Energy metabolism and cerebral blood flow during cytotoxic brain edema induced by 6-aminonicotinamide.
We investigated the progression of cytotoxic brain edema induced by 6-aminonicotinamide (6-ANA), a potent antimetabolite of nicotinamide, by measuring the time courses of changes in brain tissue water state (with MRI), histology (with H&E staining), energy metabolism (with 31P-NMR), brain hemoglobin concentration (with near-infrared spectroscopy; NIRS), cerebral blood flow and volume (CBF. CBV), mean arterial blood pressure (MABP), and brain activity (with EEG) up to 10 hours (h). Change in cerebrovascular autoregulation was also investigated. 6-ANA (120 mg/kg) was administered intraperitoneally to 30 male Wistar rats (250-350 g). After 10 h, the T2-weighted signal intensity was increased (p < 0.05), and H&E staining showed severe vacuolation of glial cells. ATP production/consumption and intracellular pH were well maintained up to 10 h, while the intensity of the phosphomonoesters (PME) signal was significantly increased (p < 0.05). Oxygen consumption gradually decreased from 4 to 10 h. CBF and MABP were all significantly increased (by 2.5-fold for CBF) (p < 0.05). Theta and delta wave amplitudes were reduced at 10 h. In summary, 6-ANA (120 mg/kg) induced cytotoxic brain edema from 4 to 10 h. Energy balance and brain activity were well maintained up to 10 h, though cerebrovascular autoregulation was impaired.
Kurita
D
D
Department of Neurology, Tokai University School of Medicine, Kanagawa, Japan. kurita@is.icc.u-tokai.ac.jp
Haida
M
M
Shinohara
Y
Y
D015120:6-Aminonicotinamide; D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004569:Electroencephalography; D004734:Energy Metabolism; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006454:Hemoglobins; D015120:6-Aminonicotinamide