Retrograde Oxidative Reactions after Section of the Rubrospinal Tract

RETROGRADE OXIDATIVE REACTIONS AFTER SECTION OF THE RUBROSPINAL TRACT MAURICE HANSON, MONROE COLE, andJOHN A. MOLINSKI* The more basic, nay simple, the observation, the more will its significance elude interpretation. The following is an illustration of this axiom. More than three-quarters of a century ago Franz Nissl [1] developed the first adequate method for histological staining ofthe neuron. He also made the very useful observation that certain predictable changes occur in the neuronal soma after lesions of its axon. The various nuances of age of animal, type of animal, distance of lesion from soma, as so well discussed by Van Gehuchten [2], need not concern us here. What shall concern us, however, is the significance of the changes observed by Nissl vis-à-vis the physiological state of the cell. We shall refer to those changes described by Nissl after tearing the facial nerve of the rabbit as chromatolysis—a term actually coined by Marinesco [3]. Nissl interpreted the changes to be a regressive cell change, while Marinesco, 4 years later, considered them to indicate regenerative attempts of the cell. If one confines himself to the experimental model of Nissl or Marinesco, then the problem is insoluble and, indeed, both are probably correct. Lesion of the axon not confined to the central nervous system causes chromatolysis in the cell body but parallel regenerative sprouting from the distal end of the central stump. Is the process of regeneration, or some part thereof, the signal for chromatolysis? Regeneration is not such a signal after section of the central axon of a dorsal root ganglion cell, in spite of a regenerative response. This may simply be a quantitative matter related to rate of axon production [4]. But even when axon sprouting is severely impeded after section of a spinal or cranial motor neuron (e.g., by scar, neuroma, etc.), a flagrant chromatolytic response may be seen. *Department of Neurology, Highland View Hospital and Case Western Reserve School of Medicine, Cleveland, Ohio 44122. Supported in part by NIH grant NS 09926-02. Perspectives in Biology and Medicine · Spring 1976 | 381 We have approached this problem by comparing histological response to amount of the mitochondrial oxidative enzyme, TPNH diaphorase, as judged by histochemical methods. These parameters have been compared in three neuronal models: (a) peripheral axon, (b) central nervous system axon, and (c) central nervous system axon the perikaryon of which is known to undergo typical chromatolysis. Specifically, we have chosen (a) the facial and hypoglossal nerves, (b) medial lemniscus, and (c) rubrospinal tract. The results in a and b have been previously reported in detail [5]. All studies were performed on adult cats. The experimental series is shown in table 1 . Typical chromatolysis occurred in the neurons of the seventh and twelfth cranial nuclei and the nucleus ruber, pars magnocellularis. The neurons of nuclei cuneatus and gracilis were diminished in number and size and less intensely basophilic in tinctoral properties. The TPNH diaphorase staining was decreased in cuneatus and gracilis and increased in facial and hypoglossal nuclei. We interpreted the data to mean that oxidative enzyme activity is an expression of metabolism directed toward regeneration. In the nucleus ruber, enzyme activity is increased in animals surviving 1-6 days, but decreased in survivors of 16, 31, and 60 days, as depicted in figures 1 and 2 (see table 3). TABLE 1 Experimental Series: Entire Experimental Series Showing Type of Histological Preparation and Survival Times Animal NumberSurvival DaysPreparation 2 ..................... 45C 4 ..................... 60F 6 ..................... 1 C 7 ..................... 71F 9 ..................... 43C 11..................... 29C 12..................... 31F 13..................... 21C 15 ..................... 15C 16..................... 15F 17..................... 5 C 18..................... 5 F 22..................... 5 F 29..................... 3 F 30..................... 5 F 31..................... 1 F 33..................... 6 F 34..................... 4 F Note.—C = Celloidin, Cresyl Violet; F = Frozen, TPNH Diaphorase. 382 I Maurice Hanson et al. · Retrograde Oxidative Reactions Fig. 1.—TPNH diaphorase. Normal nucleus ruber, pars magnocellularis. RS-4. Survival 60 days; X 10. Fig. 2.—TPNH diaphorase. Abnormal nucleus ruber, pars magnocellularis. Decreased enzyme reaction. RS-4. Survival 60 days; X 10. It is therefore clear that oxidative enzyme metabolism is unrelated to chromatolysis per se (cf. tables 2 and 3). We suggest that the increased enzyme activity in the neurons...