Chemical Injury of the Spinal Cord of the Rabbit after Intracisternal Injection of Gentamicin

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Abstract
We previously reported that rabbits with quadriplegia, after a single intracisternal injection of gentamicin sulfate, have multiple minute lesions in the white matter of the upper cervical spinal cord and the lower medulla oblongata, most marked at the C2 segment, when light microscopy is used to study the histopathologic changes. Using electron microscopy in the present investigations, we have found that 9 hours after injection of gentamicin sulfate there was marked edema of fibrous astrocytes in the soma and processes of glia limitans. Ribosomes were disarranged. Mitochondria were swollen, the matrix density was increased and contained paracrystalline lattice structure, and the cristae were reduced in number. Oligodendrocytes displayed hypertrophy, with proliferation of smooth ER, ribosomes, microtubules, Golgi complexes, and lysosomes. A few axons were subsegmentally swollen due to axoplasmic edema. At 24 hours, the lesions became obvious by light microscopy. Astrocytes were more edematous and oligodendrocytes remained hypertrophic. Myelin sheaths were tumefied by dissociation of myelin lamellae. Axons were edematously swollen. Lysed axons were surrounded by lysed myelin sheaths. At 48 hours, numerous neuroaxonal end bulbs were formed at the lysed end. Wallerian degeneration was also evident. The data suggest that oligodendroglia actively react to detoxify gentamicin, astroglia become severely edematous but survive, and axons and myelin sheaths are lysed in reaction to the toxicity of gentamicin. The unique distribution of gentamicin lesions in the deeper white matter, with sparing of the overlying marginal myelinated fibers, seems to depend primarily upon the distribution of edematous astrocytes, which are most sensitive to this noxious chemical. Since gentamicin is apparently detoxified by oligodendroglia, the regenerative process of axons starts after a short period of axonal lysis.

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