Duration of Neuroprotective Treatment for Ischemic Stroke

Abstract

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. (Stroke. 1998;29:535-542.)

Factors Associated with Prehospital Delay for Acute Stroke in Ulsan, Korea

“…However, most patients do not receive it: in one study, 30 (11.2%) of 267 patients had thrombolytic therapy, and only about 30% of acute stroke patients arrived within 2 h to receive thrombolytic therapy despite the known effectiveness of thrombolytics (7,8). Intravenous thrombolytic therapy is not recommended beyond its therapeutic time window due to the high risk of complications such as cerebral hemorrhage and poor neurological outcomes, leading to high medical costs and socioeconomic problems (3,9). Early hospital arrival is an important goal for acute thrombolytic therapy.…”

Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat

“…Among the initial events in the ischemic cascade are the widespread neuronal depolarization and massive release of glutamate (excitotoxicity) leading to calcium influx. Approaches focusing on blocking presynaptic glutamate release, ionotropic glutamate receptors, or voltage-sensitive calcium or sodium channels have so far failed to demonstrate a proven clinical efficacy [18,23,30].…”

Huanglian-Jie-Du-Tang Extract Protects against Chronic Brain Injury after Focal Cerebral Ischemia via Hypoxia-Inducible-Factor-1α-Regulated Vascular Endothelial Growth Factor Signaling in Mice

“…27) In the clinic, drug administration is highly variable, ranging from single to multiple doses for up to 3 months. 28) To treat chronic cerebral ischemia, a single dose may not provide enough protection, so prolonged administration is necessary. If the dose-effect characteristics of drugs show a bell-type dose-response relation, prolonged administration of the larger doses of HJDTet can have deleterious side effects or reduce therapeutic efficacy.…”