[Rat model of HTLV-I infection--ultrastructural study of HAM rat disease]

HAM (HTLV-I-associated myelopathy) rat disease, HAM/TSP (HTLV-I-associated myelopathy/tropical spastic paraparesis)-like myelopathy in rats, occurred in 8 of 8 HTLV-I (Human T cell leukemia virus type I) carrier rats of WKAH strain inoculated with MT-2 cells at either neonates or 4 to 6 months of age. We report here ultrastructural findings of the affected spinal cords and the peripheral nerves of perfusion-fixed HAM rats. They were infected at the age of 4 to 6 months old and showed gait disturbance and hind leg paraparesis 15 months after infection. Pathological alterations of HAM rat disease were mainly confined to marginal areas of white matter of the spinal cord. The affected lesion was rather symmetrical and distributed in the anterior and the lateral columns. A prominent ultrastructural change in the spinal cord was separation of myelin lamellae at the intraperiod line and vacuolation of myelin sheath. Many myelin-debris-filled macrophages and a marked astrogliosis were also observed. In the gliotic areas, lots of demyelinated and remyelinated axons were intermingled. Axons were relatively preserved, however, some of them had tubulo-reticular inclusions. Astrocytes appeared ultrastructurally normal. Lymphocytic infiltration was virtually absent. Ultrastructural alterations of the peripheral nerve were basically similar to those of the spinal cord. Separation of myelin lamellae, macrophages infiltration, demyelination, and remyelination were observed. Schwann cells had also alterations. We observed some apoptotic cell death of the oligodendrocytes and Schwann cells with condensed nucleus and phagocytosis of apoptotic bodies by macrophages. Collective evidence suggests that a series of demyelinating process described above may be caused by apoptosis. No virus particles were seen in the spinal cord and peripheral nerve. Although the precise mechanism of apoptosis is not known at present, possible pathogenetic pathway involving apoptosis in HAM rat disease may contribute greatly to a better understanding of mechanisms implicated in the pathogenesis of HAM/TSP in humans.