Complement inhibition attenuates brain edema and neurological deficits induced by thrombin.

Abstract

The present study examined whether thrombin activates the complement cascade in the brain and whether N-acetylheparin, an inhibitor of complement activation, attenuates brain injury induced by thrombin. There were three sets of studies. In the first set, rats had an intracerebral infusion of either five-unit thrombin or a needle insertion. Brains were sampled at 24 hours for Western blot analysis and immuno-histochemistry. In the second set, rats received either five-unit thrombin+saline, five-unit thrombin+25 microg N-acetylheparin or five-unit thrombin+100 microg N-acetylheparin infusion. Brains were sampled 24 hours later for water content measurement. In the third set, rats received either five-unit thrombin+saline or five-unit thrombin+ 100 microg N-acetylheparin. Behavioral tests sensitive to unilateral striatal damage were carried out for two weeks. Western blotting demonstrated that complement C9 and clusterin levels increase 24 hours after thrombin infusion (P < 0.01). Both C9 and clusterin positive cells were found around the injection site. High-dose (100-microg) but not low-dose (25-microg) N-acetylheparin attenuated thrombin-induced brain edema (81.5 +/- 0.4% vs. 83.7 +/- 0.3% in the vehicle, P < 0.05). Behavior was also significantly improved by N-acetylheparin (P < 0.05). In conclusion, thrombin-induced edema formation and neurological deficits were both reduced by N-acetylheparin. This suggests that inhibition may be a novel treatment for the thrombin-induced brain injury that occurs in intracerebral hemorrhage.

• Authors: Y Gong, G H Xi, R F Keep, J T Hoff, Y Hua
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 95 Pg. 389-92 ( 2005) ISSN: 0065-1419 [Print] Austria
• PMID: 16463887 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Complement Inactivating Agents
• Drug Combinations
• N-acetylheparin
• Heparin
• Thrombin

Topics

• Animals
• Behavior, Animal (drug effects)
• Brain Edema (chemically induced, immunology, prevention & control)
• Complement Activation (drug effects, immunology)
• Complement Inactivating Agents (administration & dosage)
• Dose-Response Relationship, Drug
• Drug Combinations
• Heparin (administration & dosage, analogs & derivatives)
• Male
• Nervous System Diseases (chemically induced, immunology, prevention & control)
• Rats
• Rats, Sprague-Dawley
• Thrombin (adverse effects)
• Treatment Outcome