Influence of a ‘Brain Protector’ drug 21-amino steroid on the effects of experimental embolic stroke treated by thrombolysis

Abstract

This study was designed to evaluate the effects of tissue-type plasminogen activator (tPA) and 21- amino steroid (U74006F) in experimental embolic stroke in rabbits. The size of infarction from embolism was compared to controls with tPA alone, 21-amino steroid alone, and in combination. The middle cerebral artery of the rabbit was embolized by injecting an arterial ('white') thrombus in the right internal carotid artery. The rabbit treatment was 2 mg kg-1 of tissue-type plasminogen activator and/or 3 mg kg-1 of 21 amino steroid started at 2 h post-embolization. The animals were terminated 4 h post-treatment and brains were examined for evidence of ischemia and/or hemorrhage. Administration of tissue-type plasminogen activator and/or 21-amino steroid in the raw data show that there is a tendency for all treatments to reduce the ischemic volume when compared to the control group, also it is evident the standard deviation of these estimates is rather large when compared to the differences between treatments. The results of the analysis of variance shows that the differences expressed are not statistically significant. (No statistical differences were found between the treatment groups and the control group.) The results show that administration of tissue-type plasminogen activator and/or 21 amino steroid at 2 h post-embolization alone or in simultaneous administration does not significantly reduce the volume of infarction. Further studies need to be addressed in regards to the region of viable brain in the peri-infarct area, in reducing the time to treatment.

Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy

“…This database comprises data from 525 unique data sources, comprising 514 unique publications (15 contributed data to more than one review) and 11 unpublished communications, describing 1,359 experiments involving 19,956 animals (Table 1). Of these, only ten publications (2%; one publication [22] was represented in reviews of both tirilazad and tPA) described no significant effect on infarct volume, although four reported other statistically significant findings [23]–[26].…”

The Stroke Pharmacopeia: Promising Experimental Therapies

“…39 The compound limited cortical infarction and hastened metabolic recovery after transient focal ischemia in rats40 and reduced ischemic volume and improved cerebral blood flow in rabbits subjected to experimental embolic stroke. 41 Clinical trials with tirilazad of three escalating doses of tirilazad (0.6 mg/kg/day, 2.0 mg/kg/day, a n d 6.0 mg/kg/day) have been reported.42 Treatment was begun within 12 hours of stroke onset, and the median time from onset to treatment was 8.5 hours. Although tirilazad was well tolerated, 3-month outcomes in patients receiving placebo were better than in those receiving tirilazad, as measured by scores on the Glasgow Outcome Scale, National Institutes of Health (NIH) Stroke Scale, and Barthel Index.…”