Showing papers by "Gabriel Nistor published in 2007"

Therapeutic neutralization of CXCL10 decreases secondary degeneration and functional deficit after spinal cord injury in mice.

Abstract: Inflammation plays a critical role in the secondary degenerative response to spinal cord injury (SCI). The influx of inflammatory cells following SCI is preceded by the expression of specific chemoattractants, including chemokines. The chemokine CXCL10 is a potent T lymphocyte recruiter and has been strongly implicated in the pathology of many CNS disorders. We have previously demonstrated that CXCL10 exacerbates secondary degeneration by blocking the function of CXCL10 prior to SCI. Here we administered neutralizing antibodies against CXCL10 1 h after SCI in order to investigate the efficacy of this therapeutic intervention in abating histologic and functional deficit following acute SCI and further assess the functional role of CXCL10 in secondary degeneration. Neutralization of CXCL10 significantly reduced inflammation, apoptosis, neuronal loss and whole tissue loss. Notably, this therapeutic treatment also promoted revascularization of the injured spinal cord and functional recovery. These data suggest that anti-CXCL10 antibody treatment is a viable therapeutic strategy for acute SCI.

Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

Abstract: Chronic spinal cord injury (SCI) can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration. Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an Infinite Horizon Impactor. Animals were randomly distributed into 5 groups and killed 1 (n = 4), 28 (n = 4), 120 (n = 4), 450 (n = 5), or 540 (n = 5) days after injury. Morphometric and immunohistochemical studies were then performed on 1 mm block sections, 6 mm cranial and 6 mm caudal to the lesion epicenter. The SPSS 11.5 t test was used to determine differences between quantitative measures. Here, we document the first report of an ascending central canal dilation and progressive ependymal disruption cranial to the epicenter of injury in a contusion model of chronic SCI, which was characterized by extensive dural fibrosis and intraparenchymal cystic cavitation. Expansion of the central canal lumen beyond a critical diameter corresponded with ependymal cell ciliary loss, an empirically predictable thinning of the ependymal region, and a decrease in cell proliferation in the ependymal region. Large, aneurysmal dilations of the central canal were accompanied by disruptions in the ependymal layer, periependymal edema and gliosis, and destruction of the adjacent neuropil. Cells of the ependymal region play an important role in CSF homeostasis, cellular signaling and wound repair in the spinal cord. The possible effects of this ascending pathology on ependymal function are discussed. Our studies suggest central canal dilation and ependymal region disruption as steps in the pathogenesis of chronic SCI, identify central canal dilation as a marker of chronic SCI and provide novel targets for therapeutic intervention.

Oligodendrocyte Differentiation from Human Embryonic Stem Cells

Abstract: Publisher Summary Oligodendrocytes are glial cells that play a critical role in supporting the central nervous system (CNS). Specifically, they insulate axons and nerve cells within the CNS by wrapping them with myelin sheaths. The myelin sheath enables fast, saltatory conduction of impulses along the axons of neurons, controlling functions such as walking, perception of visual stimuli, and cognitive processes. When axons become demyelinated (i.e. lose their myelin sheath), as occurs in multiple sclerosis (MS) and spinal cord injury (SCI), axons cannot properly function. It may be due to loss and/or damage of oligodendrocytes. Therefore, replacement of oligodendrocytes or oligodendrocyte progenitor cells (OPCs) by cellular replacement therapies may in part restore axonal conduction and normal neuronal function. One approach to produce oligodendrocytes is through differentiation from embryonic stem cells (ESCs). This chapter describes an efficient way to produce OPCs from human embryonic stem cells (hESCs); specific examples are given for the WA01 and WA07 lines. Differentiation into oligodendroglial progenitors is attained by using specialized media supplemented with specific growth and differentiation factors at key time points. The resulting oligodendroglial progenitors are then amplified and positively selected using mechanical enrichment.