PMID- 31020769
OWN - NLM
STAT- MEDLINE
DCOM- 20201019
LR  - 20210109
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 25
IP  - 10
DP  - 2019 Oct
TI  - Secukinumab attenuates reactive astrogliosis via IL-17RA/(C/EBPbeta)/SIRT1 pathway 
      in a rat model of germinal matrix hemorrhage.
PG  - 1151-1161
LID - 10.1111/cns.13144 [doi]
AB  - AIMS: Reactive astrogliosis plays a critical role in neurological deficits after 
      germinal matrix hemorrhage (GMH). It has been reported that interleukin-17A and 
      IL-17A receptor IL-17RA/(C/EBPbeta)/SIRT1 signaling pathway enhances reactive 
      astrogliosis after brain injuries. We evaluated the effects of secukinumab on 
      reactive astrogliosis in a rat pup model of GMH. METHODS: A total of 146 Sprague 
      Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of 
      collagenase. Secukinumab was administered intranasally 1 hour post-GMH. C/EBPbeta 
      CRISPR or SIRT1 antagonist EX527 was administrated intracerebroventricularly 
      (icv) 48 hours and 1 hour before GMH induction, respectively. Neurobehavior, 
      Western blot, histology, and immunohistochemistry were used to assess treatment 
      regiments in the short term and long term. RESULTS: The endogenous IL-17A, 
      IL-17RA, C/EBPbeta, and GFAP and proliferation marker CyclinD1 were increased, while 
      SIRT1 expression was decreased after GMH. Secukinumab treatment improved 
      neurological deficits, reduced ventriculomegaly, and increased cortical 
      thickness. Additionally, treatment increased SIRT1 expression and lowered 
      proliferation proteins PCNA and CyclinD1 as well as GFAP expression. C/EBPbeta 
      CRISPR activation plasmid and EX527 reversed the antireactive astrogliosis 
      effects of secukinumab. CONCLUSION: Secukinumab attenuated reactive astrogliosis 
      and reduced neurological deficits after GMH, partly by regulating 
      IL-17RA/(C/EBPbeta)/SIRT1 pathways. Secukinumab may provide a promising therapeutic 
      strategy for GMH patients.
CI  - (c) 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & 
      Sons Ltd.
FAU - Liu, Sheng-Peng
AU  - Liu SP
AD  - Department of Pediatrics, Affiliated Haikou Hospital of Xiangya Medical College, 
      Central South University, Haikou, China.
AD  - Department of Physiology and Pharmacology, School of Medicine, Loma Linda 
      University, Loma Linda, California.
FAU - Huang, Lei
AU  - Huang L
AD  - Department of Physiology and Pharmacology, School of Medicine, Loma Linda 
      University, Loma Linda, California.
AD  - Department of Neurosurgery, School of Medicine, Loma Linda University, Loma 
      Linda, California.
FAU - Flores, Jerry
AU  - Flores J
AD  - Department of Physiology and Pharmacology, School of Medicine, Loma Linda 
      University, Loma Linda, California.
FAU - Ding, Yan
AU  - Ding Y
AD  - Department of Physiology and Pharmacology, School of Medicine, Loma Linda 
      University, Loma Linda, California.
FAU - Li, Peng
AU  - Li P
AD  - Department of Physiology and Pharmacology, School of Medicine, Loma Linda 
      University, Loma Linda, California.
FAU - Peng, Jun
AU  - Peng J
AD  - Department of Physiology and Pharmacology, School of Medicine, Loma Linda 
      University, Loma Linda, California.
FAU - Zuo, Gang
AU  - Zuo G
AD  - Department of Physiology and Pharmacology, School of Medicine, Loma Linda 
      University, Loma Linda, California.
FAU - Zhang, John H
AU  - Zhang JH
AD  - Department of Physiology and Pharmacology, School of Medicine, Loma Linda 
      University, Loma Linda, California.
AD  - Department of Neurosurgery, School of Medicine, Loma Linda University, Loma 
      Linda, California.
AD  - Department of Anesthesiology, School of Medicine, Loma Linda University, Loma 
      Linda, California.
FAU - Lu, Jun
AU  - Lu J
AD  - Department of Pediatrics, Affiliated Haikou Hospital of Xiangya Medical College, 
      Central South University, Haikou, China.
FAU - Tang, Ji-Ping
AU  - Tang JP
AUID- ORCID: 0000-0002-2392-9280
AD  - Department of Physiology and Pharmacology, School of Medicine, Loma Linda 
      University, Loma Linda, California.
LA  - eng
GR  - R21 NS101284/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190424
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Il17ra protein, mouse)
RN  - 0 (Receptors, Interleukin-17)
RN  - DLG4EML025 (secukinumab)
RN  - EC 3.5.1.- (Sirt1 protein, rat)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Administration, Intranasal
MH  - Animals
MH  - Animals, Newborn
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage
MH  - Astrocytes/drug effects/metabolism
MH  - Cerebral Hemorrhage/drug therapy/*metabolism
MH  - *Disease Models, Animal
MH  - Female
MH  - Gliosis/drug therapy/*metabolism
MH  - Male
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Interleukin-17/*metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Sirtuin 1/*metabolism
PMC - PMC6776744
OTO - NOTNLM
OT  - IL-17A
OT  - neurobehavior
OT  - reactive astrogliosis
OT  - secukinumab
COIS- The authors declare no conflicts of interest.
EDAT- 2019/04/26 06:00
MHDA- 2020/10/21 06:00
PMCR- 2019/04/24
CRDT- 2019/04/26 06:00
PHST- 2019/02/13 00:00 [received]
PHST- 2019/04/08 00:00 [revised]
PHST- 2019/04/09 00:00 [accepted]
PHST- 2019/04/26 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/04/26 06:00 [entrez]
PHST- 2019/04/24 00:00 [pmc-release]
AID - CNS13144 [pii]
AID - 10.1111/cns.13144 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2019 Oct;25(10):1151-1161. doi: 10.1111/cns.13144. Epub 2019 
      Apr 24.