bimoclomol and Subarachnoid-Hemorrhage

Bimoclomol (BRLP-42) is a novel antiischemic compound acting against peripheral vascular complications of diabetes mellitus (neuropathy, retinopathy, and nephropathy). In the present study the activity of bimoclomol was tested in experimental subarachnoid hemorrhage (SAH) and arachidonic acid (AA)-induced brain edema in rats to elucidate whether the compound may also have beneficial effect in cerebrovascular disturbances. For comparison, a neuroprotective AMPA antagonist, GYKI-52466, was examined. Injury caused by autologous intracranial blood injection or sodium-arachidonate was evaluated by the damage of blood-brain barrier (BBB) reflected in the extravasation of Evans blue dye into the cerebral tissue. Bimoclomol (2 x 2 mg/kg IV) markedly reduced, while GYKI-52466 (2 x 2 mg/kg IV) moderately diminished the extravasation produced by SAH (39.9%, p < 0.01 and 26.7%, p > 0.05, respectively). In the case of AA-induced brain edema, bimoclomol showed less pronounced (19.6%, p < 0.05) inhibitory action, and GYKI-52466 seemed to be more effective (34.2%, p < 0.05). These results suggest that bimoclomol may be active not only in peripheral micro- and macroangiopathy, but also in some types of cerebrovascular disorders.

Topics: Animals; Anti-Anxiety Agents; Arachidonic Acid; Benzodiazepines; Brain Edema; Cerebral Angiography; Cerebrovascular Circulation; Excitatory Amino Acid Antagonists; Imides; Male; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Subarachnoid Hemorrhage