The effects of dietary sulfur amino acid deficiency on rat brain glutathione concentration and neural damage in global hemispheric hypoxia-ischemia.
Primary brain injury in stroke is followed by an excitotoxic cascade, oxidative stress and further neural damage. Glutathione is critical and depleted in oxidative stress. Since cysteine is limiting in glutathione synthesis, this study investigated the effect of dietary sulfur amino acid (SAA) deficiency on neural damage in a rat model of global hemispheric hypoxia-ischemia (GHHI). Animals were fed with SAA deficient ("deficient") or control diet for 3 days, subjected to right common carotid artery ligation and hypoxia, and diet continued for 3 more days. Histologically evaluated neural damage at 7 days post hypoxia-ischemia was greater in "deficient" rats, shown by mean (+/- SEM) global and hippocampal grid scores of 2.5 +/- 0.7 and 34.9 +/- 9.3%, respectively, vs. controls' scores of 0.1 +/- 0.1 and 0.1 +/- 0.1%, respectively. Mean brain (+/- SEM) reduced glutathione was not different between groups at 6h post hypoxia-ischemia, but was decreased in "deficient" animals 3 days later in neocortex (1.46 micromoles/g wet weight +/- 0.05 vs. 1.67 +/- 0.04 in controls) and thalamus (1.60 micromoles/g wet weight +/- 0.05 vs. 1.78 +/- 0.03 in controls). Administration of a cysteine precursor to "deficient" animals did not ameliorate neural damage. These findings suggest that well-nourished but not "deficient" animals tolerate a mild brain insult. The decline in brain glutathione in the "deficient" animals may be one of several contributing mechanisms.
Bobyn
P Joan
PJ
College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Sask., S7N 5C9, Canada.
Franklin
Jodi L
JL
Wall
Cindy M
CM
Thornhill
James A
JA
Juurlink
Bernhard H J
BH
Paterson
Phyllis G
PG
D000603:Amino Acids, Sulfur / Q000008:administration & dosage / Q000172:deficiency*; D000818:Animals; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D003342:Corpus Striatum / Q000473:pathology; D004032:Diet; D005978:Glutathione / Q000032:analysis*; D006624:Hippocampus / Q000737:chemistry / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D019579:Neocortex / Q000737:chemistry / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D013788:Thalamus / Q000737:chemistry
D000603:Amino Acids, Sulfur; D008869:Microtubule-Associated Proteins; D005978:Glutathione