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

Yin Chuan Jin, Seung Woo Kim, Felice Cheng, Joo Hyun Shin, Jin Kuen Park, Sanghyun Lee, Jung Eun Lee, Pyung Lim Han, Minhyung Lee, Kyekyoon Kevin Kim, Hyungsoo Choi, Ja Kyeong Lee

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)899-908
Number of pages10
JournalBiomaterials
Volume32
Issue number3
DOIs
StatePublished - Jan 1 2011

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Keywords

  • A box
  • Brain ischemia
  • Gelatin microsphere
  • HMGB1
  • MCAO
  • Neuroprotection

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

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. (2011). The effect of biodegradable gelatin microspheres on the neuroprotective effects of high mobility group box 1 A box in the postischemic brain. Biomaterials, 32(3), 899-908. https://doi.org/10.1016/j.biomaterials.2010.09.054