It is well known that abnormally elevated
glutamate levels in the brain are associated with secondary
brain injury following acute and chronic brain insults. As such, a tight regulation of brain
glutamate concentrations is of utmost importance in preventing the neurodegenerative effects of excess
glutamate. There has been much effort in recent years to better understand the mechanisms by which
glutamate is reduced in the brain to non-toxic concentrations, and in how to safely accelerate these mechanisms. Blood
glutamate scavengers such as
oxaloacetate,
pyruvate,
glutamate-
oxaloacetate transaminase, and
glutamate-
pyruvate transaminase have been shown to reduce blood
glutamate concentrations, thereby increasing the driving force of the brain to blood
glutamate efflux and subsequently reducing brain
glutamate levels. In the past decade, blood
glutamate scavengers have gained increasing international interest, and its uses have been applied to a wide range of experimental contexts in animal models of
traumatic brain injury,
ischemic stroke,
subarachnoid hemorrhage,
epilepsy,
migraine, and
malignant gliomas. Although
glutamate scavengers have not yet been used in humans, there is increasing evidence that their use may provide effective and exciting new therapeutic modalities. Here, we review the laboratory evidence for the use of blood
glutamate scavengers. Other experimental neuroprotective treatments thought to scavenge blood
glutamate, including
estrogen and
progesterone, beta-
adrenergic activation,
hypothermia,
insulin and
glucagon, and
hemodialysis and
peritoneal dialysis are also discussed. The evidence reviewed here will hopefully pave the way for future clinical trials.