Differential effects of intestinal ischemia and reperfusion in rat enteric neurons and glial cells expressing P2X2 receptors

Histol Histopathol. 2015 Apr;30(4):489-501. doi: 10.14670/HH-30.489. Epub 2014 Nov 17.

Abstract

Background: Intestinal ischemia followed by reperfusion (I/R) may occur following intestinal obstruction. In rats, I/R in the small intestine leads to structural changes accompanied by neuronal death.

Aim: The objective was to analyze the impact of I/R injury on different neuronal populations in the myenteric plexus of the rat ileum after different periods of reperfusion.

Methods: The superior mesentery artery was occluded for 45 minutes, and animals were euthanized after 24 hours and 1 week of reperfusion. Immunohistochemical analyses were performed with antibodies against the P2X2 receptor in combination with antibodies against nitric oxide synthase (NOS), choline acetyltransferase (ChAT), calbindin, calretinin, the pan-neuronal marker anti-HuC/D, or S100β (glial marker).

Results: Dual immunolabeling demonstrated that approximately 100% of NOS-, ChAT-, calbindin-, and calretinin-immunoreactive neurons in all groups expressed the P2X2 receptor. Following I/R, the neuronal density decreased in the P2X2 receptor-, ChAT-, calretinin-, and HuC/D-immunoreactive neurons at 24 hours and 1 week following injury compared to the densities in the control and sham groups. The calbindin-immunoreactive neuron density was not reduced in any of the groups. The density of enteric glial cells increased by 40% in the I/R group compared to the density in the sham groups. We also observed increases of 12%, 16%, and 23% in the neuronal cell body profile areas of the NOS-, ChAT-, and calbindin-immunoreactive neurons, respectively, at 1 week following I/R. However, the average size of the calretinin-immunoreactive neurons was reduced by 12% in the I/R group at 24 hours.

Conclusions: This work demonstrates that I/R is associated with a significant loss of different classes of neurons in the myenteric plexus accompanied by morphological changes and an increased density of enteric glial cells; all of these effects may underlie conditions related to intestinal motility disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Enteric Nervous System / pathology*
  • Immunohistochemistry
  • Intestinal Diseases / pathology*
  • Intestinal Mucosa / metabolism
  • Intestines / pathology
  • Male
  • Microscopy, Confocal
  • Neuroglia / pathology*
  • Neurons / pathology*
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P2X2 / biosynthesis
  • Reperfusion Injury / pathology*

Substances

  • Receptors, Purinergic P2X2