Related Experiment Video
Updated: Jul 20, 2026

Improved Method for the Preparation of a Human Cell-based, Contact Model of the Blood-Brain Barrier
Published on: November 12, 2013
Neutralizing the neurotoxic effects of exogenous and endogenous tPA
William M Armstead1, Taher Nassar, Saed Akkawi
1Department of Anesthesiology, University of Pennsylvania, 3620 Hamilton Walk, JM3, Philadelphia, Pennsylvania 19104, USA.
Abstract:
The clinical use of tissue-type plasminogen activator (tPA) in the treatment of stroke is profoundly constrained by its serious side effects. We report that the deleterious effects of tPA on cerebral edema and intracranial bleeding are separable from its fibrinolytic activity and can be neutralized. A hexapeptide (EEIIMD) corresponding to amino acids 350-355 of plasminogen activator inhibitor type 1 (PAI-1) abolished the tPA-induced increase in infarct size and intracranial bleeding in both mechanical and embolic models of stroke in rats, and reduced brain edema and neuronal loss after traumatic brain injury in pigs. These experiments suggest mechanisms to reduce the neurotoxic effects of tPA without compromising its fibrinolytic activity, through the use of selective antagonists and new tPA formulations.
Related Concept Videos
Pharmaceutical Poisoning: Treatment Strategies
Botulism
Tetanus
Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
The binding of dantrolene to the RYR1...
Drugs Affecting Neurotransmitter Synthesis
Anticholinesterase Agents: Poisoning and Treatment
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is slower than the...

