Inflammatory response of the spinal cord to multiple episodes of blood-brain barrier disruption and toxic demyelination in Wistar rats

Abstract

Multiple episodes of blood-brain barrier disruption were induced by sequential intraspinal injections of ethidium bromide. In addition to the barrier disruption, there was toxic demyelination and exposure of myelin components to the immune system. Twenty-seven 3-monthold Wistar rats received 2, 3 or 4 injections of 1 µl of either 0.1% ethidium bromide in normal saline (19 rats) or 0.9% saline (8 rats) at different levels of the spinal cord. The time intervals between the injections ranged from 28 to 42 days. Ten days after the last injection, all rats were perfused with 2.5% glutaraldehyde. The spinal sections were evaluated macroscopically and by light and transmission electron microscopy. All the lesions demonstrated a mononuclear phagocytic infiltrate apparently removing myelin. Lymphocytes were not conspicuous and were found in only 34% of the lesions. No perivascular cuffings were detected. In older lesions (38 days and older) they were found only within Virchow-Robin spaces. This result suggests that multiple blood-brain barrier disruptions with demyelination and exposure of myelin components to the immune system were not sufficient to induce an immune-mediated reaction in the central nervous system.

Behaviour of oligodendrocytes and Schwann cells in an experimental model of toxic demyelination of the central nervous system

“…They were interpreted as part of the general inflammatory influx induced by the chemical 11 .Those experiments using multiple injections in the spinal cord 23 confirmed the suspicion that there is no immune interference in the EB lesions. The presence of lymphocytes in the early stages of demyelination addresses these cells as a component of the whole inflammatory response that have a brief interaction with macrophages who might be the actual effector cells within the CNS 24 .…”

Probing the influence of myelin and glia on the tensile properties of the spinal cord

“…Both techniques are wellaccepted and commonly used to demyelinate tissue, primarily in models of multiple sclerosis (MS) as well as to evaluate the natural time course of and therapeutic approaches for remyelination (Graca and Blakemore 1986;Fernandes et al 1998;Pereira et al 1998). EB is a DNA-intercalating dye that is cytotoxic to dividing cells, which disrupts the glial matrix by selectively killing astrocytes and oligodendrocytes, and can also disrupt the blood-brain barrier, while preserving neurons (Fernandes et al 1998;Pereira et al 1998). While no reports of the use of EB in chick embryo models were found, our results were consistent with those found in other species, where demyelination is observed with a few days of injection.…”