Post-stroke Consequences Research Articles

Search for Stroke-Protecting Agents in Endothelin-1-Induced Ischemic Stroke Model in Rats

Ischemic stroke may initiate a reperfusion injury leading to brain damage cascades where inflammatory mechanisms play a major role. Therefore, the necessity for the novel stroke-protecting agents whose the mechanism of action is focused on their anti-inflammatory potency is still on the agenda for drug designers. Our previous studies demonstrated that cerebrocrast (a 1,4-dihydropyridine derivative) and mildronate (a representative of the aza-butyrobetaine class) possessed considerable anti-inflammatory and neuroprotective properties in different in vitro and in vivo model systems. The present study investigated their stroke-protecting ability in an endothelin-1 (ET-1)-induced ischemic stroke model in rats. Male Wistar rats were pretreated (for 7 days, per os) with cerebrocrast (0.1 mg/kg), mildronate (100 mg/kg), or their combination, followed by the intracerebral injection of ET-1. Functional and behavioral tests were carried out up to 14 days after the ET-1 injection. Ex vivo, the number of degenerated neurons and the infarction size in the cerebral cortical tissue were assessed histologically. Cerebrocrast and mildronate effectively normalized ET-1-induced disturbances in neurological status, improved the muscle tone, and decreased the number of degenerated cortical cells. Both drugs also reduced the infarction size, and cerebrocrast showed at least a 2-fold higher activity than mildronate. The combination of both drugs did not cause a more pronounced effect in comparison with the action of drugs administered separately. The 1,4-dihydropyridine and aza-butyrobetaine structures may serve for the design of novel stroke-protecting agents to prevent severe neurological poststroke consequences.

Patient preferences for stroke outcomes.

In clinical trials stroke is reported as a major morbid outcome, but the impact of stroke on patients is not directly assessed. This study examines patient preferences for different outcomes of stroke, including death. We presented patients with written case scenarios of stroke outcomes. The scenarios represented four categories of stroke severity (mild, moderate, severe, and fatal), and for nonfatal strokes the scenarios described motor, language, and cognitive deficits. Patients reported values for each of the 10 stroke scenarios using a rank-and-scale method over a 100-point range, with 100 representing perfect health and 0 corresponding to the worst possible health state. One hundred seventeen of 209 consecutive patients at risk for stroke participated in this study. Severe strokes were uniformly rated as having low preference weights (mean +/- SD [median]: 3 +/- 4 [1] for disabling hemiplegia, 8 +/- 9 [5] for confusion, and 15 +/- 14 [10] for global aphasia), and severe motor impairment (a disabling hemiplegia) was rated as significantly worse than death. Even mild deficits resulted in substantial loss to patients (54 +/- 21 [55] for dysarthria and 53 +/- 21 [50] for mild anomia). Strokes may result in a wide variety of post-stroke consequences for patients. Severe strokes may be viewed by patients as tantamount to or worse than death. Even mild strokes may cause significant declines in patient preferences for health states. These data are useful in interpreting studies that report stroke and death, in designing new studies that measure stroke in at-risk populations, and in helping patients reach treatment decisions about therapies designed to prevent strokes.