Energy Metabolism During Brain Ischemia• The permissible duration of brain ischemia without sustaining damage is short. Less clear are the mechanisms accounting for the vulnerability of brain to ischemic insults. Neurochemical factors implicated include impairment of energy synthesis by mitochondria and of energy-dependent processes such as synaptic transmission, ATPase activity, membrane conductance and altered protein and lipid synthesis. To clarify the vulnerability of energy metabolism, we investigated energy availability and synthesis in our model of global cerebral ischemia. Our studies evaluated in vitro mitochondrial ATP synthesis and the in vivo quantitation of the cortical adenylate pool. Results of our investigations support a growing body of evidence showing the energy state to be relatively stable to ischemia. We conclude that an energy-dependent process of brain is primarily vulnerable to ischemia. 5 Our investigations confirm and extend these observations by correlating simultaneous in vitro and in vivo parameters of energy metabolism with functional recovery. In our model of global ischemia, 6 ischemia was created by combining systemic hypotension with hypoxia of varying periods followed by circulatory restoration. Energy metabolism was evaluated with in vitro mitochondrial ATP synthesis and the in vivo cortical adenylate pool. Additional Key Methods BRAIN ISCHEMIA AND RECOVERYRandom-bred New Zealand white rabbits weighing between 4 and 5 kg were used. The rabbits were given a rapid-acting anesthesia, Ketamine (cyclohexylamine), intubated, and paralyzed with succinylcholine. Ventilation was performed mechanically with a Harvard pump. Two dural electrodes were implanted to record the electroencephalogram. The femoral artery was catheterized for constant blood pressure recording and the collection of blood for gases and pH measurements. A detailed description of procedures and the dosage of various pharmacological agents used have been

—Rat brain mitochondrial ATP synthesis was studied by measuring labeled orthophosphate incorporation into ADP to form ATP. GABA stimulates ATP synthesis, and this effect requires glutamate since with GABA alone little ATP is formed. The significance of this effect by GABA is unclear, but the mechanism may relate to induction of conformational change or chelation of cation.

No abstract

No abstract