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

Title
The effect of biodegradable gelatin microspheres on the neuroprotective effects of high mobility group box 1 A box in the postischemic brain
Authors
Jin Y.-C.Kim S.-W.Cheng F.Shin J.-H.Park J.-K.Lee S.Lee J.-E.Han P.-L.Lee M.Kim K.K.Choi H.Lee J.-K.
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2011
Journal Title
Biomaterials
ISSN
0142-9612JCR Link
Citation
vol. 32, no. 3, pp. 899 - 908
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2010 Elsevier Ltd.
DOI
10.1016/j.biomaterials.2010.09.054
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일반대학원 > 뇌·인지과학과 > Journal papers
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