Leukocyte integrins as targets for neuroprotective strategies after spinal cord injury

Funding Details
Canadian Institutes of Health Research
  • Grant type: Operating Grant
  • Year: 2010/11
  • Total Funding: $117,935
Keywords
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Project Summary

Spinal cord injury (SCI) is a catastrophic event and a major health care issue, causing lifelong disability to its victims. In Canada ~1100 people suffer SCI annually, and ~36,000 live with permanent, serious disabilities due to SCI (Can. Paraplegic Assoc.). SCI happens to young people, usually in their 20¿s and changes their lives forever. The average direct healthcare cost is $1.25-$25 million during the life of each cord-injured person, generating a serious financial burden for the Canadian health care system and families of the victims. After SCI, entry of specific white blood cells (WBC) into the injured cord is a major contributor to intraspinal inflammation and secondary damage. Blocking this influx for about 3-4 days after SCI would greatly limit secondary damage. A therapy that does this selectively is urgently needed. We have shown that antibody (mAb)-mediated blockade of certain proteins (integrins) of WBC reduces their entry into the injured spinal cord of rats, greatly improving neurological outcomes and tissue integrity. The proposed research will compare effects of mAb-blockade of two different integrins: our previously studied CD11d/CD18 integrin and a similar one, a4B1. We will determine if a mAb to a4B1 blocks the entry of WBC into the injured cord, averting their damaging effects. We will compare the protection of the injured cord afforded by blocking these two different integrins and will investigate mechanisms by which they contribute to cord damage. mAb that block the integrins on WBC might be suitable for clinical treatment of SCI but first we must understand how they work.