A5017270693- Spinal Cord Injury Research
- Nerve injury and regeneration
- Nitric Oxide and Endothelin Effects
- Neurogenesis and neuroplasticity mechanisms
- Nerve Injury and Rehabilitation
- Neuroscience and Neuropharmacology Research
- Phosphodiesterase function and regulation
- Renin-Angiotensin System Studies
- Signaling Pathways in Disease
- Autism Spectrum Disorder Research
- Proteoglycans and glycosaminoglycans research
- Periodontal Regeneration and Treatments
- Neuroendocrine regulation and behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Conducting polymers and applications
- Muscle activation and electromyography studies
- Pain Mechanisms and Treatments
- Osteoarthritis Treatment and Mechanisms
- Immune Response and Inflammation
- Myofascial pain diagnosis and treatment
- Mesenchymal stem cell research
- Genetics and Neurodevelopmental Disorders
- RNA Interference and Gene Delivery
- Oxidative Organic Chemistry Reactions
- Receptor Mechanisms and Signaling
King's College London
2011-2022
Wolfson Foundation
2007-2017
University of Cambridge
2014
University College London
2006-2013
Sanskriti Samvardhan Mandal
2011
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...
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...
Brain function is usually perceived as being performed by neurons with the support of glial cells, network blood vessels situated nearby serving simply to provide nutrient and dispose metabolic waste. Revising this view, we find from experiments on a rodent central white matter tract (the optic nerve) in vitro that microvascular endothelial cells signal persistently axons using nitric oxide (NO) derived NO synthase (eNOS). The endogenous acts stimulate guanylyl cyclase-coupled receptors...
Nitric oxide (NO) functions as a diffusible transmitter in most tissues of the body and exerts its effects by binding to receptors harboring guanylyl cyclase transduction domain, resulting cGMP accumulation target cells. Despite widespread importance, very little is known about how this signaling pathway operates at physiological NO concentrations real time. To address these deficiencies, we have exploited properties novel biosensor, named δ-FlincG, expressed cells containing varying...
Abstract Chondroitin sulphate proteoglycans ( CSPG s) are extracellular matrix molecules whose inhibitory activity is attenuated by the enzyme chondroitinase ABC C h ). Here we assess whether degradation can promote compensatory sprouting of intact corticospinal tract CST ) following unilateral injury and restore function to denervated forelimb. Adult 57 BL /6 mice underwent pyramidotomy treatment with either or a vehicle control. Significant impairments in forepaw symmetry were observed...
Chondroitinase ABC (ChABC) has striking effects on promoting neuronal plasticity after spinal cord injury (SCI), but little is known about its involvement in other pathological mechanisms. Recent work showed that ChABC might also modulate the immune response by M2 macrophage polarization. Here we investigate detail immunoregulatory of SCI rats. Initially, examined expression profile 16 M1/M2 polarization markers at 3 h and 7 d postinjury. treatment had a clear effect signature SCI. More...
Following traumatic spinal cord injury, acute demyelination of axons is followed by a period spontaneous remyelination. However, this endogenous repair response suboptimal and may account for the persistently compromised function surviving axons. Spontaneous remyelination largely mediated Schwann cells, where demyelinated central axons, particularly in dorsal columns, become associated with peripheral myelin. The molecular control, functional role origin these remyelinating cells currently...
We recently discovered a novel role for neuregulin-1 (Nrg1) signaling in mediating spontaneous regenerative processes and functional repair after spinal cord injury (SCI). revealed that Nrg1 is the molecular signal responsible remyelination of dorsal column axons by peripheral nervous system (PNS)-like Schwann cells SCI. Here, we investigate whether Nrg1/ErbB controls unusual transformation centrally derived progenitor into these myelinating SCI using fate-mapping/lineage tracing approach....
In the hippocampus, as in many other CNS areas, nitric oxide (NO) participates synaptic plasticity, manifested changes pre- and/or postsynaptic function. While it is known that these are brought about by cGMP following activation of guanylyl cyclase-coupled NO receptors attempts to locate immunocytochemistry hippocampal slices response have failed detect elevation where expected, i.e. pyramidal neurones. Instead, astrocytes, unidentified varicose fibres and GABA-ergic nerve terminals...
Abstract Schwann cell grafts support axonal growth following spinal cord injury, but a boundary forms between the implanted cells and host astrocytes. Axons are reluctant to exit graft tissue in large part due surrounding inhibitory environment containing chondroitin sulphate proteoglycans (CSPGs). We use lentiviral chondroitinase ABC, capable of being secreted from mammalian (mChABC), examine repercussions CSPG digestion upon behaviour vitro. show that mChABC transduced robustly secrete...
Background and Purpose Isoform‐selective inhibitors of NOS enzymes are desirable as research tools for potential therapeutic purposes. V inyl‐l‐ N ‐5‐(1‐imino‐3‐butenyl)‐l‐ornithine ( l ‐ VNIO ) ω ‐propyl‐ ‐arginine NPA purportedly have good selectivity neuronal over endothelial under cell‐free conditions, does ‐[(3‐aminomethyl)benzyl]acetamidine 1400W ), which is primarily an inducible inhibitor. Although used in numerous investigations vitro vivo , there been surprisingly few tests the...
CDKL5 controls nociception in human neurons and murine models of deficiency disorder via CaMKII-dependent mechanisms.
Abstract Cervical level spinal cord injury (SCI) can severely impact upper limb muscle function, which is typically assessed in the clinic using electromyography (EMG). Here, we established novel preclinical methodology for EMG assessments of function after SCI awake freely moving animals. Adult female rats were implanted with recording electrodes bicep muscles and received bilateral cervical (C7) contusion injuries. Forelimb activity was by maximum voluntary contractions during a grip...
ABSTRACT Spinal cord injury (SCI) in mammals leads to irreversible tissue damage and loss of function. In contrast, axolotls are able regenerate scar-free the injured spinal cord. To explore new pathological mechanisms, we compared rat versus axolotl transcriptomics isolated genes shared between species post-SCI. Unexpectedly, multiple transcripts involved extracellular matrix remodelling, particular collagen-1, were upregulated both after SCI. Proteomics validated persistent expression...
Author order, and credits, on papers, seems to be one of those issues that won't go away.Each year more papers published in physiology -and the biosciences generally -have multiple (by which I mean than two) authors.As just small example, average number authors by J Physiol was 2.5 May 1987, 3.4 1997, 4.6 2007.So this shows there is research collaboration going on.That's good -right?Well, most universities these days have mission statements or like declaring their enthusiasm for...