Markers of Excitotoxicity in Patients: Tool for Diagnosis or Therapy?

The role of excitotoxicity in single patients affected by neurological disorders is difficult to assess, but it may provide useful indications as far as prognosis and response to therapy. Glutamate levels could be measured in biological fluids, such as plasma and cerebrospinal fluid. Increased levels of the amino acid have been demonstrated in cerebrovascular diseases, amyotrophic lateral sclerosis (ALS) and AIDS dementia complex (ADC). In the case of stroke and ADC, glutamate levels correlated with disease severity. Molecular and biochemical markers of glutamatergic transmission can be assessed in peripheral tissues, such as platelets and fibroblasts, which physiologically express the three major glutamate transporters. Expression of EAAT1 (GLAST) glutamate transporter was reported to be reduced in platelets and fibroblasts from Alzheimer’s disease (AD) patients. Functional glutamate uptake studies showed a reduced Vmax in platelets from patients with AD, Down syndrome (DS), Parkinson’s disease (PD), ALS and stroke. Fibroblasts from AD showed both reduced Vmax and altered regulatory responses. A number of systemic factors, such as genetics, oxidative stress and inflammatory mediators, may be responsible for the observed glutamate uptake impairment in neurological patients.