Hippocampal Neuroprotection by Minocycline and Epigallo-Catechin-3-Gallate Against Cardiopulmonary Bypass-Associated Injury

Brain Pathol. 2015 Nov;25(6):733-42. doi: 10.1111/bpa.12242. Epub 2015 Feb 15.

Abstract

Surgical correction of congenital cardiac malformations mostly implies the use of cardiopulmonary bypass (CPB). However, a possible negative impact of CPB on cerebral structures like the hippocampus cannot be neglected. Therefore, we investigated the effect of CPB on hippocampus CA1 and CA3 regions without or with the addition of epigallocatechin-3-gallate (EGCG) or minocycline. We studied 42 piglets and divided them into six experimental groups: control without or with EGCG or minocycline, CPB without or with EGCG or minocycline. The piglets underwent 90 minutes CPB and subsequently, a 120-minute recovery and reperfusion phase. Thereafter, histology of the hippocampus was performed and the adenosine triphosphate (ATP) content was measured. Histologic evaluation revealed that CPB produced a significant peri-cellular edema in both CA regions. Moreover, we found an increased number of cells stained with markers for hypoxia, apoptosis and nitrosative stress. Most of these alterations were significantly reduced to or near to control levels by application of EGCG or minocycline. ATP content was significantly reduced within the hippocampus after CPB. This reduction could not be antagonized by EGCG or minocycline. In conclusion, CPB had a significant negative impact on the integrity of hippocampal neural cells. This cellular damage could be significantly attenuated by addition of EGCG or minocycline.

Keywords: EGCG; cardio-pulmonary bypass; hippocampus; histology; minocycline.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis Inducing Factor / metabolism
  • Brain Edema / drug therapy
  • Brain Edema / metabolism
  • Brain Edema / pathology
  • CA1 Region, Hippocampal / drug effects*
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / pathology
  • CA3 Region, Hippocampal / drug effects*
  • CA3 Region, Hippocampal / metabolism
  • CA3 Region, Hippocampal / pathology
  • Cardiopulmonary Bypass / adverse effects*
  • Caspase 3 / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Minocycline / pharmacology*
  • Neuroprotective Agents / pharmacology*
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Swine
  • Tyrosine / analogs & derivatives

Substances

  • Apoptosis Inducing Factor
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Neuroprotective Agents
  • Poly Adenosine Diphosphate Ribose
  • 3-nitrotyrosine
  • Tyrosine
  • Adenosine Triphosphate
  • Catechin
  • epigallocatechin gallate
  • Caspase 3
  • Minocycline