Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats
Darko Perovic et al. J Orthop Surg Res. 2019.
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.
Keywords: BPC 157; Injury; Rats; Spinal cord.
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Conflict of interest statement
The authors declare that they have no competing interests.
Figures Fig. 1
Tail motor function (a, b) in rats that underwent spinal cord injury. Thirty days following injury. Debilitated rats underwent spinal cord injury that received saline post-injury (a). Contrarily, rats that had received BPC 157 (b) exhibit tail motor function rescue and consistently better motor function than the corresponding controls (a) Fig. 2
In rats that underwent spinal cord injury, debilitated and rescued tail motor function (BPC 157 (200 or 2 μg/kg) or saline 5 ml/kg intraperitoneally at 10 min after injury) presented by tail motor function score. Mark presents median score, and vertical bars correspond to maximum and minimum score. *P < 0.025 vs. control Fig. 3
In rats that underwent spinal cord injury, debilitated and rescued tail spasticity (BPC 157 (200 or 2 μg/kg) or saline 5 ml/kg intraperitoneally at 10 min after injury) according to Bennett scoring. Mark presents median, and vertical bars correspond to maximum and minimum score. *P < 0.025 vs. control Fig. 4
Microscopic presentation of lateral columns of rat spinal cord at the lesion site. a Ten minutes after injury, all animals have numerous fields of hemorrhage—arrowheads. b–d Histology 30 days after injury: b control animals, numerous confluent vacuoles—arrows; c BPC 157 2 μg/kg, few small vacuoles—arrows; d BPC 157200 μg/kg, only occasionally small vacuoles—arrows. Staining H&E, magnification × 300 Fig. 5
Microscopic presentation of posttraumatic spinal cord changes in the intermediate gray matter at the lesion site. a Ten min after injury, all animals have no difference compared to healthy animals. b–d Histology 30 days after injury: b control animals, huge edema and loss of neurons; c BPC 157 2 μg/kg, minimal edema changes and occasionally loss of neurons; d BPC 157 200 μg/kg, no difference to healthy animal. Staining H&E, magnification × 300 Fig. 6
A number of myelinated axons with diameter ≥ 7 μm in rat caudal nerve per 10,000 μm2 in corresponding days. Columns present mean and vertical bars standard deviation. P value *P < 0.05 BPC 157 groups vs. saline. +P < 0.05 saline and BPC 157 groups vs. laminectomy animals
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