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Signaling, delivery and age as emerging issues in the benefit/risk ratio outcome of tPA For treatment of CNS ischemic disorders
Author(s) -
Armstead William M.,
Ganguly Kumkum,
Kiessling J. W.,
Riley John,
Chen XiaoHan,
Smith Douglas H.,
Stein Sherman C.,
Higazi Abd A. R.,
Cines Douglas B.,
Bdeir Khalil,
Zaitsev Sergei,
Muzykantov Vladimir R.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06613.x
Subject(s) - medicine , tissue plasminogen activator , stroke (engine) , ischemia , context (archaeology) , neurovascular bundle , brain ischemia , intensive care medicine , pathology , mechanical engineering , paleontology , engineering , biology
J. Neurochem. (2010) 113 , 303–312. Abstract Stroke is a leading cause of morbidity and mortality. While tissue‐type plasminogen activator (tPA) remains the only FDA‐approved treatment for ischemic stroke, clinical use of tPA has been constrained to roughly 3% of eligible patients because of the danger of intracranial hemorrhage and a narrow 3 h time window for safe administration. Basic science studies indicate that tPA enhances excitotoxic neuronal cell death. In this review, the beneficial and deleterious effects of tPA in ischemic brain are discussed along with emphasis on development of new approaches toward treatment of patients with acute ischemic stroke. In particular, roles of tPA‐induced signaling and a novel delivery system for tPA administration based on tPA coupling to carrier red blood cells will be considered as therapeutic modalities for increasing tPA benefit/risk ratio. The concept of the neurovascular unit will be discussed in the context of dynamic relationships between tPA‐induced changes in cerebral hemodynamics and histopathologic outcome of CNS ischemia. Additionally, the role of age will be considered since thrombolytic therapy is being increasingly used in the pediatric population, but there are few basic science studies of CNS injury in pediatric animals.