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We examined the structural changes of capillaries in the extensor digitorum longus muscle of aged (25 months) male BUF/Mna rats, which caused severe muscle weakness of hind legs during aging. The aged muscle mostly consisted of bundles of muscle fibres 15-35 µm in diameter (type 1). In some small areas, however, muscle bundles contained small muscle fibres mainly 15-25 µm in diameter (type 2), possibly indicating that these small fibres are in the course of regeneration after necrosis. Examination of serial ultrathin sections revealed some remarkable changes of capillaries in the type 2 muscle bundle. In some capillaries, the vascular lumen became discontinuous by several close contacts of opposed endothelial cells in their course, forming plural closed vascular segments. Moreover, a solitary endothelial cell was often observed within a scaffold of basal lamina, which remained after destruction of endothelial cells. The segmentation of capillaries and the occurrence of the scaffolds of basal laminae are considered to indicate the degenerative process of capillaries. In some instances, on the other hand, endothelial cells closely apposed each other with no vascular lumen for distances of up to 100 µm, and some capillaries had a narrow vascular lumen (1-3 µm diameter) for a long distance (∼300 µm), probably indicating that these structures are in the course of regenerating capillaries to remodel the capillary networks around the muscle fibres. Pericytic processes circularly arranged outside the endothelium at the slit-like and narrow vascular lumen, like hoops, possibly preventing the rupture of the newly-formed vascular lumen from the increased blood flow and/or blood pressure. In addition, the occasional occurrence of capillaries with fenestrations may participate to increase the supply of nutrients and oxygen to the regenerating muscle fibres. The present findings suggest that the capillary networks in the extensor digitorum longus muscle of aged BUF/Mna rats are remodelled following the regeneration of muscle fibres after necrosis, and that on occasion, neighbouring endothelial cells may closely contact with each other both in the degenerative and regenerative processes of capillaries.

Structural changes of capillaries around muscle fibres following their degeneration and regeneration were further examined in the extensor digitorum longus muscle of the 24-month-old normal rat. Bundles of muscle fibres were divided into three types: muscle bundles consisting of large muscle fibres exclusively more than 35 µm in diameter (type 1), various-sized muscle fibres ranging from 10 to 60 µm in diameter (type 2) and only small muscle fibres 20-40 µm in diameter (type 3). The mean number of capillaries around a muscle fibre was extremely high in the type 3 muscle bundle (4.83) and much lower in the type 2 muscle bundle (2.72) compared with that in the type 1 muscle bundle (3.48). Capillaries in the type 1 muscle bundle were round or oval in shape and were of the continuous type. In the type 2 muscle bundle, capillaries around large degenerating muscle fibres showed an irregularly compressed shape and the scaffolds of basal laminae were often found around them, being a result of the destruction of capillaries. On the other hand, small-sized capillaries less than 5 µm in diameter, being possibly regenerating capillaries, were found around small (probably regenerating) muscle fibres and often had a small number (less than 10) of fenestrae. Capillaries in the type 3 muscle bundle, similar in shape and size to those in the type 1, frequently branched or joined, but some of them were partially destroyed. These findings suggest that capillaries degenerate and regenerate to remodel capillary networks around the muscle fibres following their degeneration and regeneration, and that to effectively supply oxygen and nutrients to regenerating muscle fibres, capillaries temporarily form fenestrae and then the capillary networks become dense by sprouts from the existing capillaries, but excess capillaries may be gradually destroyed following maturation of the muscle fibres.

The outer capsule, inner capsule and fusimotor endings of muscle spindles in the tenuissimus muscle of mature Chinese hamsters were examined by scanning electron microscopy (SEM). The thin and long tenuissimus muscle was transversely cut into several segments, and the segments were longitudinally or obliquely cut with a razor blade to mechanically remove the spindle sheath (outer capsule). These specimens were treated with 8 N HCl at 60°C to isolate the muscle spindles and clearly expose the internal structures such as the inner capsule and fusimotor endings innervating intrafusal muscle fibers. The spindle sheath was about 1 mm long and at the equator about 50 µm in diameter. Within the outer capsule, cells of the inner capsule in the equatorial region were polygonal in shape, and continuously surrounded the axial bundle like a sleeve. This continuous sheath became sieve-like in the juxta-equatorial region, depending on the twining of thin and flattened cytoplasmic extensions and/or processes of the cells. Owing to the continuous inner capsular sheath in the equatorial region, the arrangement of sensory endings were not visualized under SEM. Fusimotor endings observed in the juxta-equatorial and polar regions consisted of poorly-developed subneural apparatuses with predominantly pit-like and short slit-like junctional folds.

Abstract: BUF/Mna rats spontaneously develop thymomas and cause muscle weakness of hind legs at an advanced age. This rat strain has been recognized as a suitable animal model for human myasthenia gravis or related myopathies. To characterize the structural changes of neuromuscular junctions (NMJs) in BUF/Mna rats, subneural apparatuses (SNAs) of extensor digitorum longus muscles of young-adult (4-month-old) and aged (22- to 25-month-old) male rats were examined using scanning and transmission electron microscopy. The SNAs of NMJs in young rats consist of complex labyrinthine gutters with numerous slit-like junctional folds. SNAs in aged BUF/Mna rats, however, are characterized by: (1) a group of cup-like depressions with very wide slit-like junctional folds in relatively large muscle fibers (the major type), (2) the presence of slit-like folds on the flat sarcoplasm outside the cup-like depressions or on the protruded sarcoplasm, and (3) winding gutters or a small number of round depressions with poorly developed synaptic folds in small and medium-sized muscle fibers (the minor type). Since similar structural changes have been reported in dystrophic mice or normally aged rats, it is suggested that both the slowly progressing muscle atrophy and age-dependent turnover of muscle fibers may occur in the aged BUF/Mna rats.