Neurologic and Histologic Tests Used to Measure Neuroprotective Effectiveness of Virus-Derived Immune-Modulating Proteins

Jacek M. Kwiecien, Jordan Yaron, Kathleen H. Delaney, Alexandra R. Lucas

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Severe inflammatory disease initiated by neurotrauma and stroke is of primary concern in these intractable pathologies as noted in recent studies and understanding of the pathogenesis of spinal cord injury (SCI) in the rat model. Successful anti-inflammatory treatments should result in neuroprotection and limit the loss of neurological function to injury caused by the initial damage. Continuous subdural infusion offers direct access to the cavity of injury (COI) that forms after balloon crush SCI deep in the spinal cord. Some anti-inflammatory compounds are not likely capable of crossing the blood-spinal cord barrier. Subdural infusion of myxoma virus-derived Serp-1, an anti-thrombotic/anti-thrombolytic, and also of M-T7, a chemokine inhibitor, improved the locomotor scores and pain sensation scores as well as reduced the numbers of macrophages in the COI by 50 and 80%, respectively, while intraperitoneal infusion of either protein had little effect. Injection of a chitosan hydrogel loaded with Serp-1 into the dorsal spinal column crush also resulted in improved neurological deficits and in reduction of the size of the crush lesion 4 weeks after injury. While neurological scores in a simplified hind-end (HE) locomotor test together with a toe-pinch withdrawal test demonstrated improvement in all balloon crush injury and dorsal spinal crush injury rats, a severe inflammation is induced by the injury indicating additional damage to the spinal cord. Thus neurological function testing can be contradictory, rather than corresponding, to the pathogenesis of SCI. The count of macrophages in the COI offers a precise, reliable method of measuring the effectiveness of a neuroprotective treatment of SCI in preclinical studies.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages227-239
Number of pages13
DOIs
StatePublished - 2021

Publication series

NameMethods in Molecular Biology
Volume2225
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Anti-inflammatory treatment
  • Cavity of injury
  • M-T7
  • Macrophage quantification
  • Neuroinflammation
  • Neuroprotection
  • Serp-1
  • Spinal cord implantation
  • Spinal cord injury
  • Subdural infusion

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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