VII INTERNAL FACTORS 643 



more extensive regeneration, of the whole body, in Platyhelminths and AnneHds, 

 involves the whole of the nervous system, and the power to promote regeneraton 

 grades downwards from the brain in all directions (Brondsted, 1955)- However, 

 here also, higher levels of the nervous system inhibit regeneration at posterior 

 levels in the body (Watanabe, 1935). 



It seems likely that there is a close relationship between the neurotropic action during 

 regeneration and the tropic action of innervation on normal growth and on maintenance 

 (Wyburn-Mason, 1950), though clearly there are features peculiar to regeneration. More 

 uncertain is the relationship between the tropic effects in general and the normal functional 

 activity of the nervous system (Huxley and De Beer, 1934; Needham, 1952). Innervation 

 without actual conduction-activity is adequate for the maintenance of end-organs. On the 

 other hand the latter further hypertrophy in response to function, and proportionately 

 to it. Nerve-tissue itself shows functional hypertrophy (Eccles, 1953, p. 200-2) and this in 

 its properties is distinct from the conduction processes, though causally dependent on them. 

 An eye-regeneration factor from the brain of Planarians does not travel via the optic nerve 

 (Lender, 1954). In sensory nerves the tropic effect must act antidromically (Lewis, 1937)- 



Nevertheless there is considerable evidence of significant similarities between the two 

 activities of nerve tissue. Acetyl choline (ach) and other cholinergic drugs, e.g. pilocarpine, 

 in low concentration, stimulate regeneration, and atropine retards (Morgulis, 1909; Paul- 

 ain, 1938; Welsh, 1946; Wyburn-Mason, 1950; Lecamp, 1954). Reciprocally ephedrine, 

 epinephrine and adrenalin, — neurological antagonists of cholinergic drugs, — inhibit 

 mitosis in the P-phase of regeneration (Friedwald and Buschke, 1944). 



Nerve-conduction and muscular contraction themselves, and no doubt response-mechan- 

 isms in general, resemble low-grade stress-reponses in their anaerobic, glycolytic initial 

 phase, and their aerobic recovery-phase, during which protein and nucleic acids are syn- 

 thezised (Hyden, 1943). The influx of Na and efflux of K following trauma compare with 

 their movements across the membrane of a conducting nerve-axon (Eccles, 1953), and the 

 growth of cells is accompanied by the reverse movements of these ions (Fenn, 1940). Cells 

 removed from the body into culture-media regularly lose K and take up Na : and the move- 

 ments are reversed when they begin to grow (p. 621). Anaerobic conditions favour the 

 first phase and aerobic the second. 



Acetyl choline accelerates the inflow of Na into cells and atropine its extrusion (Ussing, 

 1954). This is in harmony with the fact that Ach induces shock (Sevag, 195 1), the first 

 phase of the GAS (p. 609). It also induces inflammation (Lecamp, 1954), as in the initial 

 stages after trauma (Menkin, 1950). The shock and countershock phases of the GAS are 

 respectively cholinergic and adrenergic in type (Selye, 1948). Adrenalin tends to act syner- 

 gistically with the hormones of the cortex of the adrenal (Derbes and Weiss, 1951). 



These two phases probably correspond to the "ebb" and "flow" periods following trauma 

 (Cuthbertson, 1944; Needham, 1955), i.e. both are within the R-phase. Conceivably cho- 

 linergic drugs promote regeneration solely by virtue of this early action, but they generally 

 promote anabolic, and adrenalin catabolic activities, so that it seems probable that there 

 are two cholinergic phases, with an intervening adrenergic phase. Other bicyclic oscilla- 

 tions (Table 8, p. 610) may be related to this. The mineralocorticoids promote both 

 inflammatory reactions and cell-proliferation (Selye, 1955) and so possibly dominate 

 activity both before and after the phase of maximal activity of the S-group. 



The nature of the neurotropic factor (s) is still very uncertain. The factor of Overton ( 1 950) 

 which stimulates mitosis in surrounding tissues is resistant to freeze-drying and to alcohol 

 and ether, but is inactivated by acetone. It is insoluble in alcohol-ether, and therefore 

 could be a protein-derivative. Lender's "organisine" which induces the regeneration of 

 eyes in Planarians is stable to 70% alcohol and to heat, which would destroy most proteins. 

 It is not species-specific, but is readily diffusible, so that a relatively small, hydrophil 

 molecule is probably indicated. 



Factors which promote the regeneration of nerves themselves may be quite different 

 from these "heterotropic" factors. The "NR" factor of Koechlin and Von Muralt (1946), 



Literature p. 64g 



