Protective effect of cyclosporin A on brain injury in rats with acute necrotic pancreatitis

Aims: This study was designed to evaluate the protective effect of cyclosporin A (CsA) on brain injury in rats with acute necrotic pancreatitis (ANP) in order to provide a scientific basis for the use of the drug in treating brain injury caused by pancreatitis. Main methods: The rats were divided into a sham group, an ANP group and an ANP + CsA group. The ANP model was induced by administering 5% sodium taurocholate through the biliopancreatic duct. Five minutes before the preparation of the ANP model, 1 ml of CsA (10 mg/kg) was injected in a clinically used pharmaceutical formulation (Sandimmun (R)) via the dorsal vein of the penis. Twelve hours after the model was established, samples were taken from the rats in all groups for measurement of appropriate indexes. The serum levels of pro-inflammatory tumor necrosis factor-alpha (TNF-alpha), interleukin 113 (IL-1 beta), and anti-inflammatory interleukin 10 (IL-10) were determined by ELISA. The pancreatic mRNA expressions of these cytokines were evaluated by RT-PCR. Brain water content was tested by the dry-wet method, and brain malondialdehyde (MDA) content was detected by the chemical colorimetry method. Key findings: Both the serum levels and the pancreatic tissue mRNA expression of TNF-a and IL-1 beta, as well as the brain water content and brain MDA content, were significantly increased in the ANP group. CsA treatment noticeably reduced both the serum levels and the pancreatic mRNA expression of TNF-a and IL-1 beta and decreased brain water and MDA contents. In contrast to the pro-inflammatory cytokines, the serum levels and the pancreatic tissue mRNA expression of IL-10 were markedly increased by the injection of CsA. Significance: CsA could alleviate acute pancreatitis-associated brain injury. (C) 2010 Elsevier Inc. All rights reserved.