In patients with moderate traumatic brain injury (TBI), memantine, an N-methyl-D-aspartate (NMDA) receptor modulator, has been shown to reduce blood levels of neuron-specific enolase (NSE), a biomarker of brain damage. Findings from the trial were published in The Journal of Clinical Pharmacology.

The study, conducted by researchers from the University of Medical Sciences in Tehran, Iran, is the first to test memantine in this patient population.

Memantine is FDA approved to treat moderate-to-severe dementia associated with Alzheimer’s disease. In TBI, delayed complex molecular and cellular pathophysiological changes as a result of a primary injury (direct physical tissue disruption) may be potentially preventable or even reversible.

The researchers enrolled 41 patients suffering from moderate TBI with a Glasgow Coma Score (GCS) of 9–12. Nineteen patients were randomly assigned to the control group (receiving standard TBI management) and 22 patients were assigned to the treatment group (receiving standard management and enteral memantine 30mg twice daily for 7 days). 

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NSE serum levels are a reliable laboratory indicator for the degree of brain cell damage. These scores were assessed before and after treatment. Before study initiation, NSE levels were similar for both groups. On Day 3 of the study, the NSE levels were 7.95 ± 2.86 ng/mL for the memantine group and 12.33 ± 7.09 ng/mL for the control group (P=0.05).

From baseline to Day 7, the percentage reduction in serum NSE levels were statistically significant: 74.2% ± 14.9% and 48.7% ± 29.1% in the memantine and the control groups, respectively (P=0.009). Day-to-day improvements in GCS were also recorded in the memantine group.

Previous research has demonstrated how memantine is able to protect dissociated cortical neurons from glutamate-induced excitotoxicity, the authors point to this as a possible mechanism for neuronal protection in TBI.

They concluded that, “memantine started quickly” after a TBI can significantly reduce neuronal damage as assessed by the NSE biomarker. However, they write that, “larger multicenter trials with prolonged outcome assessments are needed to validate our findings.”

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