Correlation between lactate and neuronal cell damage in the rat brain after focal ischemia: An in vivo 1H magnetic resonance spectroscopic (1H-MRS) study.
BACKGROUND
Increased levels of lactate are observed by (1)H magnetic resonance spectroscopy ((1)H-MRS) in rat brains after stroke. However, it is not known whether the changes in lactate levels are predictive of the degree of neuronal damage.


OBJECTIVE
To investigate the correlation between changes in lactate and lipid levels measured by (1)H-MRS and neuronal cell damage in the rat brain.


METHODS
A middle cerebral artery occlusion (MCAO) model was used to evaluate focal ischemia in rats (n=36). After MCAO for 90 min T2-weighted images (T2WIs), diffusion-weighted images (DWIs), and (1)H-MRS data were obtained from brains immediately, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, 3 days, and 7 days after reperfusion. Infarct volumes were measured in T2WIs obtained 4 weeks after reperfusion. The degree of neuronal damage was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining in three rats from each group at the same time as brain images were collected.


RESULTS
Creatine (Cr)-normalized lactate + lipid levels ([Lac+Lip]/Cr) were negatively correlated with Cr-normalized N-acetyl-L-aspartate levels (NAA/Cr) and positively correlated with TUNEL-positive cell numbers up to 24 hours after reperfusion. (Lac+Lip)/Cr at 6 hours and 9 hours was significantly correlated with NAA/Cr at 7 days, but there was no significant correlation between (Lac+Lip)/Cr during the first 24 hours and infarct volume at 4 weeks.


CONCLUSIONS
Up to 24 hours after reperfusion, (Lac+Lip)/Cr was strongly negatively correlated with NAA/Cr, and was a good predictor of neuronal damage at 7 days; however, it was not predictive of final infarct volume at 4 weeks.
Asan Institute for Life Science, Asan Medical Center, Songpa-gu, Seoul, Republic of Korea.
Chul-Woong
CW
Woo
Byong Sop
BS
Lee
Sang Tae
ST
Kim
Ki-Soo
KS
Kim
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D003404:Creatinine / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D020287:In Situ Nick-End Labeling / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D019344:Lactic Acid / Q000378:metabolism*; D050356:Lipid Metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D003404:Creatinine