Hippocampal Neuroprotection by Minocycline or Epigallocatechin-3-Gallate against Cardiopulmonary Bypass-Associated Injury

Background: 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 anti-oxidant or anti-apoptotic drugs.

Methods: We studied 42 piglets (four weeks of age) and divided them into six experimental groups: control without or with epigallocatechin-3-gallate (EGCG) or minocycline, CPB without or with EGCG or minocycline. The piglets underwent 90min CPB and subsequently a 120min recovery and reperfusion phase. Thereafter histology of the hippocampus was performed and ATP content was measured.

Results: Histological evaluation revealed that CPB produced a significant peri-cellular edema in CA1 and CA3 regions. Moreover, markers for hypoxia, apoptosis and nitrosative stress were elevated. 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 significantly antagonized by EGCG or minocycline.

Conclusion: In our study, 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.