ABSTRACT
The use of a devitalized skeletal muscle graft and conventional nerve graft to repair a 5mm long segmentary sciatic nerve lesion was studied in rats by means of functional, morphometric and spinal cord motor neuron cell response evaluation. Thirty-four rats were used and divided into four groups according to the procedure: (1) sham operation; (2) conventional nerve grafting; (3) muscle grafting; (4) unrepaired lesion. The sciatic functional index (SFI) was evaluated every fortnight up to the 105th postoperative day by measuring three parameters in the rats' footprint. The animals of Groups 2 and 3 presented initial complete functional loss, followed by slow but steady recovery, with final similar SFIs. The histologic and morphometric studies showed an increased small diameter/thin myelin sheath nerve fiber density distally to the lesion site for both types of graft. An increased population of motor neurons was observed in the anterior horn of the lumbar spinal cord segment with both types of grafts, but not in the control groups. The SFI, histologic and morphometric data did not differ significantly between the two types of graft, thus indicating a similar behavior. The authors conclude that a 5mm long skeletal muscle graft works as well as a conventional nerve graft.
Subject(s)
Muscle, Skeletal/transplantation , Nerve Regeneration , Sciatic Nerve/transplantation , Sciatic Neuropathy/surgery , Animals , Cell Count , Disease Models, Animal , Male , Motor Neurons/metabolism , Muscle, Skeletal/physiology , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/transplantation , Rats , Rats, Wistar , Plastic Surgery Procedures/methods , Recovery of Function/physiology , Time Factors , Transplants , Wound Healing/physiologyABSTRACT
1. Bradykinin (Bk; Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg8) inactivation by bulk isolated neurons from rat brain is described. 2. Bk is rapidly inactivated by neuronal perikarya (4.2 +/- 0.6 fmol/min/cell body). 3. Sites of inactivating cleavages, determined by a kininase bioassay combined with a time-course Bk-product analysis, were the Phe5-Ser6, Pro7-Phe8, Gly4-Phe5, and Pro3-Gly4 peptide bonds. The cleavage of the Phe5-Ser6 bond inactivated Bk at least five fold faster than the other observed cleavages. 4. Inactivating peptidases were identified by the effect of inhibitors on Bk-product formation. The Phe5-Ser6 bond cleavage is attributed mainly to a calcium-activated thiol-endopeptidase, a predominantly soluble enzyme which did not behave as a metalloenzyme upon dialysis and was strongly inhibited by N-[1(R,S)-carboxy-2-phenylethyl]-Ala-Ala-Phe-p-aminobenzoate and endo-oligopeptidase A antiserum. Thus, neuronal perikarya thiol-endopeptidase seems to differ from endo-oligopeptidase A and endopeptidase 24.15. 5. Endopeptidase 24.11 cleaves Bk at the Gly4-Phe5 and, to a larger extent, at the Pro7-Phe8 bond. The latter bond is also cleaved by angiotensin-converting enzyme (ACE) and prolyl endopeptidase (PE). PE also hydrolyzes Bk at the Pro3-Gly4 bond. 6. Secondary processing of Bk inactivation products occurs by (1) a rapid cleavage of Ser6-Pro7-Phe8-Arg8 at the Pro7-Phe8 bond by endopeptidase 24.11, 3820ACE, and PE; (2) a bestatin-sensitive breakdown of Phe8-Arg9; and (3) conversion of Arg1-Pro7 to Arg1-Phe5, of Gly4-Arg9 to both Gly4-Pro7 and Ser6-Arg9, and of Phe5-Arg9 to Ser6-Arg9, Phe8-Arg9, and Ser6-Pro7, by unidentified peptidases. 7. A model for the enzymatic inactivation of bradykinin by rat brain neuronal perikarya is proposed.