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

• 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 beta-hydroxybutyrate 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 beta-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.
• Authors: Tom Lin, Elena Koustova, Huazhen Chen, Peter M Rhee, John Kirkpatrick, Hasan B Alam (Affiliation: Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.)
• Journal: The Journal of trauma (J Trauma) Vol. 59 Issue 5 Pg. 1191-202; discussion 1202 (Nov 2005) ISSN: 0022-5282 [Print] United States
• PMID: 16385299 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antigens, CD11b
• Antigens, CD43
• Excitatory Amino Acid Transporter 2
• Glucose Transporter Type 3
• Isotonic Solutions
• Monocarboxylic Acid Transporters
• Ringer's ethyl pyruvate
• Slc2a3 protein, rat
• Symporters
• monocarboxylate transport protein 1
• Ringer's lactate

Topics

• Animals
• Antigens, CD11b (metabolism)
• Antigens, CD43 (metabolism)
• Brain (metabolism)
• Disease Models, Animal
• Excitatory Amino Acid Transporter 2 (metabolism)
• Gliosis (blood, physiopathology)
• Glucose Transporter Type 3 (metabolism)
• Immunohistochemistry
• Isotonic Solutions
• Male
• Monocarboxylic Acid Transporters (metabolism)
• Rats
• Rats, Sprague-Dawley
• Resuscitation
• Shock, Hemorrhagic (blood)
• Symporters (metabolism)
• Up-Regulation (physiology)