PMID- 30178866
OWN - NLM
STAT- MEDLINE
DCOM- 20191105
LR  - 20191105
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 22
IP  - 16
DP  - 2018 Aug
TI  - Research on ketamine in mediating autophagy and inhibiting apoptosis of 
      astrocytes in cerebral cortex of rats through NF-kappaB pathway.
PG  - 5385-5393
LID - 15741 [pii]
LID - 10.26355/eurrev_201808_15741 [doi]
AB  - OBJECTIVE: To investigate the effects of ketamine on autophagy and apoptosis of 
      astrocytes in the cerebral cortex of rats, and determine whether nuclear 
      factor-kappaB (NF-kappaB) pathway is involved in the regulation of autophagy and 
      apoptosis of astrocytes. MATERIALS AND METHODS: A total of 36 male Sprague-Dawley 
      (SD) rats were randomly divided into 3 groups: control group (Group C: 
      intraperitoneal injection of equal amount of normal saline), glutamic acid group 
      (Group G: intraperitoneal injection of 1 mg/kg glutamic acid) and glutamic acid + 
      ketamine group (Group GK: intraperitoneal injection of 1 mg/kg glutamic acid and 
      then injection of 5 mg/kg ketamine after 30 min). The cerebral cortex of rats in 
      each group was taken after successive administration for 5 d. The number of glial 
      fibrillary acidic protein (GFAP)-positive cells in the cerebral cortex of rats in 
      each group was detected via immunofluorescence. The number of terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive 
      cells (apoptotic cells) in the cerebral cortex was detected via TUNEL staining. 
      The levels of inflammatory factors were detected using the enzyme-linked 
      immunosorbent assay (ELISA) kit. Moreover, the expressions of autophagy-related 
      proteins and apoptosis-related proteins in the cerebral cortex were detected via 
      Western blotting, and the expressions of IkappaB-a and NF-kappaBp65 were also detected. 
      RESULTS: The results of immunofluorescence showed that the number of 
      GFAP-positive cells in the cerebral cortex of rats in Group G was significantly 
      increased compared with that in Group C (p<0.01), and it was significantly 
      decreased in Group GK compared with that in Group G (p<0.01). The results of 
      TUNEL staining revealed that the number of TUNEL-positive cells in the cerebral 
      cortex in Group G was significantly larger than that in Group C, and it was 
      significantly smaller in Group GK than that in Group G (p<0.01). Results of ELISA 
      demonstrated that compared with those in Group C, the contents of interleukin-6 
      (IL-6) and tumor necrosis factor-a (TNF-a) in Group G were significantly 
      increased (p<0.01), but the content of IL-10 was significantly decreased 
      (p<0.01). Compared with those in Group G, the contents of IL-6 and TNF-a in Group 
      GK were significantly decreased (p<0.01), but the level of IL-10 was 
      statistically elevated (p<0.01). Compared with those in Group C, the levels of 
      LC3 II/I and cleaved caspase-3 in the cerebral cortex in Group G were 
      significantly increased (p<0.01), but the p62 level and B-cell lymphoma-2/Bcl-2 
      associated X protein (Bcl-2/Bax) ratio were significantly decreased (p<0.01). In 
      Group GK, the levels of LC3 II/I and cleaved caspase-3 were reduced, but the p62 
      level and Bcl-2/Bax ratio were increased. The expressions of IkappaB-alpha and NF-kappaBp65 
      in Group G were significantly decreased compared with those in Group C (p<0.01), 
      and they were significantly higher in Group GK than those in Group G (p<0.01). 
      CONCLUSIONS: Ketamine can reduce the glutamic acid-induced activation of 
      astrocytes in the cerebral cortex, inhibit the autophagy and alleviate the 
      apoptosis of astrocytes, the process of which is mediated by the NF-kappaB pathway, 
      which provides the new molecular basis of ketamine in protecting astrocytes.
FAU - Yang, J
AU  - Yang J
AD  - Department of Anesthesiology, First People's Hospital of Changzhou & Third 
      Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China. 
      TaoHonghj@163.com.
FAU - Li, X
AU  - Li X
FAU - Yang, C
AU  - Yang C
FAU - Bu, X-X
AU  - Bu XX
FAU - Shen, J
AU  - Shen J
FAU - Hong, T
AU  - Hong T
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Astrocytes/*metabolism
MH  - Autophagy/*drug effects
MH  - Cerebral Cortex/*metabolism
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - I-kappa B Proteins/metabolism
MH  - Interleukin-6/metabolism
MH  - Ketamine/*pharmacology
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2018/09/05 06:00
MHDA- 2019/11/07 06:00
CRDT- 2018/09/05 06:00
PHST- 2018/09/05 06:00 [entrez]
PHST- 2018/09/05 06:00 [pubmed]
PHST- 2019/11/07 06:00 [medline]
AID - 15741 [pii]
AID - 10.26355/eurrev_201808_15741 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2018 Aug;22(16):5385-5393. doi: 
      10.26355/eurrev_201808_15741.