PMID- 30666179
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 12
DP  - 2018
TI  - Inhibition of Necroptosis Rescues SAH-Induced Synaptic Impairments in Hippocampus 
      via CREB-BDNF Pathway.
PG  - 990
LID - 10.3389/fnins.2018.00990 [doi]
LID - 990
AB  - Subarachnoid hemorrhage (SAH) is a devastating form of stroke that leads to 
      incurable outcomes. Increasing evidence has proved that early brain injury (EBI) 
      contributes mostly to unfavorable outcomes after SAH. A previously unknown 
      mechanism of regulated cell death known as necroptosis has recently been 
      reported. Necrostatin-1 (nec-1), a specific and potent inhibitor of necroptosis, 
      can attenuate brain impairments after SAH. However, the effect of nec-1 on the 
      hippocampus and its neuroprotective impact on synapses after SAH is not well 
      understood. Our present study was designed to investigate the potential effects 
      of nec-1 administration on synapses and its relevant signal pathway in EBI after 
      SAH. Nec-1 was administrated in a rat model via intracerebroventricular injection 
      after SAH. Neurobehavior scores and brain edema were detected at 24 h after SAH 
      occurred. The expression of the receptor-interacting proteins 1 and 3 (RIP1and3) 
      was examined as a marker of necroptosis. We used hematoxylin and eosin staining, 
      Nissl staining, silver staining and terminal deoxynucleotidyl transferase dUTP 
      nick end labeling (TUNEL) to observe the morphological changes in hippocampus. 
      The protective effect of nec-1 on synapses was evaluated using western blotting 
      and electron microscopy and Western blotting was used to detect the cAMP 
      responsive element binding (CREB) protein and brain-derived neurotrophic factor 
      (BDNF), and we used transmission electron microscopy and TUNEL to detect the 
      protective effects of nec-1 when a specific inhibitor of CREB, known as 666-15, 
      was used. Our results showed that in the SAH group, RIP1, and RIP3 significantly 
      increased in the hippocampus. Additionally, injection of nec-1 alleviated brain 
      edema and improved neurobehavior scores, compared with those in the SAH group. 
      The damage to neurons was attenuated, and synaptic structure also improved in the 
      Sham+nec-1 group. Furthermore, nec-1 treatment significantly enhanced the levels 
      of phospho-CREB and BDNF compared with those in the SAH group. The protective 
      effect of nec-1 could hindered by 666-15. Thus, nec-1 mitigated SAH-induced 
      synaptic impairments in the hippocampus through the inhibition of necroptosis in 
      connection with the CREB-BDNF pathway. This study may provide a new strategy for 
      SAH patients in clinical practice.
FAU - Yang, Chunlei
AU  - Yang C
AD  - Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of 
      Brain and Brain-Inspired Science, Shandong University, Jinan, China.
AD  - Shandong Key Laboratory of Brain Function Remodeling, Jinan, China.
FAU - Li, Tong
AU  - Li T
AD  - Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of 
      Brain and Brain-Inspired Science, Shandong University, Jinan, China.
AD  - Shandong Key Laboratory of Brain Function Remodeling, Jinan, China.
AD  - Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao, China.
FAU - Xue, Hao
AU  - Xue H
AD  - Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of 
      Brain and Brain-Inspired Science, Shandong University, Jinan, China.
AD  - Shandong Key Laboratory of Brain Function Remodeling, Jinan, China.
FAU - Wang, Lingxiao
AU  - Wang L
AD  - Department of Physiology, Shandong University School of Basic Medical Sciences, 
      Jinan, China.
FAU - Deng, Lin
AU  - Deng L
AD  - Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of 
      Brain and Brain-Inspired Science, Shandong University, Jinan, China.
AD  - Shandong Key Laboratory of Brain Function Remodeling, Jinan, China.
FAU - Xie, Yunkai
AU  - Xie Y
AD  - Department of Physiology, Shandong University School of Basic Medical Sciences, 
      Jinan, China.
FAU - Bai, Xuemei
AU  - Bai X
AD  - Department of Physiology, Shandong University School of Basic Medical Sciences, 
      Jinan, China.
FAU - Xin, Danqing
AU  - Xin D
AD  - Department of Physiology, Shandong University School of Basic Medical Sciences, 
      Jinan, China.
FAU - Yuan, Hongtao
AU  - Yuan H
AD  - Department of Physiology, Shandong University School of Basic Medical Sciences, 
      Jinan, China.
FAU - Qiu, Jie
AU  - Qiu J
AD  - Department of Physiology, Shandong University School of Basic Medical Sciences, 
      Jinan, China.
FAU - Wang, Zhen
AU  - Wang Z
AD  - Department of Physiology, Shandong University School of Basic Medical Sciences, 
      Jinan, China.
FAU - Li, Gang
AU  - Li G
AD  - Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of 
      Brain and Brain-Inspired Science, Shandong University, Jinan, China.
AD  - Shandong Key Laboratory of Brain Function Remodeling, Jinan, China.
LA  - eng
PT  - Journal Article
DEP - 20190107
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC6330293
OTO - NOTNLM
OT  - early brain injury
OT  - hippocampus
OT  - necroptosis
OT  - subarachnoid hemorrhage
OT  - synaptic impairment
EDAT- 2019/01/23 06:00
MHDA- 2019/01/23 06:01
PMCR- 2018/01/01
CRDT- 2019/01/23 06:00
PHST- 2018/05/23 00:00 [received]
PHST- 2018/12/10 00:00 [accepted]
PHST- 2019/01/23 06:00 [entrez]
PHST- 2019/01/23 06:00 [pubmed]
PHST- 2019/01/23 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2018.00990 [doi]
PST - epublish
SO  - Front Neurosci. 2019 Jan 7;12:990. doi: 10.3389/fnins.2018.00990. eCollection 
      2018.