The FESSH Diploma Examination in hand surgery. Federation of the European Societies for Surgery of the Hand.
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Clinical Competence↗
Biomedical subjects
A K Nachemson
Publications and source records attributed to A K Nachemson.
Does pain damage spinal cord neurons? Transsynaptic degeneration in rat following a surgical incision.
In prior studies, rats with a chronic constriction injury to the sciatic nerve have been found to have small- to medium-sized, pyknotic, and hyperchromatic neurons ('dark neurons'; DNs) in spinal dorsal horn laminae I-III. It has been proposed that DNs are produced by an excitotoxic insult involving N-methyl-D-aspartate receptor activation subsequent to ectopic nociceptor discharge, and that at least some DNs are inhibitory interneurons whose functional impairment or death contributes to a central state of hyperexcitability that underlies neuropathic hyperalgesia and allodynia. We show here that laminae I-III DNs are also present 2 days after a surgical procedure that does not include major nerve damage. We propose that this is also the result of a nociceptor-driven excitotoxic insult and that the functional impairment of the affected neurons may contribute to postoperative pain and tenderness.
Animals↗
Insulin-like growth factor I promotes nerve regeneration: an experimental study on rat sciatic nerve.
Insulin-like growth factor I (IGF-I; somatomedin C) has previously been demonstrated, with immunohistochemical methods, to accumulate locally at the site of trauma of an injured peripheral nerve. In the experiments reported here a Y-shaped silicone-chamber system was used to test if local infusion of IGF-I had supportive effects on nerve regeneration. The proximal end of a cut sciatic nerve was inserted into one channel of the Y-shaped chamber and the length and growth direction of the regenerating myelinated axons were evaluated after 1 month. When IGF-I (250 micrograms/ml 0.5 microliters/h) was infused into one channel by an osmotic pump, the length of the regenerating axons increased significantly compared to the control groups with no IGF-I added. In some instances the regenerating axons grew towards the osmotic pump. It is concluded that local infusion of IGF-I at appropriate concentration promotes regeneration of a peripheral nerve. It exerts a neuronotrophic but not a clear chemotactic effect.
Animals↗
Neurotropism in nerve regeneration: an immunohistochemical study.
A rectangular pseudomesothelial-lined chamber was used to elucidate the hypothesis that in adult rats neurotrophic factors are formed after nerve injury and may influence regeneration of peripheral nerves. The proximal end of a cut sciatic nerve was inserted into one corner of the chamber. In one group of animals the distal end of the cut sciatic nerve was implanted in the diagonally opposite corner of the chamber. In another group we just introduced the proximal end of the sciatic nerve; no distal implant was used. The organization, length and direction of the nerve fibres, regenerating from the proximal end of the sciatic nerve, was visualized immunohistochemically with the aid of antibodies against neurofilaments at 2, 3 and 4 weeks after surgery. When a distal sciatic nerve segment was used, nerve fibres regenerating from the proximal cut end of the sciatic nerve showed an organized growth across the chamber, formed bundles and grew into the diagonally implanted nerve piece. If there was no distal implant, the growth of the randomly directed nerve fibres ceased after about two weeks, resulting in formation of a neuroma-like structure. Increased immunoreactivity of the trophic peptide insulin-like growth factor I (IGF-I, somatomedin C) was demonstrated in the regenerating nerve, most evidently in reactive Schwann cells. It is concluded that a positive neurotropic effect is exerted on growing nerve fibres by injured, reactive peripheral nerve tissue. There could tentatively be a relation between nerve regeneration and local formation of trophic factors.
Animals↗
Axonal regeneration and growth direction in square-shaped mesothelial chambers.
