Search our Database of Scientific Publications and Authors

I’m looking for a

    Details and Download Full Text PDF:
    An integrin inhibiting molecule decreases oxidative damage and improves neurological function after spinal cord injury.

    Exp Neurol 2008 Dec 26;214(2):160-7. Epub 2008 Sep 26.
    Spinal Cord Injury Laboratory, BioTherapeutics Research Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario, PO Box 5015, 100 Perth Drive, London, Ontario Canada.
    Our previous studies have shown that treatment with an alpha4beta1 integrin blocking antibody after spinal cord injury (SCI) in rats decreases intraspinal inflammation and oxidative damage, improving neurological function. Here, we studied effects of a high affinity small molecule alpha4beta1 inhibitor, BIO5192. First, rats were treated intravenously with BIO5192 (10 mg/kg) or with vehicle (controls) to assess effects of integrin blockade for 24 h or 72 h after thoracic clip-compression SCI. BIO5192 treatment significantly decreased the MPO enzymatic activity (neutrophil infiltration) and ED-1 expression (macrophage density) by 40% and 38% at 24 h and by 52% and 25% at 72 h post injury, respectively. In cord homogenates, BIO5192 treatment decreased expression of the oxidative enzymes gp91(phox), inducible nitric oxide and cyclooxygenase-2 by approximately 40% at both times of analysis. Free radical concentration decreased by 30% and lipid peroxidation decreased by 34% and 46%, respectively, at 24 h and 72 h after SCI. Next, after blockade by BIO5192 for 72 h, neurological outcomes were analyzed for 1-6 weeks after SCI. Motor function significantly improved when assessed by an open-field test. Treated rats planter placed their hind paws and/or dorsal stepped, with weight support, whereas controls only swept their hindlimbs. BIO5192 treatment also decreased mechanical allodynia elicited from the trunk and hind paw by up to 35%. This improved function correlated with decreased lesion size and spared myelin-containing white matter. The neurological improvement offered by this neuroprotective strategy supports the potential for an anti-integrin treatment for SCI.
    PDF Download - Full Text Link
    ( Please be advised that this article is hosted on an external website not affiliated with
    Source Status ListingPossible

    Similar Publications

    Alpha4beta1 integrin blockade after spinal cord injury decreases damage and improves neurological function.
    Exp Neurol 2008 Dec 1;214(2):147-59. Epub 2008 May 1.
    Spinal Cord Injury Laboratory, BioTherapeutics Research Group, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada N6A 5K8.
    The extent of disability caused by spinal cord injury (SCI) relates to secondary tissue destruction arising partly from an intraspinal influx of neutrophils and monocyte/macrophages after the initial injury. The integrin alpha4beta1, expressed by these leukocytes, is a key to their activation and migration into/within tissue. Therefore, blocking this integrin's functions may afford significant neuroprotection. Read More
    Timing and duration of anti-alpha4beta1 integrin treatment after spinal cord injury: effect on therapeutic efficacy.
    J Neurosurg Spine 2009 Nov;11(5):575-87
    Spinal Cord Injury Laboratory, The University of Western Ontario, London, Ontario, Canada.
    Object: After spinal cord injury (SCI) leukocytes infiltrate the injured cord, causing significant damage and further impairment of functional recovery. The leukocyte integrin alpha4beta1 is crucial for their entry. The authors previously demonstrated that an anti-alpha4 monoclonal antibody (mAb) treatment attenuates leukocyte infiltration, improves motor and autonomic function, and reduces neuropathic pain when administered at 2 hours and 24 hours after SCI. Read More
    Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats.
    J Neurochem 2004 Mar;88(6):1335-44
    Spinal Cord Injury Team, BioTherapeutics Research Group, Robarts Research Institute, London, Ontario, Canada.
    We investigated mechanisms by which a monoclonal antibody (mAb) against the CD11d subunit of the leukocyte integrin CD11d/CD18 improves neurological recovery after spinal cord injury (SCI) in the rat. The effects of an anti-CD11d mAb treatment were assessed on ED-1 expression (estimating macrophage infiltration), myeloperoxidase activity (MPO, approximating neutrophil infiltration), lipid peroxidation, inducible nitric oxide synthase (iNOS) and nitrotyrosine (indicating protein nitration) expression in the spinal cord lesion after severe clip-compression injury. Protein expression was evaluated by western blotting and immunocytochemistry. Read More
    The tripeptide phenylalanine-(D) glutamate-(D) glycine modulates leukocyte infiltration and oxidative damage in rat injured spinal cord.
    Neuroscience 2006 Jul 3;140(3):1011-22. Epub 2006 Apr 3.
    Spinal Cord Injury Team, Laboratory of Spinal Cord Injury, BioTherapeutics Research Group, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada N6A 5K8.
    The tripeptide, phenylalanine-glutamate-glycine (FEG) and its d-isomeric form phenylalanine-(D) glutamate-(D) glycine (feG), derived from submandibular gland peptide-T, significantly reduce the allergic inflammatory response and leukocyte trafficking and neutrophil migration into intestine, heart and lungs. Due to these actions, we hypothesized that feG would attenuate the early inflammatory response to spinal cord injury, reduce free radical production and improve neurological outcomes, like other leukocyte-limiting strategies we have used previously. We tested this using a clip compression model of spinal cord injury in rats. Read More