Energy substrate-supplemented resuscitation affects brain monocarboxylate transporter levels and gliosis in a rat model of hemorrhagic shock

Tom Lin, Elena Koustova, Huazhen Chen, Peter M. Rhee, John Kirkpatrick, Hasan B. Alam, John B. Cone

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background: Monocarboxylate (MC)-supplemented resuscitation has been shown to attenuate cellular injury after hemorrhagic shock. However, little is known about its effect on the central nervous system. The brain can use MCs such as lactate, pyruvate, and β-hydroxy-butyrate as energy substrates. The transit of MCs into the central nervous system is facilitated by the monocarboxylate transporters (MCTs), and their blockage can exacerbate neuronal damage. We examined the expression of MCT1 and markers specific for activation of astroglia and microglia in the brains of rats subjected to hemorrhagic shock and resuscitation. The hypothesis was that resuscitation with MC-based fluids would be accompanied by MCT1 up-regulation and glial response. Methods: Rats (n = 30) were subjected to volume-controlled hemorrhage. Test groups included: sham, no resuscitation, resuscitation with normal saline, resuscitation with racemic lactated Ringer's solution, resuscitation with pyruvate Ringer's solution, and resuscitation with β-hydroxybutyrate-containing ketone Ringer's solution. Plasma levels of MC were measured serially. The brains were investigated using GFAP, CD11b, CD43, MCT1, and GLUT1 immunohistochemistry. Results: Rats resuscitated with MC-containing fluids had increased levels of MCT1 in brain endothelial cells and neuropil compared with sham rats. Enhanced staining was localized to the choroid plexus, astrocytic end feet, and white matter structures. None of the resuscitation treatment induced astrocytic hyperplasia, and pyruvate Ringer's solution and ketone Ringer's solution resuscitation led to hypertrophy of astrocytes. Conclusion: In hemorrhagic shock, resuscitation with MC-based fluids increased brain MCT1 level and led to activation of astrocytes. Enhanced MC trafficking could be an essential route for energy supply to neurons under adverse circulatory conditions.

Original languageEnglish (US)
Pages (from-to)1191-1202
Number of pages12
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume59
Issue number5
DOIs
StatePublished - Nov 1 2005

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Keywords

  • Astrocytes
  • GFAP
  • GLUT1
  • Hemorrhagic shock
  • MCT1
  • Microglia
  • Monocarboxylates

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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