CAE-Induced Pancreatitis

Acute pancreatitis is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and causal treatment options are not available. Much of our current knowledge regarding the onset of pancreatitis stems from animal or isolated-cell models. There are several reasons why these models have been used: 1) the pancreas is a rather inaccessible organ because of its anatomical location in the retroperitoneal space, and 2) patients who are hospitalized with acute pancreatitis have usually passed through the initial stages of the disease where the triggering early events could have been studied. The advantages of animal models are the possibility to isolate specific aspects of a complex and varying disease course, the high degree of standardization and reproducibility, and the reduction of the required sample size eliminating variability in the study population. 

Caerulein (CAE)-Induced Pancreatitis

The model of caerulein-induced pancreatitis in rodents has been widely used and is one of the best characterized models in the literature.  The caerulein model of experimental pancreatitis is now widely used for the analysis of intracellular events in the early phase of pancreatitis. The model offers several advantages: it is non-invasive since no surgical intervention affecting the bile duct or pancreatic duct is necessary, it allows easily controlled grades of injury, it is highly reproducible, and it is applicable in several animals’ species such as mice and rats.

At Biomodels, animals are administered five (5) doses of caerulein (CAE) spaced one hour apart.  Exactly 5 hours after receipt of the first dose of CAE, animals are anesthetized using isoflurane and a small incision is made in the abdomen to expose the pancreas. Using a laser Doppler system (OxyFlo- Oxford Optronics, Ltd.) a laser flow probe is placed in three separate locations on the pancreas and blood flow is recorded for 30 seconds (10 values). The location of the probe placement is consistent among all animals assessed. Once the recordings are complete, the animals are euthanized via carbon dioxide inhalation and blood can be collected via cardiac puncture. Blood samples can be analyzed for hematocrit (RBC counts) using a CBC.  Additional blood samples can be processed for serum, and the pancreas can be removed and stored for further histological processing. The typical study design is summarized below, and validation data is found in the figure. 

Study Design Table

Caerulein Dose Dosing Route/ Schedule Pancreas Blood Flow- Doppler Analysis Serum/ Tissue Collection
CAE- 10µg/kg/dose I.P. – 5 Doses (t= 0, 1, 2, 3, 4 hrs) Once @ t = 5 hrs Blood for CBC, Serum, Pancreas

 

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