Neuroprotective effects of volume-regulated anion channel blocker DCPIB on neonatal hypoxic-ischemic injury.

Aim: To evaluate the role of swelling-induced activation of volume-regulated anion channels (VRACs) in a neonatal hypoxic-ischemic injury model using the selective VRAC blocker 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on5-yl) oxobutyric acid (DCPIB).

Methods: Cerebral hypoxic-ischemic injury was induced in 7-day-old mouse pups with Rice-Vannucci method. Prior to the onset of ischemia, the animals were ip administered DCPIB (10 mg/kg).

Current understanding of TRPM7 pharmacology and drug development for stroke.

The initial excitement and countless efforts to find a pharmacological agent that disrupts the excitotoxic pathway of ischemic neuronal death have only led to disappointing clinical trials. Currently, a thrombolytic agent called recombinant tissue plasminogen activator (rt-PA) is the only pharmacological treatment available for patients with acute ischemic stroke in most countries. Even though its efficacy has been confirmed repeatedly, rt-PA is considerably underused due to reasons including a short therapeutic window and repeated complications associated with its use.

TRPM7 in cerebral ischemia and potential target for drug development in stroke.

Searching for effective pharmacological agents for stroke treatment has largely been unsuccessful. Despite initial excitement, antagonists for glutamate receptors, the most studied receptor channels in ischemic stroke, have shown insufficient neuroprotective effects in clinical trials. Outside the traditional glutamate-mediated excitotoxicity, recent evidence suggests few non-glutamate mechanisms, which may also cause ionic imbalance and cell death in cerebral ischemia.