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Pentadecapeptide BPC 157 counteracts intracranial hypertension and thereby, severe portal and caval hypertension and aortal hypotension, widespread thrombosis, gastric and duodenal lesions in rats

Aim. In rats with intracranial hypertension (IH), we studied the severe gastric and duodenal lesions along with the severe portal and caval hypertension and aortal hypotension and widespread thrombosis with the superior sagittal sinus (SSS) ligation and central blood flow stasis, the disturbances instantly progress toward the periphery and rapidly perpetuate downhill injurious circle. Recently, as a possible resolving solution, pentadecapeptide BPC 157 therapy, (for review: Curr Pharm Des 2018 ; 24:1990-2001) has been used in alleviating vascular occlusion disturbances, and thereby further applied in rats with the SSS ligation. In rats with inferior caval vein (ICV) occlusion, BPC 157 counteracted venous hypertension and aortal hypotension, and thrombosis formation (Vascul Pharmacol 2018 ; 106:54-66). Likewise, BPC 157 counteracted bile duct ligation- induced liver cirrhosis and portal hypertension (Eur J Pharmacol 2019 ; 847:130-142). Methods. To evaluate IH, we made 2 burr holes in anesthetized rats, each approximately 2 mm laterally from the middle of the sagittal suture, and a 5-0 Vicryl suture was used to make a ligation in the middle of the SSS. Then, we made a single burr hole in the rostral part of the sagittal suture, above the SSS, and cannulated SSS anterior part by Braun intravenous cannules, and measured intravascular pressure, before and after medication (BPC 157 10µg, 10ng/kg, 1 ml/rat given topically at the swollen brain ; or ig or ip, while controls received an equal volume of 0.9% NaCl, topically ; or ig or ip).Portal and caval hypertension and aortal hypotension and thrombosis and gastric and duodenal lesions were assessed as described (Vascul Pharmacol 2018 ; 106:54- 66) at 15 min, 24 h and 48 h following sinus occlusion. Results. As shown (Fig. 1), SSS ligation disturbed pressure in SSS (negative between -26--28 mmHg (healthy) toward positive over 20), induced portal hypertension (healthy 3-5 mm Hg toward over 20 mmHg), caval hypertension (healthy 3-5 mm Hg toward over 20 mmHg) and aortal hypotension (below 80 mmHg) and widespread thrombosis (SSS, portal vein (PV), ICV, superior mesenteric vein (SMV), lineal vein (LV), abdominal aorta (AA)), gastric (7±1 mm(15 min), (10±1 (24 h), (10±2 (48 h)) and duodenal (5±1 mm(15 min), (12±2 (24 h), (11±3 (48 h))lesions. While venography studies (into SSS, external jugular vein, ICV) show collaterals rapid presentation, centrally and peripherally, all BPC 157 regimens rapidly reverse brain swelling, and the consequences of the SSS ligation. SSS, portal, caval and aortal pressure were close to normal. Venous and arterial thrombosis were markedly attenuated. Gastric and duodenal lesions were attenuated (Fig. 2). Conclusion. BPC 157 counteracts IH, and thereby, severe portal and caval hypertension and aortal hypotension, widespread thrombosis, gastric and duodenal lesions.

intracranial hypertension ; BPC 157 ; superior sagittal sinus ligation

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