Journal article
Interleukin-1 Receptor Antagonist Attenuates Regional Neuronal Cell Death and Cognitive Dysfunction after Experimental Brain Injury
Journal of cerebral blood flow and metabolism, v 19(10), pp 1118-1125
Oct 1999
PMID: 10532636
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The effect of systemic administration of human recombinant interleukin-1 receptor antagonist (rhIL-1ra) on behavioral outcome and histopathologic damage after lateral fluid-percussion brain injury of moderate severity was evaluated. In study 1, brain-injured Sprague Dawley rats received timed subcutaneous injections beginning 15 minutes after injury of either 100 mg/kg rhIL-1ra (high dose, total dose = 1900 mg/kg), 10 mg/kg rhIL-1ra (low dose, total dose = 190 mg/kg), or vehicle over 7 days. No effect of low-dose rhIL-1ra was observed in study 1. High-dose rhIL-1ra significantly attenuated posttraumatic neuronal loss in the injured hippocampal CA3 region (P < 0.05), dentate hilus (P < 0.05), and cortex (P < 0.05) but impaired recovery of motor function at 7 days after trauma (P < 0.05). In study 2, rats were pretrained to learn a visuospatial task in a Morris water maze, subjected to fluid-percussion brain injury or sham treatment, and randomly assigned to receive multiple subcutaneous injections at timed intervals of 100 mg/kg rhIL-1ra (total dose = 900 mg/kg) or vehicle over 42 hours, followed by continuous infusion of a lower concentration of rhIL-1ra (20 mg/kg/day, total dose = 100 mg/kg), or vehicle for 5 days using subcutaneously implanted osmotic minipumps. Postinjury administration of rhIL-1ra significantly attenuated cognitive deficits compared with vehicle-treated animals at 42 hours (P < 0.05) but did not affect motor function at 48 hours, 1 week, and 2 weeks. These results suggest that inhibitors of cytokine pathways may be therapeutically useful for the treatment of brain trauma.
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Details
- Title
- Interleukin-1 Receptor Antagonist Attenuates Regional Neuronal Cell Death and Cognitive Dysfunction after Experimental Brain Injury
- Creators
- Kristin L Sanderson - Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.ARamesh Raghupathi - Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.AKathryn E Saatman - Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.ADavid Martin - Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.AGerald Miller - Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.ATracy K McIntosh - Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A
- Publication Details
- Journal of cerebral blood flow and metabolism, v 19(10), pp 1118-1125
- Publisher
- SAGE Publications; London, England
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000084883900008
- Scopus ID
- 2-s2.0-0033505017
- Other Identifier
- 991014878311204721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism
- Hematology
- Neurosciences