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Notes: Summary We present qualitative and quantitative ultrastructural observations on the changes induced in neuroglia and blood vessels of gray matter of cat brain by an experimental acceleration-deceleration injury which, when used alone, causes negligible morbidity and mortality, but, when combined with systemic hypoxia, leads to coma and delayed death in approximately 50% of experimental subjects. An increase in the proportion of neuropil occupied by astrocytic cytoplasm is detectable qualitatively in layer Vb of pericruciate cortex 20 min after injury without hypoxia, and is maximal (22%, as measured morphometrically, vs 11.4% in controls) 40 min afterward. Near-normal values (14.1%) are obtained 100 min following the insult. If trauma is succeeded 40 min later by a 60-min period of hypoxia, there is prolongation of astrocytic edema and other neuroglial accompaniments of the traumatic lesion, such as aggregation of nuclear nucleoprotein granules and, in astrocytes, fusion of rosette ribosomes and enlargement of mitochondria. A decrease in luminal area occurs in capillaries 40 min after trauma applied alone. Hypoxia without trauma leads to a significant increase in capillary luminal area, which, however, is abolished when trauma precedes the hypoxic interlude. Intravenous injection of a non-diuretic, fluorenyl derivative (L-644,711) of (aryloxy)alkanoic acid loop diuretics, completely prevents the astrocytic swelling ordinarily present 40 min after acceleration-deceleration injury. Also, L-644,711 improves mortality and morbidity scores in cats subjected to trauma with hypoxia. We suggest that astroglial swelling may be a critical step in the evolving pathology of this head injury model and its prevention, as by L-644,711 administration, may have relevance to the treatment of cerebral edema in human head injury and other clinical disorders accompanied by astrocytic swelling.

Notes: Summary Following left lateral funiculotomy, axons of cat pericruciate cortex exhibited neurofilamentous hyperplasia and complex, adaxonal, oligodendrocytic invaginations into electron-lucent or (commonly) electron-dense, degenerating axoplasm. These changes were absent from sham-operated and unoperated animals. Neurofilamentous hyperplasia was exclusively right-sided and appeared in myelinated axons 5–49 days postoperatively and in nonmyelinated axons 14–153 days after surgery. Oligoglial invaginations were present 1–49 days after surgery and were predominantly right-sided. Intramyelinic, axo-dendritic synapses appeared in operated cats 5–10 days postoperatively. Intra-axonal accumulations of ribosomes were found also. These changes also occurred exclusively or predominantly contralateral to spinal surgery. Other ultrastructural abnormalities, e.g., amorphous transformation of axoplasm and accumulations of dense bodies in intra-myelinic, dark cytoplasm, had a less certain relationship to lateral funiculotomy. The axonal alterations that were limited to operated cats possibly represent a true retrograde axonal degeneration occurring at a distance from the site of axonic interruption and unaccompanied by evidence of nerve cell death.

Notes: Summary Rat retinal ganglion cell layer (GCL) was examined ultrastructurally 1–180 days after intraorbital crushing of one optic nerve. It was confirmed quantitatively that axotomized ganglion cells lost cisternal membranes of the rough endoplasmic reticulum (RER) and showed disintegration of Nissl bodies and ribosomal rosettes 3 days postoperatively. Between 60 and 180 days after neurotomy there was partial reversion of the RER towards normal. At postoperative intervals of 14–60 days, chromatin aggregation became conspicuous and some nuclei were prominently furrowed and contained electron-dense inclusions. Concurrently, profiles of dead ganglion cells were encountered. Mean mitochondrial area increased in axotomized neurons but mitochondrial density declined, while the Golgi apparatus, lamellar specializations of the RER and the size of nuclei did not change significantly. Cytoplasmic atrophy was profound, however. Small nerve cells of the GCL appeared morphologically distinct from ganglion cells and did not undergo appreciable alteration. A decline in neuronal density, approximating 35%, occurred between the third and seventh postoperative day and progressed slowly thereafter. Neuronal density was 32% of normal 180 days postoperatively. A temporary increase in glial density 3–28 days after operation was due to microglial hyperplasia. Müller cell and astrocytic processes hypertrophied, infiltrated nerve fibre bundles, and surrounded and intruded into neuronal somata. Bundles of unmyelinated small axons, invested by astrocytes and basal lamina, were present within the necrotic cavity of the lesioned nerve 28–90 days postoperatively and had cytologic features of regenerative axonal sprouts. We conclude that intraorbital optic nerve crush is followed by a noteworthy degree of regenerative axonal sprouting which occurs and persists against a background of slow but relentless decline in the retinal ganglion cell population. This slow decline follows a rapidly-sustained loss of approximately one-third of the axotomized retinal ganglion cells during the first postoperative week. Intraorbital, as opposed to intracranial, injury of the optic nerve appears, paradoxically, to induce both a greater degree of ganglion cell death and a greater amount of regenerative axonal sprouting. Cytologic changes in axotomized retinal ganglion cells resemble those described for other populations of mammalian intrinsic neurons subjected to like injury. However, they differ, especially with regard to patterns of nuclear, nucleolar and RER alteration, from changes observed in peripheral neurons of mammals and intrinsic neurons of submammalian vertebrates that successfully regenerate severed axons. The neuroglial response in the surround of retinal ganglion cells after optic nerve crush is characterized by hypertrophy of astrocytes and Müller cells and a transient, modest increase of microglia. The microglial reaction is clearly less pronounced than that which occurs in the surround of axotomized peripheral neurons of the rat. The data presented here provide qualitative and quantitative cytologic information against which any effects exerted on the axotomy response and optic nerve regeneration by growth-promoting agents may be assessed.