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 Citations (Scopus)

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
Volume59
Issue number5
DOIs
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

Gliosis
Hemorrhagic Shock
Resuscitation
Brain
Pyruvic Acid
Astrocytes
Ketones
Central Nervous System
Hydroxybutyrates
Choroid Plexus
Neuropil
Butyrates
Microglia
Neuroglia
Hypertrophy
Hyperplasia
Lactic Acid
Up-Regulation
Endothelial Cells
Immunohistochemistry

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

Energy substrate-supplemented resuscitation affects brain monocarboxylate transporter levels and gliosis in a rat model of hemorrhagic shock. / Lin, Tom; Koustova, Elena; Chen, Huazhen; Rhee, Peter M; Kirkpatrick, John; Alam, Hasan B.; Cone, John B.

In: Journal of Trauma, Vol. 59, No. 5, 11.2005, p. 1191-1202.

Research output: Contribution to journalArticle

Lin, Tom ; Koustova, Elena ; Chen, Huazhen ; Rhee, Peter M ; Kirkpatrick, John ; Alam, Hasan B. ; Cone, John B. / Energy substrate-supplemented resuscitation affects brain monocarboxylate transporter levels and gliosis in a rat model of hemorrhagic shock. In: Journal of Trauma. 2005 ; Vol. 59, No. 5. pp. 1191-1202.
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T1 - Energy substrate-supplemented resuscitation affects brain monocarboxylate transporter levels and gliosis in a rat model of hemorrhagic shock

AU - Lin, Tom

AU - Koustova, Elena

AU - Chen, Huazhen

AU - Rhee, Peter M

AU - Kirkpatrick, John

AU - Alam, Hasan B.

AU - Cone, John B.

PY - 2005/11

Y1 - 2005/11

N2 - 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.

AB - 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.

KW - Astrocytes

KW - GFAP

KW - GLUT1

KW - Hemorrhagic shock

KW - MCT1

KW - Microglia

KW - Monocarboxylates

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