The Effect of BPC 157 on Ischemic/Reperfusion Injuries in Rat Brain
Authors: vukojevic jaksa , Vrdoljak Borna , Malekinusic Dominik , Zaler Dora , Kolenc Danijela , Siroglavic Marko , Aralica Gorana , Drmic Domagoj , Seiwerth Sven , Sikiric Predrag 
Published: November 2023

Ischemic/reperfusion injuries are elementary pathophysiological findings in stroke and stroke is the third most common cause of death in the modern world and the first cause of long‐term disability. Pentadecapeptide BPC 157, has already been proven to have an effect on vessel integrity, it is a mediator of Robert's cytoprotection and interacts with the NO system, all of which, make it a promising agent when it comes to cerebral ischemic/reperfusion injuries. In this experiment, ischemic/reperfusion injuries are induced using bilateral carotid artery occlusion (BCAO). The effect of BPC 157 on ischemic/reperfusion injuries was investigated in male Wistar Albino rats. After an occlusion of 20 min, the rats were randomly divided into groups. The treated group received BPC 157 (10μg/kg, 10ng/kg, I.P.) right after surgery, while the control group received saline (1ml, I.P.) immediately after surgery. In addition, to test the relation with the nitric oxide (NO) system, we created three new groups, to which we administered L‐NAME (5 mg/kg, I.P.) alone, in combination with L‐arginine (100mg/kg, I.P.) or BPC 157 (10μg/kg, 10ng/kg, I.P.) respectively. After a reperfusion period of 24 or 72 hours, the neurological assessment was performed and samples were gathered for further examination. Neurological assessment was conducted using the Morrison water maze test (MWMT) and beam walk test (BWT). In the MWMT the control animals had far greater memory loss and spatial orientation loss, while the BPC 157 treated group had almost no loss in the MWMT. The control group lost 10.3 seconds, while the BPC 157 treated group gained 1 second in comparison to the training results. In the beam walk test, we also observed substantial differences between the control and treated group, where the control group walked far worse and scored 1, while the BPC 157 treated group walked much better and scored 4. The animals treated with L‐NAME lost 16.4 seconds in the MWMT and scored 0 in the BWT. When L‐NAME was administrated along with L‐arginine, it showed slight improvement, 6.2 in MWMT and scored 2 in BWT, while the combination of L‐NAME and BPC 157 abolished all the negative effects of L‐NAME and scored 3 in the BWT and lost 3.6 in the MWMT. The pathology findings concurred with the results obtained in the neurological assessment. Pentadecapeptide BPC 157 showed that it counteracts ischemic/reperfusion injuries, saving the rats from memory and orientation loss, as well as maintaining their motor capabilities. Along with that it can successfully counteract the negative effects of NO system inhibition, even moreso than L‐arginine, and thereby confirming its close relation to the NO system. The results we present here are promising and prove that BPC 157 has potential as a neuroprotective agent in cerebral ischemic/reperfusion injuries, although further investigations should be conducted to further confirm the full effects of BPC 157.

Support or Funding Information

This research was supported from Ministry of Science, Education and Sports, Republic of Croatia (grant number 108‐1083570‐3635)