?Cerebral? lactic acidosis: defects in pyruvate metabolism with profound brain damage and minimal systemic acidosis

AbstractPrimary lactic acidemias represent a family of disorders of pyruvate metabolism or defects in the respiratory chain. However, lactic acidosis may also be seen in metabolic disorders such as organic acidemias, urea cycle defects, and fatty acid oxidation defects, which can be easily excluded by serum ammonia estimation, urinary organic acid estimation, and quantification of plasma amino acids. The classical presentation of a patient with primary lactic acidemia is growth retardation, ataxia, stroke, and increased lactic acid levels in the blood and cerebrospinal fluid. Patients may also present with cerebral edema, acute rhabdomyolysis, cardiac arrhythmias, cardiomyopathy, coma, and neurodegeneration. We present three cases of lactic acidemia with varied presentation. The first child presented at 5 years with recurrent hematemesis with hypoglycemia. The second child presented at 11 years of age with recurrent episodes of unconsciousness. The third child presented at one and a half months with convulsions.

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A case of abnormal pyruvate metabolism leading to intractable lactic acidosis, in which blood purification provided a useful treatment option

Journal of the Japanese Society of Intensive Care Medicine ◽

10.3918/jsicm.21.165 ◽

2014 ◽

Vol 21 (2) ◽

pp. 165-168

Author(s):

Kotaro Hori ◽

Kenta Takeda ◽

Takeshi Ide ◽

Shinichi Nishi

Keyword(s):

Lactic Acidosis ◽

Treatment Option ◽

Blood Purification ◽

Pyruvate Metabolism

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Abstract T P96: Controlled Brain Glucose Uptake and Metabolism by Ethanol: An Alternative Approach in Improving Stroke Outcome

Stroke ◽

10.1161/str.46.suppl_1.tp96 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Fauzia Akbary ◽

Changya Peng ◽

Karam Asmaro ◽

Ryan Kochanski ◽

Murali Guthikonda ◽

...

Keyword(s):

Blood Glucose ◽

Brain Injury ◽

Lactic Acidosis ◽

Atpase Activity ◽

Glucose Uptake ◽

Brain Damage ◽

Brain Glucose ◽

Glut 1 ◽

Glucose Levels ◽

Uptake And Metabolism

Introduction: Post-stroke oxygen deficit impairs oxidative phosphorylation of glucose. Surviving brain cells increase anaerobic glycolysis (hyperglycolysis) promoting reactive oxygen species (ROS) synthesis via lactic acidosis and NADPH oxidase (NOX) activation. Hyperglycemia present in 40% of stroke patients with or without diabetes perpetuates hyperglycolysis. Insulin, the only treatment to attenuate hyperglycemia-induced hyperglycolysis, is linked to increased risk of hypoglycemia and mortality. We showed that EtOH reduced ROS-mediated brain damage. Here, we studied whether hyperglycemia/hyperglycolysis-enhanced brain injury are ameliorated by reducing brain glucose uptake and metabolism rather than affecting blood glucose levels. Methods: Sprague-Dawley rats underwent a 2 h right middle cerebral artery occlusion (MCAO). EtOH (1.5 g/kg) or saline was injected IP upon reperfusion, then sacrificed 3 and 24 h later. Energy stores, hyperglycolysis-associated glucose uptake and metabolism, lactic acidosis, and oxidative stress were assessed via ADP/ATP ratio, NAD+/NADH ratio, Na+/K+ ATPase activity, levels of brain and blood glucose, glucose transporter GLUT 1 and 3, lactate, lactate dehydrogenase (LDH), ROS, phosphofructokinase-1 (PFK-1), NOX, and PFK-1 and NOX activity. Results: Ischemic rats showed significant (p<0.01) increase in ADP/ATP and NAD+/NADH ratios, and decrease in Na+/K+ ATPase activity indicating impaired metabolic and neural activity. Increased blood glucose and decreased brain glucose indicate hyperglycemic condition with hyperglycolysis. High levels of GLUT 1 and 3, lactate, LDH , PFK-1, NOX, and ROS support ROS associated hyperglycolysis. EtOH normalized these metabolic parameters to control levels, but only blood glucose remained higher. In sum, EtOH attenuates hyperglycemia-enhance brain injury by reducing glucose uptake and its hyperglycolytic-mediated metabolism under hyperglycemic condition. Conclusion: EtOH administered upon reperfusion is neuroprotective against ROS-mediated brain damage in acute ischemic stroke. It attenuates hyperglycemia-enhanced hyperglycolysis at the level of glucose uptake, utilization, and metabolism rather than reducing serum glucose levels.

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