When a person experiences brain trauma, also called as concussion, the body respond accordingly. Concussion leads to the disruption of amino acids concentrations in the brain, which is the source of behavioral and neurological symptoms experienced later on. The amino acids are also known as the building blocks of proteins. Glutamate, the main excitatory amino acid in the brain, plays an important role in the mechanics of this disruption.
Goal
Right after a brain concussion, there is a massive release of glutamate from the brain cells, exacerbating the damage caused by the injury. Glutamate overactivates N-methyl-D-aspartate, which plays an important role in memory, among other things. The purpose of this study was to evaluate the efficacy of N-methyl-D-aspartate receptor blocker MK-801 on glutamate and other amino acid levels following concussion in rats.
methodology
As the disruption of amino acid concentrations in the brain cannot be characterized in humans, a rat model of concussion was developed that closely mimics the biomechanics of this type of injury. To do this, cerebral microdialysis was applied. This technique allows to measure amino acids such as glutamate, in the awake rat, before, during and after a concussion. The cerebral microdialysis is performed by inserting a tube in the brain, which contains a membrane that is semi-permeable to water and small molecules, allowing the collection of a liquid that is representative of the environment outside of the cells. A dose of MK-801 medication was injected as therapy (immediately after the concussion) or as prevention (1 hour before the concussion).
main findings
The glutamate and other amino acids concentrations following concussion were similar in rats given a dose of MK-801 in therapy and those given only a dose of placebo (having no efficacy on its own). In contrast, amino acids concentrations following concussion in rats that were given the drug as a preventive measure remained comparable to the rats without injury.
take home message
Despite the demonstrated efficacy of MK-801 when it’s given as a preventive measure, the administration of a N-methyl-D-aspartate blocker (such as MK-801) prior to intense physical activities such as football or hockey could significantly interfere with athletes’ performance. However, regardless of previous failures in the mode of administration in therapy, this type of drug could be very beneficial for concussed athletes. The next step is to develop an alternative treatment with faster drug delivery.
