Abstract
The clinical course after ischemic stroke can vary considerably despite similar lesions and clinical status at the onset of symptoms, suggesting that individual factors modulate clinical recovery. Here, we sought to test the working hypothesis that elevated copper values provide prognostic information, and specifically predict worse clinical recovery. We further sought to support previous findings regarding metal metabolism in acute stroke. We assessed total antioxidant status, oxidative stress factors (peroxides) and metal metabolism markers (iron, copper, ceruloplasmin concentration and activity, ferritin, and transferrin) in the acute phase (2–10 days from symptom onset) in 30 patients affected by unilateral middle cerebral artery (MCA) stroke. A longitudinal assessment of clinical deficit was performed in the acute and stabilized phases (typically 6 months post-stroke) using the National Institutes of Health Stroke Scale (NIHSS). In identifying recovery-related factors, we considered effective recovery (ER), calculated as the ratio between actual NIHSS recovery and the total potential recovery. This allows an estimation of the actual recovery adjusted for the patient’s initial condition. In the acute phase, clinical severity was correlated with increased peroxide concentrations, and lower iron levels. Less successful clinical recovery was correlated with increased acute copper levels, which entered a multiple regression model that explained 24% of ER variance. These pilot data suggest that, in the acute phase of an ischemic stroke, copper may provide useful information about clinical recovery.
Highlights
Ischemic stroke is the rapid loss of brain function due to a reduction in the blood supply to the brain
In accordance with the normalization introduced in the effective recovery (ER) definition to study the recovery abilities “independently of ” the acute phase clinical state, the National Institutes of Health Stroke Scale (NIHSS) at t0 did not display a significant correlation with the ER
The main result of our study is that elevation of serum copper measured in the acute phase provided information about a less successful clinical recovery after ischemic stroke, as assessed through the ER index
Summary
Ischemic stroke is the rapid loss of brain function due to a reduction in the blood supply to the brain. Three previous studies discovered significantly elevated contents of both total copper and “free” copper (generally understood as copper not bound to ceruloplasmin, nCp-Cu) in the serum of cerebral ischemic stroke patients [10, 13, 14], while others described the direct role of copper in learning and memory tied to plasticity mechanisms largely mediated by glutamate neurotransmission [7, 15,16,17]. In both healthy people and Alzheimer’s disease patients, we observed a link between circulating copper and glutamate-mediated neural transmission [18, 19]. Our secondary aim was to confirm previous results about iron, copper, ceruloplasmin, ferritin, and Tf trends in the ischemic acute phase
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