Malonate is regarded as a reversible competitive inhibitor of succinate dehydrogenase and malate transport in the Krebs cycle and showed neurotoxicity by persistent NMDA receptor activation due to inhibition of ATP production and glutamate utilization. However, little was known about its biological effects and the range of normal concentration of malonate in central nervous system. In order to understand the relationship between malonate and vasospsasm, malonate concentrations in rabbit model of experimental subarachnoid hemorrhage were measured at 0, 4th, and 7th day following SAH in serum, cerebrospinal fluid, and urine using malonyl-CoA synthetase. The results were as follows: 1) Malonate level is increased significantly in serum at the 4th day after subarachnoid hemorrhage that followed by vasospasm(p<0.01). 2) CSF malonate concentration tends to increase at post-SAH 7th day but statistically not significant. 3) The change of urine malonate concentration is not significant. These results suggest that early increase of serum malonate level is significant because clinically important vasospam begin from the fourth through the seventh day after hemorrhage. The increased level of serum malonate at this time is due to impairment of cellular metabolism following delayed cerebral ischemia and may influence to development of vasospasm. In conclusion, the measurement of serum malonate concentration after subarachnoid hemorrhage is one of possible candidates for the early diagnosis of vasospasm.
Adenosine Triphosphate ; Brain Ischemia ; Central Nervous System ; Cerebrospinal Fluid ; Citric Acid Cycle ; Early Diagnosis ; Glutamic Acid ; Hemorrhage ; Ligases ; Metabolism ; N-Methylaspartate ; Subarachnoid Hemorrhage ; Succinate Dehydrogenase