Kyokazu Ono

Development of corticospinal tract fibers and their plasticity I: Quantitative analysis of the developing corticospinal tract in mice

This study was undertaken to elucidate ultrastructurally and quantitatively the development of the corticospinal tract (CST) axons of mouse at the intumescence level of the cervical cord. An anterograde HRP study showed that the CST was located at the ventral one-third of the dorsal funiculus, and a few HRP-positive fibers were noted at the medialmost part of the ipsilateral anterior funiculus. Ultrastructurally, the CST was composed of unmyelinated axons, growth cones and a few degenerating axons until postnatal day 10 (P10), then the axons in CST gradually increased in size. The number of axons constituting the right CST was calculated at different days of age. The total numbers of axons at P0, P4, P14, P21 and P56 were 2.3 x 10(4), 6.2 x 10(4), 10.4 x 10(4), 7.1 x 10(4) and 3.5 x 10(4), respectively. These results indicate that the number of CST axons at the cervical intumescence of mouse becomes maximum at P14, and then decreases rapidly to reach the adult level of 3.5 x 10(4) (at P56), about 68% of them thus being lost.

Reorganization of the corticospinal tract following neonatal unilateral cortical ablation in rats.

The corticospinal tract in the rat after neonatal ablation of the unilateral cerebral cortex was studied morphologically and histochemically using the retrograde and antegrade horseradish peroxidase (HRP) tracing methods. The normal corticospinal tract in the lumbar cord was composed of a number of small and some large axons. In the atrophic corticospinal tract related to the ablated cerebral cortex, the small axons were decreased in number two weeks after the operation. However, new myelinated small axons appeared around day 28 and their diameters increased gradually from after day 56 to day 84. The original large axon in the atrophic corticospinal tract was much more increased in size than that in the corticospinal tract of the non-operated-on control. When HRP was injected into the left cervical cord of the adult rat whose right cerebral cortex had been ablated during the neonatal period, a considerable number of HRP-labeled neurons was seen in the healthy left cerebral cortex. When the corticospinal tract was traced antegradely by injecting HRP into the healthy left cerebral cortex, an aberrant corticospinal tract reaching into the ipsilateral dorsal funiculus was observed. These results give a morphological basis for the well known fact that children who have had brain damage during the neonatal period and early infancy have the capacity for recovery of motor function.

Development of corticospinal tract fibers and their plasticity II. Neonatal unilateral cortical damage and subsequent development of the corticospinal tract in mice

In this study, the right cerebral cortices of mice on postnatal day 0 (P0) were cryocoagulated with dry ice. Subsequent development of the corticospinal tract (CST) was studied morphologically and quantitatively, and was compared with that in age-matched controls. When the pyramidal tract was traced anterogradely by injecting HRP into the sensorimotor area of the left cerebral cortex of adult operated mice, the right CST originating from the healthy left hemisphere showed remarkable hypertrophy. The number of axons in the CST at the C4-C6 level became maximum on P14 in the control mice and rapidly decreased thereafter. In the operated mice, the axonal number in the right CST also was maximal on P14 and then rapidly decreased. However, the decrease in axonal number after P21 was less in the operated mice than in the controls. Moreover, the number of axons showed a slight increase after P56. These results indicate that the physiological elimination of the parent axons and their collaterals is much lower in the operated mice than in the controls, and that the increase in axon collaterals from parent axons in the hypertrophic right CST persists a long time in the operated mice.

Formation of an ipsilateral corticospinal tract after ablation of cerebral cortex in neonatal rat

The formation of an aberrant ipsilateral corticospinal tract after unilateral cerebral cortical ablation during the neonatal period has been confirmed in the rat. The tract was chronologically studied using the antegrade horseradish peroxidase (HRP) tracing method. An aberrant ipsilateral tract is not observed 3 days after the operation. However, ipsilateral HRP positive fibers become apparent on day 7 and progressively more prominent until day 14. These results suggest that the ipsilateral corticospinal tract is composed of collateral axons originating from pyramidal neurons in the healthy ipsilateral cerebral cortex. These results also indicate that, when cerebral cortex has the damage during early postnatal life, the remaining cortical neurons which have been freed from the damage show considerable plasticity in terms of the collateral axons.

Electron microscopic study on brain of macular mutant mouse after copper therapy

SummaryThe hemizygote of the macular mutant mice, which is clinically and neuropathologically considered to be a model of Menkes kinky hair disease (MKHD), were injected intraperitoneally four times with 10, 20, 20 and 30 μg of cupric chloride on days 4, 6, 8 and 10 after birth, respectively. Their cerebral and cerebellar cortices were chronologically examined by electron microscopy. In the cerebral cortes, only a few abnormal mitochondria with electron-lucent matrix and short peripherally located cristae were scattered in the neurons on day 14, and these had almost entirely vanished after day 21. In the cerebellar cortex, abnormal mitochondria were frequently found on day 14 in the dendrites of the Purkinje cells, whereas they were only occasionally observed in their cytoplasm. Those in the dendrites had decreased in number on day 30, and only a few of them were seen in the cerebellum after day 45. These results show that the copper therapy reduced ultrastructural abnormalities in the hemizygote of this mutant mouse.

Axon ramification following unilateral cortical ablation in neonatal rats.

We confirmed the formation of an aberrant ipsilateral corticospinal tract after unilateral cerebral cortical ablation during the neonatal period in rat. This tract was studied using anterograde horseradish peroxidase (HRP) tracing. Ramifications of the axons in the pyramidal tract were found to contribute to the ipsilateral tract at the level of the pyramidal decussation, suggesting that ramification of immature axons play an important role in the formation of the ipsilateral corticospinal tract.