PMID- 31556575
OWN - NLM
STAT- MEDLINE
DCOM- 20200220
LR  - 20200220
IS  - 1509-572X (Electronic)
IS  - 1509-572X (Linking)
VI  - 57
IP  - 2
DP  - 2019
TI  - Inactivation of P2YR12 contributes to isoflurane-induced neuronal injury by 
      altering TLR-4/BDNF/TNF-alpha.
PG  - 161-169
LID - 37042 [pii]
LID - 10.5114/fn.2019.86295 [doi]
AB  - The present investigation evaluated the effect of inhibiting the P2Y12 gene on 
      anaesthetic-induced neuronal injury in a rat model. Neuronal injury was induced 
      by exposing the animals for 6 h to 30% oxygen containing 0.75% isoflurane and 1.2 
      mg/kg prasugrel (a P2Y12 inhibitor) p.o. for 14 days. Cognitive function was 
      determined by the Morris water maze, and the neurological severity score was 
      determined. Enzyme-linked immunosorbent assay was used to estimate the level of 
      oxidative stress and mediators of inflammation in brain tissues of 
      isoflurane-induced neuronal injury rats. Apoptosis of neuronal cells was 
      estimated by terminal deoxynucleotidyl transferase dUTP nick end labelling 
      (TUNEL) and western blot assays. Real time-polymerase chain reaction was 
      performed to estimate the expression levels of several proteins. The data 
      revealed that inhibiting the P2Y12 gene ameliorated changes in the modified 
      neurological severity score and cognitive function in neuronal injury rats. 
      Moreover the levels of proinflammatory mediators, oxidative stress, and cyclic 
      AMP, and the number of TUNEL-positive cells, decreased significantly (p < 0.01) 
      in the prasugrel-treated group compared to the negative control group. In 
      addition, apoptosis of neuronal cells decreased in the prasugrel-treated group, 
      as it ameliorated expression of the PI3K, Bcl-2, Bad, and Akt proteins in the 
      isoflurane-induced neuronal injury rats. Expression of brain-derived neurotrophic 
      factor (BDNF) and tropomyosin receptor kinase B (TrkB) proteins was enhanced, 
      whereas the Toll-like receptor-4 (TLR-4) and nuclear factor kappaB (NF-kappaB) proteins 
      decreased in the brain tissues of the prasugrel-treated group compared to the 
      negative control group of rats. These results suggest that inhibiting the P2YR12 
      gene protects against neuronal injury in isoflurane-induced neuronal injury rats. 
      Inhibiting the P2YR12 gene ameliorated neuronal apoptosis by regulating the 
      BDNF/TLR-4/TNF-alpha pathway.
FAU - Sun, Nenghong
AU  - Sun N
AD  - Department of Anesthesiology, Weifang People's Hospital, Weifang, Shandong, 
      China.
FAU - Chu, Lichao
AU  - Chu L
AD  - Department of Anesthesiology, Weifang People's Hospital, Weifang, Shandong, 
      China.
FAU - Yuan, Lei
AU  - Yuan L
AD  - Department of Operating Theatre, Weifang Seventh People's Hospital, Weifang, 
      Shandong, China.
FAU - Qi, Zongcai
AU  - Qi Z
AD  - Department of Anesthesiology, Weifang People's Hospital, Weifang, Shandong, 
      China.
LA  - eng
PT  - Journal Article
PL  - Poland
TA  - Folia Neuropathol
JT  - Folia neuropathologica
JID - 9437431
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Purinergic P2 Receptor Antagonists)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - CYS9AKD70P (Isoflurane)
RN  - E0399OZS9N (Cyclic AMP)
RN  - G89JQ59I13 (Prasugrel Hydrochloride)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cognition/drug effects
MH  - Cyclic AMP/metabolism
MH  - Isoflurane/*toxicity
MH  - Maze Learning/drug effects
MH  - Neurons/drug effects/*metabolism
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Prasugrel Hydrochloride/pharmacology
MH  - Purinergic P2 Receptor Antagonists/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Purinergic P2/metabolism
MH  - Toll-Like Receptor 4/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
OTO - NOTNLM
OT  - TUNEL assay
OT  - isoflurane
OT  - neuronal injury
OT  - prasugrel
OT  - P2Y12 gene
EDAT- 2019/09/27 06:00
MHDA- 2020/02/23 06:00
CRDT- 2019/09/27 06:00
PHST- 2019/09/27 06:00 [entrez]
PHST- 2019/09/27 06:00 [pubmed]
PHST- 2020/02/23 06:00 [medline]
AID - 37042 [pii]
AID - 10.5114/fn.2019.86295 [doi]
PST - ppublish
SO  - Folia Neuropathol. 2019;57(2):161-169. doi: 10.5114/fn.2019.86295.