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Antibodies to Dynorphin A (1-17) Attenuate Closed Head Injury Induced Blood-Brain Barrier Disruption, Brain Edema Formation and Brain Pathology in the Rat
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
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2010 (English)In: Brain Edema XIV / [ed] Zbigniew Czernicki et al., Vienna: Springer , 2010, Vol. 106, 301-306 p.Conference paper, Published paper (Refereed)
Abstract [en]

The potential neuroprotective efficacy of dynorphin A antiserum on BBB dysfunction, edema formation and brain pathology was examined in a closed head injury (CHI) model in the rat. The CHI was produced by an impact of 0.224 N on the right parietal bone under anesthesia by dropping a weight of 114.6 g on the skull from a height of 20 cm through a guide tube. This concussive brain injury resulted in profound BBB disruption as evidenced by leakage of Evans blue and radioiodine in the brain. Edema formation and swelling at 5 h were most pronounced in the contralateral cerebral hemisphere. Pretreatment with dynorphin A antiserum (1:20, monoclonal) infused into the left lateral cerebral ventricle (30 mu L in PBS) either 30 min before or 30 min after CHI significantly attenuated BBB dysfunction, brain edema formation, volume swelling and brain pathology. However, no reduction in brain edema, BBB permeability or improved brain pathology was seen when the antiserum was given 60 min post-CHI. These observations are the first to suggest that antiserum to dynorphin when administered into the CSF during early phase of CHI is neuroprotective. Our work further indicates that dynorphin is actively involved in the cellular and molecular mechanisms of edema formation and BBB breakdown in CHI.

Place, publisher, year, edition, pages
Vienna: Springer , 2010. Vol. 106, 301-306 p.
Series
Acta Neurochirurgica Supplementum, ISSN 0065-1419 ; 106/8
Keyword [en]
Closed head injury, dynorphin A antiserum, blood-brain barrier, brain edema, brain pathology
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-137492DOI: 10.1007/978-3-211-98811-4_56ISI: 000274867500056ISBN: 978-3-211-98758-2 (print)ISBN: 978-3-211-98811-4 (print)OAI: oai:DiVA.org:uu-137492DiVA: diva2:378300
Conference
14th International Symposium on Brain Edema and Brain Tissue Injury Warsaw, POLAND, JUN 11-14, 2008
Available from: 2010-12-15 Created: 2010-12-15 Last updated: 2012-03-15Bibliographically approved

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Sharma, Hari Shanker

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