PMID- 30042663
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5153 (Print)
IS  - 1662-5153 (Electronic)
IS  - 1662-5153 (Linking)
VI  - 12
DP  - 2018
TI  - Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive 
      Impairments in D-Galactose-Induced Aged Mice.
PG  - 138
LID - 10.3389/fnbeh.2018.00138 [doi]
LID - 138
AB  - Neuroinflammation plays a critical role in the pathogenesis of postoperative 
      cognitive dysfunction (POCD) of the elderly patients. Receptor-interacting 
      protein kinase1 (RIPK1) is a key molecular switch modulating inflammation, 
      apoptosis and necroptosis. Here, we investigated whether inhibiting RIPK1 by 
      necrostatin-1 (Nec-1) could limit neuroinflammation and attenuate POCD in 
      D-Galactose (D-Gal)-induced aged mice. The mice were subjected to anesthesia and 
      partial hepatectomy, and necrostatin-1 was administered intraperitoneally 1 h 
      prior to anesthesia and surgery. Cognitive function and movement were tested 24 h 
      after surgery by open field, Barnes maze and puzzle box. The hippocampal tissues 
      were collected to detect the following: neuroinflammation (Iba-1, IL-1alpha, IL-1beta, 
      TNF-alpha), Necroptosis (Propidium Iodide (PI) labeling, RIPK1, nuclear transcription 
      factor kappa B (NF-kappaB) and neuroplasticity (doublecortin (DCX), NR2B, GluA1, 
      GluA2). We found that anesthesia and surgery induced a significant deficit in 
      spatial memory acquisition and impairment of executive function and memory to 
      simple task in D-Galactose-induced aged mice. Inhibiting RIPK1 by necrostatin-1 
      strikingly mitigated cognitive impairment and alleviated postoperative amplified 
      neuroinflammation, necroptosis and GluA1 loss in hippocampus. These suggest that 
      targeting RIPK1 by necrostatin-1 may serve as a promising therapeutics for 
      prevention of POCD in elderly patients.
FAU - Duan, Shangchun
AU  - Duan S
AD  - Department of Anesthesiology, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
FAU - Wang, Xueqin
AU  - Wang X
AD  - Center for Experimental Medicine, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
FAU - Chen, Gong
AU  - Chen G
AD  - Department of Anesthesiology, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
FAU - Quan, Chengxuan
AU  - Quan C
AD  - Department of Anesthesiology, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
FAU - Qu, Shuangquan
AU  - Qu S
AD  - Department of Anesthesiology, Hunan Children's Hospital, Changsha, China.
FAU - Tong, Jianbin
AU  - Tong J
AD  - Department of Anesthesiology, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
AD  - Center for Experimental Medicine, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
LA  - eng
PT  - Journal Article
DEP - 20180710
PL  - Switzerland
TA  - Front Behav Neurosci
JT  - Frontiers in behavioral neuroscience
JID - 101477952
PMC - PMC6048190
OTO - NOTNLM
OT  - cognitive deficit
OT  - elderly
OT  - necrostatin-1
OT  - neuroinflammation
OT  - surgery
EDAT- 2018/07/26 06:00
MHDA- 2018/07/26 06:01
PMCR- 2018/01/01
CRDT- 2018/07/26 06:00
PHST- 2018/03/26 00:00 [received]
PHST- 2018/06/18 00:00 [accepted]
PHST- 2018/07/26 06:00 [entrez]
PHST- 2018/07/26 06:00 [pubmed]
PHST- 2018/07/26 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnbeh.2018.00138 [doi]
PST - epublish
SO  - Front Behav Neurosci. 2018 Jul 10;12:138. doi: 10.3389/fnbeh.2018.00138. 
      eCollection 2018.