Preclinical evaluation of postischemic dehydroascorbic Acid administration in a large-animal stroke model

Area of Science:

• Neuroscience
• Translational Medicine
• Pharmacology

Background:

• Dehydroascorbic acid (DHA), a form of ascorbic acid, shows neuroprotective effects in rodent stroke models.
• DHA can cross the blood-brain barrier, making it a potential therapeutic agent for stroke.

Purpose of the Study:

• To evaluate the efficacy of postischemic DHA administration in a large-animal stroke model.
• To determine if DHA can be translated into a human clinical trial for stroke treatment.

Main Methods:

• Thirty-six adult male baboons underwent transient cerebral artery occlusion via transorbital craniectomy.
• Animals received either 500 mg/kg of DHA or vehicle post-stroke.
• Infarct volume (MRI) and neurological function were primary outcome measures.

Main Results:

• Midpoint interim analysis (n=9 per group) showed no significant improvement in infarct volume or neurological function with DHA.
• The study was terminated due to statistical futility.
• Postischemic DHA administration did not confirm neuroprotective effects in this large-animal model.

Conclusions:

• The neuroprotective effect of DHA observed in rodents was not replicated in the baboon stroke model.
• Current dosing strategies for DHA may not be effective in larger animals or humans.
• Further investigation into DHA efficacy is required before considering clinical translation for stroke.