CEREBRAL OXIDATIVE-METABOLISM AND REDOX STATE DURING HYPOXIA-ISCHEMIA AND EARLY RECOVERY IN IMMATURE RATS

被引:64
作者
YAGER, JY [1 ]
BRUCKLACHER, RM [1 ]
VANNUCCI, RC [1 ]
机构
[1] PENN STATE UNIV, MILTON S HERSHEY MED CTR, DEPT PEDIAT PEDIAT NEUROL, HERSHEY, PA 17033 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1991年 / 261卷 / 04期
关键词
BRAIN; PERINATAL; GLUCOSE; PYRUVATE; ALPHA-KETOGLUTARATE;
D O I
10.1152/ajpheart.1991.261.4.H1102
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Intracellular pH (pH(i)) and cytoplasmic and mitochondrial oxidation-reduction (redox) states of cerebral tissue were examined in relation to perturbations of glycolytic and tricarboxylic acid cycle intermediates and of high-energy phosphate reserves during hypoxia-ischemia and the early recovery period in the immature rat. Seven-day postnatal rats underwent unilateral common carotid artery ligation and exposure to 8% O2 for 3 h, after which they were quick frozen in liquid N2 at the terminus of hypoxia-ischemia and at 10, 30, 60, and 240 min of recovery for enzymatic fluorometric analysis of cerebral metabolites. During hypoxia-ischemia, concentrations of glucose and alpha-ketoglutarate in the cerebral hemisphere ipsilateral to the carotid artery occlusion were depleted to 10 and 70% of control, respectively; pyruvate was unchanged. During recovery, glucose, pyruvate, and alpha-ketoglutarate increased above their respective control values. Calculated pH(i) decreased from 7.0 (control) to 6.6 during hypoxia-ischemia and normalized by 10 min of recovery. The cytoplasmic NAD+/NADH ratio decreased (increased reduction) to 50% of control during hypoxia-ischemia and remained in the reduced state throughout 4 h of recovery. Paradoxically, mitochondrial NAD+/NADH was oxidized at the terminus of hypoxia-ischemia. The mitochondrial oxidation which developed during hypoxia-ischemia presumably results from a limitation of cellular substrate (glucose) supply, which in turn leads to a depletion of high-energy phosphate reserves, culminating in brain damage.
引用
收藏
页码:H1102 / H1108
页数:7
相关论文
共 51 条
[1]   REGULATION OF OXIDATIVE-PHOSPHORYLATION IN THE MAMMALIAN-CELL [J].
BALABAN, RS .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (03) :C377-C389
[2]   CEREBRAL METABOLIC AND CIRCULATORY CHANGES INDUCED BY HYPOXIA IN STARVED RATS [J].
BERNTMAN, L ;
SIESJO, BK .
JOURNAL OF NEUROCHEMISTRY, 1978, 31 (05) :1265-1276
[3]  
Brown A W, 1977, J Clin Pathol Suppl (R Coll Pathol), V11, P155
[4]   INSUFFICIENT SUPPLY OF REDUCING EQUIVALENTS TO THE RESPIRATORY-CHAIN IN CEREBRAL-CORTEX DURING SEVERE INSULIN-INDUCED HYPOGLYCEMIA IN CATS [J].
BRYAN, RM ;
JOBSIS, FF .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1986, 6 (03) :286-291
[5]   PYRUVATE-DEHYDROGENASE ACTIVITY IN THE RAT CEREBRAL-CORTEX FOLLOWING CEREBRAL-ISCHEMIA [J].
CARDELL, M ;
KOIDE, T ;
WIELOCH, T .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1989, 9 (03) :350-357
[6]  
CHANCE B, 1955, J BIOL CHEM, V217, P383
[7]   RELATIONSHIP BETWEEN PLASMA-GLUCOSE, BRAIN LACTATE, AND INTRACELLULAR PH DURING CEREBRAL-ISCHEMIA IN GERBILS [J].
COMBS, DJ ;
DEMPSEY, RJ ;
MALEY, M ;
DONALDSON, D ;
SMITH, C .
STROKE, 1990, 21 (06) :936-942
[8]   KINETICS OF BLOOD-BRAIN-BARRIER TRANSPORT OF PYRUVATE, LACTATE AND GLUCOSE IN SUCKLING, WEANLING AND ADULT-RATS [J].
CREMER, JE ;
CUNNINGHAM, VJ ;
PARDRIDGE, WM ;
BRAUN, LD ;
OLDENDORF, WH .
JOURNAL OF NEUROCHEMISTRY, 1979, 33 (02) :439-445
[9]   DISPARATE RECOVERY OF RESTING AND STIMULATED OXIDATIVE-METABOLISM FOLLOWING TRANSIENT ISCHEMIA [J].
DUCKROW, RB ;
LAMANNA, JS ;
ROSENTHAL, M .
STROKE, 1981, 12 (05) :677-686
[10]   CEREBRAL ENERGY METABOLISM DURING EXPERIMENTAL STATUS EPILEPTICUS [J].
DUFFY, TE ;
HOWSE, DC ;
PLUM, F .
JOURNAL OF NEUROCHEMISTRY, 1975, 24 (05) :925-934