The effect of biodegradable gelatin microspheres on the neuroprotective effects of high mobility group box 1 A box in the postischemic brain

Abstract

High mobility group box 1 (HMGB1) is a family of endogenous molecules that is released by necrotic cells and causes neuronal damages by triggering inflammatory processes In the cerebral ischemic brain sustained and regulated suppression of HMGB1 has been emerged as a therapeutic means to grant neuroprotection HMGB1 consists of two HMG boxes (A and B) and an acidic C-terminal tail and the A box peptide antagonistically competes with HMGB1 for its receptors In the middle cerebral artery occlusion (MCAO) in rats a murine model of transient cerebral ischemia administration of HMGB1 A box intraparenchymally after encapsulated in biodegradable gelatin microspheres (GMS) which enhances the stability of peptide inside and allows its sustained delivery at 1 h 3 h or 6 h after MCAO reduced mean infarct volumes by respectively 81 3% 42 6% and 30 7% of the untreated MCAO-brain along with remarkable improvement of neurological deficits Furthermore the administration of HMGB1 A box/GMS suppressed proinflammatory cytokine inductions more strongly than the injection of non-encapsulated HMGB1 A box Given that insulted brains-like ischemia have enhanced gelatinase activity than the normal brain our results suggest that GMS-mediated delivery of therapeutic peptides is a promising means to provide efficient neuroprotection in the postischemic brain.