From the Acute Stroke Unit, University Department of Medicine and
Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, Scotland.
Correspondence to Dr A.G. Dyker, Acute Stroke Unit, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK. E-mail AD47Q{at}clinmed.gla.ac.uk
Background—The therapeutic time
window for thrombolysis appears to be extremely short,
probably because of the hemorrhagic complications associated with late
reperfusion of ischemic brain tissue. Other neuroprotective
forms of treatment continue to be developed, although their efficacy
has yet to be conclusively proved in patients. The duration of
treatment in recent phase 3 trials ranges from a single bolus injection
to 12 weeks of oral therapy.
Summary of Review—In this article we discuss the factors that
should influence the choice of route and duration of treatment.
Excitotoxic injury following stroke evolves over at least 4 hours in
rodents and possibly beyond 48 hours in humans. In addition,
autoregulation and local cerebral perfusion are deranged for
approximately 72 hours in patients with stroke. Neuroprotection should
provide cover during this critical time.
Conclusions—Important considerations influencing drug
administration should include the pharmacology of the compound
(pharmacokinetics, mechanism of action, preclinical toxicity, and
pharmaceutical properties), its safety and tolerability in patients,
and the likelihood of continuing or recurrent cerebral
ischemia, along with practical issues such as ease of
administration and interactions with early rehabilitation and other
therapies. Optimization of treatment will be possible only when
neuroprotection is confirmed to be effective.
© 1998 American Heart Association, Inc.
Comments, Opinions, and Reviews
Duration of Neuroprotective Treatment for Ischemic Stroke
Key Words: cerebral ischemia • neuroprotection • glutamates • N-methyl-D-aspartate • drug therapy • penumbra
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