PMID- 26640431
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151207
LR  - 20220310
IS  - 1662-5137 (Print)
IS  - 1662-5137 (Electronic)
IS  - 1662-5137 (Linking)
VI  - 9
DP  - 2015
TI  - Effects of Rapamycin Treatment on Neurogenesis and Synaptic Reorganization in the 
      Dentate Gyrus after Controlled Cortical Impact Injury in Mice.
PG  - 163
LID - 10.3389/fnsys.2015.00163 [doi]
LID - 163
AB  - Post-traumatic epilepsy (PTE) is one consequence of traumatic brain injury (TBI). 
      A prominent cell signaling pathway activated in animal models of both TBI and 
      epilepsy is the mammalian target of rapamycin (mTOR). Inhibition of mTOR with 
      rapamycin has shown promise as a potential modulator of epileptogenesis in 
      several animal models of epilepsy, but cellular mechanisms linking mTOR 
      expression and epileptogenesis are unclear. In this study, the role of mTOR in 
      modifying functional hippocampal circuit reorganization after focal TBI induced 
      by controlled cortical impact (CCI) was investigated. Rapamycin (3 or 10 mg/kg), 
      an inhibitor of mTOR signaling, was administered by intraperitoneal injection 
      beginning on the day of injury and continued daily until tissue collection. 
      Relative to controls, rapamycin treatment reduced dentate granule cell area in 
      the hemisphere ipsilateral to the injury two weeks post-injury. Brain injury 
      resulted in a significant increase in doublecortin immunolabeling in the dentate 
      gyrus ipsilateral to the injury, indicating increased neurogenesis shortly after 
      TBI. Rapamycin treatment prevented the increase in doublecortin labeling, with no 
      overall effect on Fluoro-Jade B staining in the ipsilateral hemisphere, 
      suggesting that rapamycin treatment reduced posttraumatic neurogenesis but did 
      not prevent cell loss after injury. At later times post-injury (8-13 weeks), 
      evidence of mossy fiber sprouting and increased recurrent excitation of dentate 
      granule cells was detected, which were attenuated by rapamycin treatment. 
      Rapamycin treatment also diminished seizure prevalence relative to 
      vehicle-treated controls after TBI. Collectively, these results support a role 
      for adult neurogenesis in PTE development and suggest that suppression of 
      epileptogenesis by mTOR inhibition includes effects on post-injury neurogenesis.
FAU - Butler, Corwin R
AU  - Butler CR
AD  - Department of Physiology, College of Medicine, University of Kentucky Lexington, 
      KY, USA.
FAU - Boychuk, Jeffery A
AU  - Boychuk JA
AD  - Department of Physiology, College of Medicine, University of Kentucky Lexington, 
      KY, USA ; Epilepsy Center, University of Kentucky Lexington, KY, USA ; Center for 
      Advanced Translational Stroke Science, University of Kentucky Lexington, KY, USA.
FAU - Smith, Bret N
AU  - Smith BN
AD  - Department of Physiology, College of Medicine, University of Kentucky Lexington, 
      KY, USA ; Epilepsy Center, University of Kentucky Lexington, KY, USA ; Spinal 
      Cord and Brain Injury Research Center (SCoBIRC), University of Kentucky 
      Lexington, KY, USA.
LA  - eng
GR  - R21 NS088608/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20151127
PL  - Switzerland
TA  - Front Syst Neurosci
JT  - Frontiers in systems neuroscience
JID - 101477946
PMC - PMC4661228
OTO - NOTNLM
OT  - adult neurogenesis
OT  - dentate granule cell
OT  - doublecortin
OT  - epilepsy
OT  - hippocampus
OT  - mTOR
OT  - mossy fiber sprouting
OT  - trauma
EDAT- 2015/12/08 06:00
MHDA- 2015/12/08 06:01
PMCR- 2015/01/01
CRDT- 2015/12/08 06:00
PHST- 2015/09/04 00:00 [received]
PHST- 2015/11/10 00:00 [accepted]
PHST- 2015/12/08 06:00 [entrez]
PHST- 2015/12/08 06:00 [pubmed]
PHST- 2015/12/08 06:01 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 10.3389/fnsys.2015.00163 [doi]
PST - epublish
SO  - Front Syst Neurosci. 2015 Nov 27;9:163. doi: 10.3389/fnsys.2015.00163. 
      eCollection 2015.