, Volume 258, Issue 10, pp 1885-1887
Date: 13 Apr 2011

No evidence for an association between genetic variation at the SERPINI1 locus and ischemic stroke

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Dear Sirs,

Neuroserpin, primarily expressed by neurons, is an important inhibitor of tissue-type plasminogen activator (t-PA). t-PA has a multifaceted role in the brain and is involved in several physiologic and pathologic processes. Its beneficial role on the vascular side is attributed to its thrombolytic function. Moreover, recombinant t-PA is the only FDA-approved pharmacological treatment of acute ischemic stroke (IS) [1]. In the brain there are several cell-types that express t-PA besides the cerebrovascular endothelial cells, e.g. neurons, microglia and astrocytes [2]. Under physiological conditions t-PA is involved in synaptic plasticity and memory-related processes [3, 4]. However, during pathological conditions, such as in the acute phase of IS, excess release of t-PA may trigger proteolytic cascades, subsequently leading to excitotoxicity and neurodegeneration [5, 6]. In this context, t-PA has been associated with increased stroke volume [7] and increased cerebrovascular perm