ASTROCYTES AFFECT THE SYMPTOMS OF MULTIPLE SCLEROSIS

因为已知脱髓鞘的中央轴突和星形胶质细胞

Since demyelinated central axons and astrocytes are known to interact intimately and specifically with each other, it is pertinent to question whether astrocyte-free demyelinated axons may have different physiological properties from their astrocyte ensheathed counterparts. The physiological properties of astrocyte-free demyelinated axons are not known. The hypothesis to be tested is that the presence or absence of an astroglial covering along a demyelinated internode may affect the presence or absence of conduction through the lesion, and the presence or absence or spurious nervous impulses generated ectopically at the lesion. The findings will be of relevant to multiple sclerosis since the MS lesion contains many astrocytes-free demyelinated axons, especially at the center of the larger lesions. A combination of physiological and morphological protocols will be applied to the examination of two types of central demyelinating lesion. In one lesion, the demyelinated axons remain entirely free of astroglial contacts for many months, whereas in the other, the axons are individually ensheathed by astrocytes. The physiological examination will use both acutely prepared, and chronically implanted preparations to determine the conduction properties of the axons, including the presence or absence of conduction through the lesion; the security of conduction where present; the ability of the fibers to conduct long, high frequency trains of impulses; the presence or absence of ectopically-generated action potentials: and the effects on the conductive properties of certain pharmacological agents advanced as being of potential or a benefit to patients with MS. The morphological examination will employ affinity purified antibodies (raised against isolated rat CNS sodium channel) to reveal the sodium channel distribution along the demyelinated axons, and to compare this distribution with that of the astrocytes, when present. The physiological properties described are believed to underlie the negative symptoms (e.g. paralysis and blindness) and the positive symptoms (e.g. tingling paraesthesia), of MS. It seems quite possible that the effectiveness of the astrocytic response may determine, at least in part, the presence or absence of remissions from the symptoms. Certainly in is not unreasonable to hope that a greater understanding of the role of neuro-glial cells in pathological processes and repair may lead to new approaches in the symptomatic therapy of multiple sclerosis and related disorders.