Introduction
We focused on the improvement of the healing after traumatic nerve injury [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], transected rat sciatic nerve injury healing and a peptide therapy, using a small, orally active, anti-ulcer peptide [13], [14], [15], [16], [17], [18], [19], [20], [21], [22] — stable gastric pentadecapeptide BPC 157 (MW 1419) effective in trials for inflammatory bowel disease therapy [19], [20], [21], [22].
Knowing also BPC 157's wound healing capability, increased collagen and new blood vessels formation, decreased myeloperoxidase (MPO) activity and inflammatory cell influx, including healing of transected muscle and tendon [13], [14], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], we thought that it could also influence the healing of transected nerve injuries, although generalization is not always applicable, since for example, tacrolimus (FK506) does not have a consistent effect on wound healing [33]. Important fact is that BPC 157 has undoubtedly a positive effect on muscle healing [27], [28], [29], [30], providing the importance of the suggested regeneration of the damaged intramuscular nerve branches [34].
BPC 157 shares some characteristics with neuroimmunophilin ligands, of which tacrolimus (FK506) has emerged as a particularly promising therapeutic agent important in a nerve injury [1], [2]. Neuroimmunophilin ligands cross the blood–brain barrier and are orally effective in a variety of animal models of ischemia, traumatic nerve injury and human neurodegenerative disorders [1]. BPC 157 given peripherally also crosses the blood–brain barrier influencing region-specific serotonin synthesis in the rat brain [35], [36]. Unlike neuroimmunophilin ligands [3], it also exhibits a neurotropic effect attenuating 1-methyl-4-phenyl 1,2,3,6, tetrahydropyridine (MPTP) brain lesion and mortality [15].
Therefore, after sciatic nerve transection, BPC 157 was applied intraperitoneally, intragastrically or locally, at the site of anastomosis immediately after nerve anastomosis creation. In addition, after the nerve segment was dissected, BPC 157 was applied directly into the tube to completely fulfill the gap between the nerve stumps.
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Materials and methods
All experimental procedures were approved by the local Ethics Committee and assessed by the observers blinded about the treatment given. We used male Wistar Albino rats, 200 g body weight, randomly assigned, at least 10 rats per experimental group per period. The surgical procedures were performed under a dissection microscope (Opton, Oberkochen, Germany) in deeply anaesthetized rats (pentobarbital, 65 mg/kg i.p.). The right sciatic nerve was exposed and completely transected with microscissors,
Results
In general, the spontaneous course of the healing process of injured nerve was inadequate in all control rats regardless of the model used (Table 1, Table 2, Table 3, Table 4, Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5). We demonstrated that pentadecapeptide BPC 157 improved healing of the transected sciatic nerve, either anastomozed (Fig. 1, Fig. 2) or excised and nerve stumps inserted into the silicone tube (Fig. 3B,C,E,F), on postoperative weeks 4 (Fig. 1, Fig. 3) and 8 (Fig. 2, Fig. 3). While
Discussion
After traumatic injury, we presented a consistent failure of spontaneous healing of transected rat sciatic nerve exhibited in controls that was however fully counteracted by a marked improvement of healing induced by pentadecapeptide BPC 157 in anastomosed as well as non-anastomosed nerve (7 mm nerve segment resected), consistently in two different investigated models.
To evaluate the success of the applied therapy it should be noted that no carrier was used [14], [15], [16], [17], [18], [19],
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