders but there are few studies on its effect neuropathic pain, especially following SCI. Following T13 hemisection, we examined effects mechanical...
In the majority of spinal cord injuries (SCIs), some axonal projections remain intact. We examined functional status these surviving axons since they represent a prime therapeutic target. Using novel electrophysiological preparation, adapted from techniques used to study primary demyelination, we quantified conduction failure across SCI and studied changes over time in adult rats with moderate severity contusion (150 kdyn; Infinite Horizon impactor). By recording antidromically activated...
Chondroitinase ABC is a promising preclinical therapy that promotes functional neuroplasticity after CNS injury by degrading extracellular matrix inhibitors. Efficient delivery of chondroitinase to the injured mammalian spinal cord can be achieved viral vector transgene delivery. This approach dramatically modulates pathology and restores sensorimotor functions. However, clinical development this limited lack ability exert control over gene expression. Prior experimental regulation platforms...
Abstract Chondroitin sulfate proteoglycans (CSPGs) act as potent inhibitors of axonal growth and neuroplasticity after spinal cord injury (SCI). Here we reveal that CSPGs also play a critical role in preventing inflammation resolution by blocking the conversion pro-inflammatory immune cells to pro-repair phenotype rodent models SCI. We demonstrate enzymatic digestion CSPG glycosaminoglycans enhances cell clearance reduces protein gene expression profiles at key time points. Analysis...
Glial cell line‐derived neurotrophic factor (GDNF) and nerve growth (NGF) are neuroprotective for subpopulations of sensory neurons thus candidates pain treatment. However, delivering these factors to damaged will invariably result in undamaged systems also being treated, with possible consequences processing. In the purinergic receptor P2X 3 is found predominantly GDNF‐sensitive nociceptors. ATP signalling via may contribute pathological pain, suggesting an important role this regulating...
The expression and function of the 8 distinct catalytic isoforms PI 3-kinase (PI3K) in nervous system are unknown. Whereas most PI3Ks have a broad tissue distribution, tyrosine kinase-linked p110δ isoform has previously been shown to be enriched leukocytes. Here we report that is also highly expressed system. Inactivation mice did not affect gross neuronal development but led an increased vulnerability dorsal root ganglia neurons exhibit growth cone collapse decreases axonal extension. Loss...