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.
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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. Read More
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
J Neurosci 2004 Apr;24(16):4043-51
Spinal Cord Injury Team, BioTherapeutics Research Group, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 5K8, Canada.
The early inflammatory response to spinal cord injury (SCI) causes significant secondary damage. Strategies that nonselectively suppress inflammation have not improved outcomes after SCI, perhaps because inflammation has both adverse and beneficial effects after SCI. We have shown that the selective, time-limited action of a monoclonal antibody (mAb) to the CD11d subunit of the CD11d/CD18 integrin, delivered intravenously during the first 48 hr after SCI in rats, markedly decreases the infiltration of neutrophils and delays the entry of hematogenous monocyte-macrophages into the injured cord. Read More
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