PMID- 32687486
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20211204
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 26
DP  - 2020 Jul 20
TI  - Pyrazolo[4,3-c]pyridine-4-one (PP-4-one) Exhibits Anti-Epileptogenic Effect in 
      Rat Model of Traumatic Epilepsy by Mammalian Target of Rapamycin (mTOR) Signaling 
      Pathway Downregulation.
PG  - e923919
LID - 10.12659/MSM.923919 [doi]
AB  - BACKGROUND Post-traumatic epilepsy (PTE) is a common type of acquired epilepsies 
      secondary to traumatic brain injury (TBI), accounting for approximately 10-25% of 
      patients. The present study evaluated activity of PP-4-one against mTOR signaling 
      activation in a rat model of FeCl(2)-induced post-traumatic epilepsy. MATERIAL AND 
      METHODS Epilepsy in rats was induced by injecting 10 microl FeCl(2) (concentration 100 
      mM) at a uniform rate of 1 microl/minute. The iNOS expression was detected using a 
      Leica microscope connected to a digital camera system. Reverse transcription 
      polymerase chain reaction (RT‑PCR) was used for determination of NR1 mRNA 
      expression. RESULTS The post-traumatic epilepsy induced neuronal degeneration in 
      the hippocampus and frontal cortex of the rats. Treatment with PP-4-one prevented 
      neuronal degeneration in the hippocampus and frontal cortex in rats with 
      post-traumatic epilepsy. The data revealed markedly higher levels of p-mTOR and 
      p-P70S6K in rat hippocampal tissues after induction of traumatic epilepsy. 
      Treatment of post-traumatic epilepsy rats with PP-4-one significantly suppressed 
      p-mTOR and p-P70S6K expression, and PP-4-one treatment reduced epileptic brain 
      injury in the rats with post-traumatic epilepsy. CONCLUSIONS PP-4-one exhibits an 
      anti-epileptogenic effect in the rat model of PTE by inhibiting behavioral 
      seizures through suppression of iNOS and astrocytic proliferation. Moreover, 
      PP-4-one treatment suppressed NR1 expression and targeted the mTOR pathway in 
      PTE-induced rats. Thus, PP-4-one shows promise as a novel and effective 
      therapeutic agent for treatment of epilepsy induced by PTE.
FAU - Jin, Jungong
AU  - Jin J
AD  - Department of Neurosurgery, Xi'an International Medical Center Hospital, Xi'an, 
      Shaanxi, China (mainland).
FAU - Shen, Xi
AU  - Shen X
AD  - Clinical Experimental Center, Xi'an International Medical Center Hospital, Xi'an, 
      Shaanxi, China (mainland).
FAU - Tian, Lu
AU  - Tian L
AD  - Department of Neurology, Xi'an International Medical Center Hospital, Xi'an, 
      Shaanxi, China (mainland).
FAU - He, Guoyishi
AU  - He G
AD  - Department of Neurosurgery, Xi'an International Medical Center Hospital, Xi'an, 
      Shaanxi, China (mainland).
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Department of Neurology, Xi'an International Medical Center Hospital, Xi'an, 
      Shaanxi, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20200720
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Anticonvulsants)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 0 (pyrazolo(3,4-b)pyridine)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/pharmacology
MH  - Astrocytes/metabolism
MH  - Brain/metabolism
MH  - Brain Injuries
MH  - Brain Injuries, Traumatic
MH  - Disease Models, Animal
MH  - Epilepsy/drug therapy/metabolism
MH  - Epilepsy, Post-Traumatic/*drug therapy/metabolism
MH  - Frontal Lobe/metabolism
MH  - Hippocampus/metabolism
MH  - Male
MH  - Pyrazoles/*chemistry/*pharmacology
MH  - Pyridines/*chemistry/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases, 70-kDa/drug effects/metabolism
MH  - Seizures
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/drug effects/metabolism
PMC - PMC7392056
EDAT- 2020/07/21 06:00
MHDA- 2021/04/28 06:00
PMCR- 2020/07/20
CRDT- 2020/07/21 06:00
PHST- 2020/07/21 06:00 [entrez]
PHST- 2020/07/21 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2020/07/20 00:00 [pmc-release]
AID - 923919 [pii]
AID - 10.12659/MSM.923919 [doi]
PST - epublish
SO  - Med Sci Monit. 2020 Jul 20;26:e923919. doi: 10.12659/MSM.923919.