Neurone-specific enolase and N-acetyl-aspartate as potential peripheral markers of ischaemic stroke

After stroke, brain-specific proteins (including neurone-specific enolase) leak into the blood. The question addressed in the present study was whether N-acetyl-aspartate (amino acid derivative localized in cerebral neurones) could also serve as a peripheral marker of ischaemic damage. N-acetyl-aspartate levels were determined in the blood of stroke patients and related to clinical outcome, volume of infarction and to serum neurone-specific enolase.

Blood samples from 19 patients (seven women, 12 men, mean age of 73 years, range 56-88 years) were collected during the first 4 days after stroke and analysed for neurone-specific enolase (radioimmunoassay) and/or N-acetyl-aspartate (mass spectrometry). Clinical outcome was assessed using the Glasgow Outcome Score, and volume of infarction was calculated using computerized tomography (CT). Control values of N-acetyl-aspartate, determined in six female and nine male volunteers (mean age 47.4 years; range 28-73 years) were 0.26 +/- 0.02 mumol L-1.

The increase in serum N-acetyl-aspartate was highly significant (P < 0.0001) within the first 24 h and at 72 h after stroke and correlated (P < 0.05) with volume of infarction only in patients with a bad prognosis (Glasgow Outcome Score < 5). Serum N-acetyl-aspartate at 24 h and neurone-specific enolase at 72 h were negatively correlated, suggesting that more N-acetyl-aspartate reaches the blood when brain tissue is less irreversibly affected.

Serum N-acetyl-aspartate appears to be an early peripheral marker of ischaemically affected brain neurones, and the ratio of N-acetyl-aspartate to a protein marker, such as NSE, may serve as an index of irreversibility.