Transient increase in CSF GAP-43 concentration after ischemic stroke

Background

Cerebrospinal fluid (CSF) biomarkers reflect ongoing processes in the brain. Growth-associated protein 43 (GAP-43) is highly upregulated in brain tissue shortly after experimental ischemia suggesting the CSF GAP-43 concentration may be altered in ischemic brain disorders. CSF GAP-43 concentration is elevated in Alzheimer’s disease patients; however, patients suffering from stroke have not been studied previously.

Methods

The concentration of GAP-43 was measured in longitudinal CSF samples from 28 stroke patients prospectively collected on days 0–1, 2–4, 7–9, 3?weeks, and 3–5?months after ischemia and cross-sectionally in 19 controls. The stroke patients were clinically evaluated using a stroke severity score system. The extent of the brain lesion, including injury size and degrees of white matter lesions and atrophy were evaluated by CT and magnetic resonance imaging.

Results

Increased GAP-43 concentration was detected from day 7–9 to 3?weeks after stroke, compared to day 1–4 and to levels in the control group (P?=?0.02 and P?=?0.007). At 3–5?months after stroke GAP-43 returned to admission levels. The initial increase in GAP-43 during the nine first days was associated to stroke severity, the degree of white matter lesions and atrophy and correlated positively with infarct size (r_s?=?0.65, P?=?0.001).

Conclusions

The transient increase of CSF GAP-43 is important to take into account when used as a biomarker for other neurodegenerative diseases such as Alzheimer’s disease. Furthermore, GAP-43 may be a marker of neuronal responses after stroke and additional studies confirming the potential of CSF GAP-43 to reflect severity and outcome of stroke in larger cohorts are warranted.