A preformed rectangular mesothelial chamber was used as an experimental model to study possible neurotrophic and chemotactic effects on outgrowing axons. The experiments were performed on rats. The proximal end of a severed sciatic nerve was introduced into one corner of the chamber. In the opposite or the diagonally opposite corner the distal end of the nerve or a nerve transplant was introduced leaving a gap of about 10 mm between the proximal and distal nerve segments. In other series a silicon tube was introduced into a distal corner and some chambers were kept closed distally. After three and six months respectively the contents of the chambers were analysed, using histological and neurophysiological techniques. In all cases there was a preferential growth of regenerating nerve fibres towards and into the distal nerve tissue regardless of the position in the chamber. With a silicon tube or no tissue at all introduced distally the regenerating axons grew only 3-5 mm. These experiments indicate that nerve tissue has a neurotrophic and chemotactic influence on outgrowing axons.
Animals↗
Visualization of regenerating sciatic nerve fibres by neurofilament immunohistochemistry.
Regeneration of injured sciatic nerve in rats was studied with an immunohistochemical technique visualizing neurofilaments in nerve fibres as well as S-100 protein in Schwann cells. Outgrowing axons with delicate sprouts could be demonstrated along pathways formed by Schwann cells. In contrast, axons which had stopped growing or were degenerating showed bulb-like swellings in their terminal parts. The use of immunohistochemical techniques offers advantages over conventional neurohistochemical staining methods, enabling more detailed observations of nerve regeneration mechanisms in animals.
Animals↗
Evidence indicating trophic importance of IGF-I in regenerating peripheral nerves.
The mechanisms influencing regeneration of peripheral nerves are incompletely known, but growth factors are supposed to play a key role. In the present study, we demonstrate, with the aid of immunohistochemical methods, that somatomedin C (Sm-C/insulin-like growth factor I/IGF-I) rapidly increased from low to high concentrations, reaching peak values in 2 weeks, in regenerating sciatic nerves of adult rats. In addition, IGF-I was demonstrated extracellularly, never observed in the control nerves. Reactive Schwann cells appeared to be the major source for IGF-synthesis. Higher concentrations were seen in tubulated nerves as compared to sutured ones. It is proposed that IGF-I exerts important growth supporting effects on regenerating peripheral nerves.
Animals↗
Tissue specificity in nerve regeneration.
In 1944 Weiss & Taylor presented experimental evidence against "neurotropism" in nerve regeneration. We used a silicone Y-chamber system to repeat some of those experiments. The proximal stump of transected rat sciatic nerve was introduced into the proximal inlet of the Y. One of the distal outlets was left empty, plugged or occupied by a tendon graft, the other outlet being occupied by a nerve graft. Analysis after 4 and 12 weeks showed in all cases a preferential or exclusive axonal growth towards the nerve piece. The results, indicating the existence of "tissue specificity", are contradictory to the results reported by Weiss & Taylor (30). The findings are discussed with respect to possible influence of humoral, cellular and molecular factors associated with the distal nerve stump as well as the matrix, formed between both nerve segments.
Animals↗
Nerve regeneration and pharmacological suppression of the scar reaction at the suture site. An experimental study on the effect of estrogen-progesterone, methylprednisolone-acetate and cis-hydroxyproline in rat sciatic nerve.
Pharmacological suppression of the scar reaction was tested as a possible method for improving axonal regeneration after transection and suture of the sciatic nerve of rats. The animals in the experimental groups were systemically treated post-operatively with estrogen-progesterone, methylprednisolone-acetate (Depomedrone) or cis-hydroxyproline. Only in the cis-hydroxyproline treated animals was there a tendency towards a decrease in fibroblastic activity at the suture site after 4 weeks. However, there was no difference in the growth of axons to the distal nerve segment after pharmacological treatment as compared to non-treated animals, when tested 12 weeks post-operatively. The motor nerve conduction velocity was however significantly greater in both the cis-hydroxyproline and the methylprednisolone-acetate groups as compared with the estrogen-progesterone and the control groups. In conclusion, cis-hydroxyproline and also methylprednisolone-acetate may improve the function of regenerating peripheral nerve, while estrogen-progesterone does not seem to have this effect.
Animals↗