Bryostatin extends tPA time window to 6 h following middle cerebral artery occlusion in aged female rats.

Bryostatin extends tPA time window to 6 h following middle cerebral artery occlusion in aged female rats. Eur J Pharmacol. 2015 Jul 16; Authors: Tan Z, Lucke-Wold BP, Logsdon AF, Turner RC, Tan C, Li X, Hongpaison J, Alkon DL, Simpkins JW, Rosen CL, Huber JD Abstract Blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT) following ischemic /reperfusion injury contributes to post-stroke morbidity and mortality. Bryostatin, a potent protein kinase C (PKC) modulator, has shown promise in treating neurological injury. In the present study, we tested the hypothesis that administration of bryostatin would reduce BBB disruption and HT following acute ischemic stroke; thus, prolonging the time window for administering recombinant tissue plasminogen activator (r-tPA). Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18-20-month-old female rats using an autologous blood clot with delayed r-tPA reperfusion. Bryostatin (or vehicle) was administered at 2h post-MCAO and r-tPA was administered at 6h post-MCAO. Functional assessment, lesion volume, and hemispheric swelling measurements were performed at 24h post-MCAO. Assessment of BBB permeability, measurement of hemoglobin, assessment of matrix metalloproteinase (MMP) levels by gel zymography, and measurement of PKCε, PKCα, PKCδ expression by western blot were conducted at 24h post-MCAO. Rats treated with bryostatin pri...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research