Putative neurotrophic factors and functional recovery from peripheral nerve damage in the rat.
1. In rats, recovery of sensory-motor function following a crush lesion of the sciatic or tibial nerve was monitored by measuring foot reflex withdrawal from a local noxious stimulation of the foot sole. 2. Putative neurotrophic compounds were tested on this functional recovery model: melanocortins (peptides derived from ACTH (corticotropin) and alpha-MSH (melanotropin], gangliosides and nimodipine were effective whereas isaxonine and TRH (thyrotropin releasing hormone) were not. 3. Structure-activity studies with melanocortins revealed a similar effectiveness of alpha-MSH, [N-Leu4, D-Phe7]-alpha-MSH, desacetyl-alpha-MSH and the ACTH analogue ORG 2766, questioning the validity of the previously suggested notion that the melanotrophic properties of these peptides are responsible for their neurotrophic effect. 4. As recovery of function after peripheral nerve damage follows a similar time course in hypophysectomized (five days post operation) and sham-operated rats, effective melanocortin therapy does not mimic an endogenous peptide signal in the repair process from pituitary origin. 5. Subcutaneous treatment with ORG 2766 (7.5 micrograms kg-1 48 h-1) facilitates recovery of function following peripheral nerve damage in young (6-7 weeks old), mature (5 month old) and old (20 month old) rats. 6. In view of the diversity in structure of the effective neurotrophic factors and the complexity of nerve repair, the present data support the notion that peripheral nerve repair may be facilitated by different humoral factors likely to be active on different aspects of the recovery process.
Department of Medical Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht, The Netherlands.
C E
CE
Van der Zee
J H
JH
Brakkee
W H
WH
Gispen
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D005260:Female; D007016:Hypophysectomy; D009074:Melanocyte-Stimulating Hormones / Q000031:analogs & derivatives / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D011743:Pyrimidines; C013765:Org 2766; D009553:Nimodipine; C020375:isaxonine; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones