Louis R. Nelson

Ultrastructure of Axonal Reaction in Red Nucleus Of CAT

Described here are ultrastructural changes in neurons of feline red nucleus exhibiting axon reaction after unilateral rubropsinal tratotomy at the C-2 level and surviving 2 to 65 days. Ultrastructural alterations included neurofilamentous hyperplasia; proliferation of smooth ER; temporary disappearance of organized granular ER with partial substitution by haphazardly arranged, broad cisternal profiles; loss of rosette ribosomes and occurrence of single ribonucleoprotein granules or an intercisternal amorphous density; increased numbers of subsurface cisterns and allied structures, often disposed in stacks; vesiculation and vacuolation of Golgi cisternae; prevalence of autophagic bodies derived in part from Golgi complexes; probable mitochondrial hyperplasia and various qualitative changes in these organelles; an increase in lipofuscin. Dendritic changes paralleled those of perikarya save that proliferation of subsurface cisterns and autophagic bodies was absent. Abnormalities of myelinated axons and boutons occurred and may have originated from retrograde degeneration of cortical neurons induced by lateral funiculotomy. Some perikarya were devoid of axosomatic boutons. Ultrastructural changes varied with the length of postoperative survival and were, at least partly, reversible. Chromatolysis was detectable light microscopically before ultrastructural abnormality appeared. The bearing of transneuronal mechanisms on axon reaction of central neurons and the protective effect of section of axons beyond the site of origin of collaterals are discussed.

Ultrastructural features of a brain injury model in cat

SummaryWe 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.

The effects of temperature and inhibitors on HCO3−- stimulated swelling and ion uptake of monkey cerebral cortex

In the presence of high concentrations of K+, additions of HCO3- as low as 0.35 mM caused a 23% increase in swelling, and concomitant increases in the chloride content of incubating monkey cerebrocortical slices. The uptake of chloride was accompanied by increased uptake of sodium and was highly temperature dependent, showing a marked activation at approximately 30 degrees C. A similar temperature activation was also found for a Mg2+-dependent, HCO3-stimulated ATPase activity in monkey cerebral cortex, consistent with a possible role for this enzyme in the K+ and HCO3-dependent swelling process and its associated ion movements. K+-dependent, HCO3-stimulated cerebrocortical tissue swelling with uptake of Na+ and Cl- was inhibited by acetazolamide indicating that carbonic anhydrase was also involved. The addition of ouabain also inhibited swelling and K+ and Cl- uptake at low concentrations, but led to increased swelling at higher concentrations ( greater than 10 mum). A similar biphasic effect on swelling was also seen following addition of ethacrynic acid.

Incorporation of triated leucine by axotomized rubral neurons

Fourteen kittens, 7--10 weeks of age, were injected with [3H]leucine 0.5--24 h before sacrifice 1--30 days after unilateral high cervical rubrospinal tractotomy. Histoautoradiographs of the red nuclei were prepared and counterstained with thionin. Axon reaction, evident histologically 24 h after surgery, was manifested by central chromatolysis or diffuse cytoplasmic chromophobia. Partial reversion toward a normal cytologic appearance was apparent 10--30 days postoperatively. Nucleolar and nuclear shrinkage and cytoplasmic atrophy were conspicuous accompaniments of axon reaction in rubral neurons. Expressed per cell the radioactivity of axotomized rubral nerve cells was consistently less than controls in animals surviving operation from 5 to 30 days. The data indicate that axon reaction in red nucleus is regressive in character and early associated with diminished protein synthesis. The frequently regressive nature of axon reaction in intrinsic neurons, such as those of red nucleus, probably is important in accounting for failure of regeneration of many mammalian CNS fiber tracts after injury.

Banding of rubro-olivary terminations in the principal inferior olivary nucleus of the chimpanzee

An electrolytic lesion centered just dorsal to, and grazing the superior surface of, the rostral red nucleus (RNr) was produced stereotactically in a single chimpanzee. Perikarya of the ipsilateral RNr exhibited retrograde cell changes, demonstrating interruption of its efferent fibers. The degenerated rubro-olivary tract was followed in silver impregnated material to the ipsilateral compact part of the pedunculopontine nucleus, pontine reticular formation and inferior olivary complex. Within the inferior olivary complex, terminations were banded and restricted to the principal subnucleus.