title: Neuroserpin Protects Rat Neurons and Microglia-Mediated Inflammatory Response Against Oxygen-Glucose Deprivation- and Reoxygenation Treatments in an In Vitro Study.
abstract: OBJECTIVE
  Neuroserpin (NSP) is known for its neuroprotective role in cerebral ischemic animal models and patients. Our laboratory conducted a series of investigations on the neuroprotection of NSP in different cells in the brain. In the present study, we further observe the effects of NSP on neurons and microglia-mediated inflammatory response following oxygen-glucose deprivation (OGD), and explore possible mechanisms related to neuroprotection of OGD in the central nervous system (CNS).
  
  
  METHODS
  Neurons and microglia from neonatal rats were treated with OGD followed by reoxygenation (OGD/R). To confirm the effects of NSP, the neuronal survival, neuronal apoptosis, and lactate dehydrogenase (LDH) release were measured in cultured neurons. Furthermore, the levels of IL-1β and nitric oxide (NO) release were also detected in cultured microglia. The possible mechanisms for the neuroprotective effect of NSP were explored using Western blot analysis.
  
  
  RESULTS
  NSP administration can reverse abnormal variations in neurons and microglia-mediated inflammatory response induced by OGD/R processes. The neuronal survival rate, neuronal apoptosis rate, and LDH release were significantly improved by NSP administration in neurons. Simultaneously, the release of IL-1β and NO were significantly reduced by NSP in microglia. Western blot showed that the expression of ERK, P38, and JNK was upregulated in microglia by the OGD/R treatment, and these effects were significantly inhibited by NSP.
  
  
  CONCLUSIONS
  These data verified the neuroprotective effects of NSP on neurons and microglia-mediated inflammatory response. Inhibition of the mitogen-activated protein kinase (MAPK) signaling pathways might play a potential role in NSP neuroprotection on microglia-mediated inflammatory response, which needs further verification.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Yang
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Asakawa
authors.forename: Sha
authors.initials: S
authors.lastname: Han
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Weiwen
authors.initials: W
authors.lastname: Wu
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Luo
authors.forename: Wenjie
authors.initials: W
authors.lastname: Cao
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Baoguo
authors.initials: B
authors.lastname: Xiao
authors.forename: Hiroki
authors.initials: H
authors.lastname: Namba
authors.forename: Chuanzhen
authors.initials: C
authors.lastname: Lu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097522:Neuroserpin
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose; D053583:Interleukin-1beta; D048031:JNK Mitogen-Activated Protein Kinases; D007770:L-Lactate Dehydrogenase; D009479:Neuropeptides; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D010100:Oxygen; D015843:Serpins; D048051:p38 Mitogen-Activated Protein Kinases; D000097522:Neuroserpin