Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats

Abstract

Background: We focused on the therapeutic effects of the stable gastric pentadecapeptide BPC 157 in spinal cord injury using a rat model. BPC 157, of which the LD1 has not been achieved, has been implemented as an anti-ulcer peptide in inflammatory bowel disease trials and recently in a multiple sclerosis trial. In animals, BPC 157 has an anti-inflammatory effect and therapeutic effects in functional recovery and the rescue of somatosensory neurons in the sciatic nerve after transection, upon brain injury after concussive trauma, and in severe encephalopathies. Additionally, BPC 157 affects various molecular pathways. Methods: Therefore, BPC 157 therapy was administered by a one-time intraperitoneal injection (BPC 157 (200 or 2 μg/kg) or 0.9% NaCl (5 ml/kg)) 10 min after injury. The injury procedure involved laminectomy (level L2-L3) and a 60-s compression (neurosurgical piston (60-66 g) of the exposed dural sac of the sacrocaudal spinal cord). Assessments were performed at 1, 4, 7, 15, 30, 90, 180, and 360 days after injury. Results: All of the injured rats that received BPC 157 exhibited consistent clinical improvement, increasingly better motor function of the tail, no autotomy, and resolved spasticity by day 15. BPC 157 application largely counteracted changes at the microscopic level, including the formation of vacuoles and the loss of axons in the white matter, the formation of edema and the loss of motoneurons in the gray matter, and a decreased number of large myelinated axons in the rat caudal nerve from day 7. EMG recordings showed a markedly lower motor unit potential in the tail muscle. Conclusion: Axonal and neuronal necrosis, demyelination, and cyst formation were counteracted. The functional rescue provided by BPC 157 after spinal cord injury implies that BPC 157 therapy can impact all stages of the secondary injury phase.

Occluded Superior Mesenteric Artery and Vein. Therapy with the Stable Gastric Pentadecapeptide BPC 157

“…Thus, we speculate that BPC 157 may counteract several steps of the syndrome that results from vessel occlusion. Finally, BPC 157 has been shown to attenuate brain lesions induced by trauma [71], spinal cord compression [72], or various encephalopathies [65][66][67][68][69][70]. BPC 157 also counteracted both early and delayed neural hippocampal damage in a rat stroke model (bilateral occlusion of the common carotid arteries) when therapy was given during reperfusion, leading to full functional recovery and restoration of recognition memory deficits [25].…”

In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro

“…Likewise, in rats with a severed sciatic nerve, BPC 157 markedly improves nerve healing and counteracts autotomy [35], which reflects chronic neuropathic pain, neuroma at the proximal nerve stump, and regenerative nerve sprouts growing into all directions, and prevents or at least significantly attenuates the chain of events otherwise leading to the painful sensation referred to the denervated region [78]. A corresponding autotomy counteraction appears in the L2-L3 spinal compression model, when the stable gastric pentadecapeptide BPC 157 improves the healing course of the spinal cord injury and leads to functional recovery in rats [79]. Also, much like lidocaine-induced arrhythmias, BPC 157 counteracts disturbances after bupivacaine [14], KCl overdose [15], digitalis overdose [16], hypoxia and reoxygenation [17], succinylcholine [18] neuroleptics and prokinetics [19], and doxorubicin [80].…”

Stable Gastric Pentadecapeptide BPC 157 and Wound Healing

“…Especially, BPC 157 exhibits both special muscle healing (i.e., after transection of major muscle (Figures 9,11,12), crush (Figure 10), and denervation (Figure 11) (Staresinic et al, 2006;Novinscak et al, 2008;Mihovil et al, 2009;Pevec et al, 2010)), and tendon healing (Staresinic et al, 2003;Krivic et al, 2006;Krivic et al, 2008) (i.e., after the Achilles tendon transection and detachment from calcaneal bone), or ligament healing (Cerovecki et al, 2010) (i.e., medial collateral ligament transection). In addition, along with function recovery (Figure 11), BPC 157 counteracts muscle disability related to various noxious procedures, after abdominal aorta anastomosis (Hrelec et al, 2009), L2-L3 compression (Perovic et al, 2019), severe electrolytes disturbances (Baric et al, 2016;Medvidovic-Grubisic et al, 2017), application of the succinylcholine (Stambolija et al, 2016), neuroleptics (Jelovac et al, 1999;Belosic Halle et al, 2017), or neurotoxin (MPTP, cuprizone) FIGURE 8 | Gene expression analysis and BPC 157 therapy. With the therapy done immediately after wounding, we performed the Akt1, Braf, Egfr, Egr1, Grb2, Hdac7, Kras, Mapk1, Mapk3, Mapk14, Nos3, Pik3cd, Plcg1, Prkcg, Ptk2, Pxn, Src, Srf, and Vegfa genes expression analysis (○, no significant change in gene expression; ▲, increased gene expression) in the rats' excision wound and in the skin and subcutaneous tissue, done at 2, 5, and 10 min following BPC 157 application.…”