Nerve fiber injury and endoneurial edema were induced by the injection of the local anesthetic 2-chloroprocaine, tetracaine, procaine, etidocaine or mepivacaine into the soft tissue and fascia surrounding the sciatic nerve of Sprague-Dawley rats. Light microscopy demonstrated that the perineurial barrier was not mechanically damaged by the surgical procedure but, at 48 h post-injection, perineurial permeability was increased. Previous observations of leakage of horseradish peroxidase and the present report of neutrophils and eosinophils in the endoneurium indicate a disruption of blood-nerve barrier systems. Endoneurial edema was observed in the subperineurial, interstitial and perivascular regions. Axonal degeneration and demyelination occurred; the latter associated with accumulation of large lipid droplets in Schwann cells. Degranulation of mast cells, proliferation of fibroblasts and macrophage activity were noteworthy in affected areas. The findings are remarkable in that this is the first model of endoneurial edema by a neurotoxin which penetrates the perineurium, disrupting barrier system and inducing nerve fiber injury.

Pathology of local anesthetic-induced nerve injury.

The ultrastructural alterations in oligodendrocytes in the zitter rat — a newly established animal model of CNS hypomyelination — were studied in animals between 3 and 37 weeks of age. Throughout the observation period, the most characteristic alteration was the presence of abnormal structures associated with nuclear membranes and resembling split myelin lamellae. The structures consisted of stacks of membranes continuous with the inner and outer membranes of the nuclear envelope or with plasma membranes. This abnormality was prominent at 3 weeks of age, when initial myelination was probably still occurring. It was decreased transiently at 12 weeks of age and then again increased slightly with advancing age. However, the mean incidence of this abnormality was approximately 5% of the oligodendrocyte nuclei in randomly examined electron micrographs. As the small membranous abnormalities were observed in a few serial sections, the actual incidence is believed to be several times higher than 5%. Such membranous abnormalities were also detected in some mitochondria, in some cisternae of rough endoplasmic reticulum, and in some lysosomes, all at lower incidence rates. Some aberrant or elongated myelin sheath formations, an increased number of radial components and intracytoplasmic inclusions in oligodendrocytes were also observed. These findings suggest that functional abnormalities in membrane biosynthesis including the myelin sheaths and the nuclear membranes in oligodendrocytes are closely related to the hypomyelination in the CNS and may be related to the genetic abnormality in the zitter rat.

An ultrastructural study of oligodendrocytes in zitter rat: a new animal model for hypomyelination in the CNS.

In the oligodendrocytes of cerebellum and spinal cord and in the Schwann cells of peripheral nerves of cat, albino mouse, and Japanese waltzing mouse lipopigment bodies of different size and shape are deposited, which exhibit a characteristic internal structure. The following three subtypes can be distinguished: (1) Granules completely surrounded by a membrane and containing regularly speced lamellae, (2) granules consisting of a granular matrix with elucidations, and (3) granules with bifurcating stacks of lamellae. Thus, their structure is distinct from that found in nerve cells and other glial cells and allows the diagnosis of oligodendrocyte or Schwann cell. The significance of these granules in relation to function and aging is briefly discussed.

The morphology of lipopigment granules in oligodendrocytes of the cerebellum and spinal cord and in Schwann cells of the N. ischiadicus of the cat, Japanese waltzing mouse, and albino mouse.

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The morphology of lipopigment granules in oligodendrocytes of the cerebellum and spinal cord and in Schwann cells of the N. ischiadicus of the cat, Japanese waltzing mouse, and albino mouse.