Spinal cord lesions in spinal hyperostotic mouse (twy/twy) simulating ossification of the posterior longitudinal ligament of the cervical spine

Abstract

Introduction Application of compressive stress to the spinal cord may cause progressive compromise of its function and ultimately lead to the appearance of clinical symptoms such as myelopathy. Mechanical compression by Ossification of the posterior longitudinal ligament (OPLL) is a major cause of myelopathy [1], and further stress may result in serious damage to the neural tissue, including neuronal cell survival and axonal degeneration. From the aspects of therapeutics and neuroscience [2,3], it is essential to know the magnitude and extent of the stress due to OPLL that correlates with what degree of spinal cord dysfunction and tissue damage. A more important issue is to elucidate the biological and cytological behavior of spinal cord neurons under chronic mechanical compression. A spinal hyperostotic mouse model (twy/twy) that spontaneously develops calcifi cation and Ossification at the C1-C2 level, thereby severely compressing the spinal cord [4,5], has been used to study these issues. We have observed that brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 were essential for spinal cord motoneurons in vivo to survive mechanically injurious stimuli to the cord [6]. The neurotrophindefi cient condition after spinal cord injury results in sequela devastating to neuronal survival, including neuronal cell death. It has also been found that neurotrophin supplementation enhances neuronal survival [7]. Hypothesizing that neurotrophins help the mechanically compressed neurons survive in vivo, targeted retrograde administration of BDNF carrying recombinant adenovirus vector (AdV) was investigated experimentally. Here, we present an overview of spinal cord lesions in experimental animals that simulate human cervical OPLL myelopathy with respect to cytoarchitectonic behavior, immunohistological responses in wheat germ agglutinin (WGA)-horseradish peroxidase (HRP)-labeled neurons, expression of BDNF and NT-3 and their receptors (trkB, trkC), and the results of AdV-BDNF administration. © 2006 Springer.