Environmental stressors affect intestinal permeability and repair responses in a pig intestinal ischemia model

Abstract

The pig is a powerful model for intestinal barrier studies, and it is important to carefully plan animal care and handling for optimal study design as psychological and physiological stressors significantly impact intestinal mucosal barrier function. Here, we report the effects of a period of environmental acclimation versus acute transport stress on mucosal barrier repair after intestinal ischemic injury. Jejunal ischemia was induced in young pigs which had been allowed to acclimate to a biomedical research housing environment or had been transported immediately prior to experimental injury (non-acclimated). Mucosa was then incubated ex vivo on Ussing chambers. In uninjured mucosa, there was no difference in transepithelial electrical resistance (TEER) or epithelial integrity between groups. However, acclimated pigs had increased macromolecular flux as compared to non-acclimated pigs during the first hour of ex vivo incubation. Ischemia induced greater epithelial loss in non-acclimated pigs as compared to acclimated pigs, yet this group achieved greater wound healing during recovery. Non-acclimated pigs had more robust TEER recovery ex vivo following injury versus acclimated pigs. The expression pattern of the tight junction protein claudin-4 was disrupted in acclimated pigs following recovery but showed enhanced localization to the apical membrane in non-acclimated pigs following recovery. Acute transport stress increases mucosal susceptibility to epithelial loss but also primes the tissue for a more robust barrier repair response. Alternatively, environmental acclimation increases leak pathway and diminishes barrier repair responses after ischemic injury.

Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion

“…It is noteworthy that injection of rhANGPTL4 in vivo blocked VEGF-driven separation of the VEGFR2/VE-cad complexes, reduced myocardial infarct area and the no-reflow degree in animals. ANGPTL4 exhibited a therapeutic vasculoprotection on no-reflow and exerted cardioprotection[ 23 - 26 ].…”

Gut Health and Influencing Factors in Pigs

“…Scientific works of literature regarding gut health have analyzed GIT characteristics (intestinal histology, morphology (influenced by prenatal and postnatal environment), barrier integrity (measurement of the transepithelial electrical resistance: TEER), immune response, and alteration of microbiome composition) in assessing gut health as these characteristics affect the functionality of the GIT, thereby affecting the performance of the animal [ 61 , 62 , 63 , 64 , 65 ]. Furthermore, the intestine’s certainty of exposure to foreign substances and microbial pathogens is a critical source of reactive oxygen species (ROS).…”

Age-Dependent Intestinal Repair: Implications for Foals with Severe Colic

“…A porcine model of early weaning stress has been able to recapitulate the effects on human infants in an experimental setting, and may be applicable to weaning stress in horses as well [ 33 ]. In a surgical ischemia model, it has also been noted that juvenile pigs subjected to acute transport stress on the day of intestinal ischemic injury exhibit increased intestinal injury but accelerated epithelial restitution when compared to pigs that experienced more protracted psychosocial stress related to prolonged changes in housing environment prior to injury [ 75 ]. These findings all indicate that stress responses early in life are likely to have major impacts on intestinal repair in foal colic cases.…”