GM130-silencing may aggravate blood-brain barrier damage and affect microglia polarization by down-regulating PD-L1 expression after experimental intracerebral hemorrhage

Mol Biol Rep. 2024 Aug 19;51(1):919. doi: 10.1007/s11033-024-09859-x.

Abstract

Background: In addition to primary injury, secondary injuries related to BBB disruption and immune-inflammatory response also play an important role in intracerebral hemorrhage (ICH). And the Golgi apparatus play an important role in the state of ICH.

Methods: ICH model and GM130-silencing ICH model were established in SD rats. The Garcia score was used to score the neurological defects of the rats. Blood-brain barrier (BBB) integrity were assessed by amount of extravasated Evans blue, and tight junction proteins. The expression of PD-L1 and GM130were detected through Western-blot and the subtype of microglia was showing with Immunofluorescence staining.

Results: Compared with the ICH group, GM130-silencing ICH rats got a worsened neurological deficit and enlarged volume of the hematoma. Evan's blue extravasation aggravated as well. The expression of GM130 in peri-hematoma tissue was further decreased, and the morphology and structure of the Golgi apparatus were further damaged. Meanwhile, the GM130 deficit resulted in decreased expression of PD-L1 and more polarization of microglia to the M1 subtype.

Conclusion: We demonstrate that GM130 could influence the integrity of BBB and plays a role in neuroinflammation via regulation of PD-L1 after ICH. The manipulation of GM130 might be a promising therapeutical target in ICH.

Keywords: GM130; Intracerebral hemorrhage; Microglia polarization; PD-L1.

MeSH terms

  • Animals
  • Autoantigens
  • B7-H1 Antigen* / genetics
  • B7-H1 Antigen* / metabolism
  • Blood-Brain Barrier* / metabolism
  • Blood-Brain Barrier* / pathology
  • Cerebral Hemorrhage* / genetics
  • Cerebral Hemorrhage* / metabolism
  • Cerebral Hemorrhage* / pathology
  • Disease Models, Animal
  • Down-Regulation
  • Golgi Apparatus / metabolism
  • Male
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Microglia* / metabolism
  • Microglia* / pathology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Autoantigens
  • B7-H1 Antigen
  • Golgin subfamily A member 2
  • Membrane Proteins