title: Reduced cerebral monocarboxylate transporters and lactate levels by ethanol and normobaric oxygen therapy in severe transient and permanent ischemic stroke.
abstract: OBJECTIVE
  Neuroprotective benefits of ethanol (EtOH) and normobaric oxygenation (NBO) were previously demonstrated in transient and permanent ischemic stroke. Here we sought to identify whether the enhanced lactic acidosis and increased expression of monocarboxylate transporters (MCTs) observed after stroke might be attenuated by single and/or combined EtOH and NBO therapies.
  
  
  METHODS
  Sprague-Dawley rats (n=96) were subjected to right middle cerebral artery occlusion (MCAO) for 2 or 4h (transient ischemia), or 28 h (permanent ischemia) followed by 3, 24h, or no reperfusion. Rats received: (1) either an intraperitoneal injection of saline (sham treatment), one dose of EtOH (1.5 g/kg), two doses of EtOH (1.5 g/kg at 2h of MCAO, followed by 1.0 g/kg 2h after 1st dose), or (2) EtOH+95% NBO (at 2h of MCAO for 6h in permanent ischemia). Lactate levels were detected at 3 and 24h of reperfusion. Gene and protein expressions of MCT-1, -2, -4 were assessed by real-time PCR and western blotting.
  
  
  RESULTS
  A dose-dependent EtOH neuroprotection was found in transient ischemia. Following transient ischemia, a single dose of EtOH (in 2h-MCAO) or a double dose (in 4h-MCAO), significantly attenuated lactate levels, as well as the mRNAs and protein expressions of MCT-1, MCT-2, and MCT-4. However, while two doses of EtOH alone was ineffective in permanent stroke, the combined therapy (EtOH+95% NBO) resulted in a more significant attenuation in all the above levels and expressions.
  
  
  CONCLUSIONS
  Our study demonstrates that acute EtOH administration attenuated lactic acidosis in transient or permanent ischemic stroke. This EtOH-induced beneficial effect was potentiated by NBO therapy in permanent ischemia. Because both EtOH and NBO are readily available, inexpensive and easy to administer, their combination could be implemented in the clinics shortly after stroke.
authors: China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China; Department of Neurological Surgery, Wayne State University School of Medicine, 550 E Canfield, Detroit, MI 48201, USA.
authors: Xiaokun
authors: X
authors: Geng
authors: Department of Neurological Surgery, Wayne State University School of Medicine, 550 E Canfield, Detroit, MI 48201, USA.
authors: Christopher A
authors: CA
authors: Sy
authors: Department of Neurological Surgery, Wayne State University School of Medicine, 550 E Canfield, Detroit, MI 48201, USA.
authors: Timothy D
authors: TD
authors: Kwiecien
authors: China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Xuanwu Hospital, China-America Institute of Neuroscience, Luhe Hospital Capital Medical University, Beijing 100053, China. Electronic address: jixm@ccmu.edu.cn.
authors: Xunming
authors: X
authors: Ji
authors: Department of Neurological Surgery, Wayne State University School of Medicine, 550 E Canfield, Detroit, MI 48201, USA.
authors: Changya
authors: C
authors: Peng
authors: Department of Neurological Surgery, Wayne State University School of Medicine, 550 E Canfield, Detroit, MI 48201, USA.
authors: Radhika
authors: R
authors: Rastogi
authors: China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China; Department of Neurological Surgery, Wayne State University School of Medicine, 550 E Canfield, Detroit, MI 48201, USA.
authors: Lipeng
authors: L
authors: Cai
authors: China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China.
authors: Huishan
authors: H
authors: Du
authors: Department of Neurological Surgery, Wayne State University School of Medicine, 550 E Canfield, Detroit, MI 48201, USA.
authors: David
authors: D
authors: Brogan
authors: Department of Neurological Surgery, Wayne State University School of Medicine, 550 E Canfield, Detroit, MI 48201, USA.
authors: Sunpreet
authors: S
authors: Singh
authors: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, USA.
authors: Jose A
authors: JA
authors: Rafols
authors: China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China; Department of Neurological Surgery, Wayne State University School of Medicine, 550 E Canfield, Detroit, MI 48201, USA. Electronic address: yding@med.wayne.edu.
authors: Yuchuan
authors: Y
authors: Ding
mesh_terms: D000140:Acidosis, Lactic / Q000378:metabolism / Q000628:therapy; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010102:Oxygen Inhalation Therapy / Q000379:methods*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism / Q000628:therapy*; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000431:Ethanol; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D018696:Neuroprotective Agents; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C516342:Slc16a3 protein, rat; C091633:Slc16a7 protein, rat
keywords: EtOH; Ischemia/reperfusion injury; Lactic acidosis; MCT; NBO; Neuroprotection; Stroke