Neuroprotective effects of the novel polyethylene glycol-hemoglobin conjugate SB1 on experimental cerebral thromboembolism in rats

Eur J Pharmacol. 2007 Jul 2;566(1-3):83-7. doi: 10.1016/j.ejphar.2007.02.061. Epub 2007 Mar 12.

Abstract

SunBio1 (SB1) is a novel polyethylene glycol-bovine hemoglobin conjugate. It is a small molecule that shows high oxygen-delivery capacity, and exhibits extended plasma half-life compared to hemoglobin alone, thus reducing renal toxicity. The aim of the present study was to evaluate potential neuroprotective effects of SB1 using a rat middle cerebral artery occlusion model. The middle cerebral artery of male Sprague-Dawley rats was occluded with a thrombotic blood clot and SB1 was administered via intra-arterial infusion 5 min after the operation. Brain tissue was harvested after 2 h, and cerebral infarct volumes were calculated from coronal sections stained with 2,3,5-triphenyltetrazolium chloride. Three to 6 days after the procedure, sub-groups of animals were subjected to an open field test and the Morris water maze to assess locomotor activity and learning/memory function. Thrombotic blood clots induced extensive brain infarction and edema; however, these were significantly reduced in SB1 treated animals. In addition, SB1 treatment increased locomotor activity in open field tests, and improved the learning/memory deficits caused by the thromboembolism. These results suggest that SB1 has neuroprotective effects against ischemic brain injury caused by thromboembolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Occlusive Diseases / drug therapy*
  • Arterial Occlusive Diseases / pathology
  • Arterial Occlusive Diseases / physiopathology
  • Behavior, Animal / drug effects
  • Hemoglobins / pharmacology*
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Intracranial Thrombosis / drug therapy*
  • Intracranial Thrombosis / pathology
  • Intracranial Thrombosis / physiopathology
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Polyethylene Glycols / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Hemoglobins
  • Neuroprotective Agents
  • PEG-hemoglobin
  • Polyethylene Glycols