PMID- 25465043
OWN - NLM
STAT- MEDLINE
DCOM- 20150420
LR  - 20181113
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 35
IP  - 3
DP  - 2015 Mar
TI  - L-carnitine enhances axonal plasticity and improves white-matter lesions after 
      chronic hypoperfusion in rat brain.
PG  - 382-91
LID - 10.1038/jcbfm.2014.210 [doi]
AB  - Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative 
      stress and cognitive impairment. However, the biologic mechanisms that regulate 
      axonal plasticity under chronic cerebral hypoperfusion have not been fully 
      investigated. Here, we investigated whether L-carnitine, an antioxidant agent, 
      enhances axonal plasticity and oligodendrocyte expression, and explored the 
      signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion 
      model. Adult male Wistar rats subjected to ligation of the bilateral common 
      carotid arteries (LBCCA) were treated with or without L-carnitine. 
      L-carnitine-treated rats exhibited significantly reduced escape latency in the 
      Morris water maze task at 28 days after chronic hypoperfusion. Western blot 
      analysis indicated that L-carnitine increased levels of phosphorylated 
      high-molecular weight neurofilament (pNFH), concurrent with a reduction in 
      phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and 
      increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days 
      after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative 
      DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath 
      thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR 
      signaling pathway, and enhances axonal plasticity while concurrently ameliorating 
      oxidative stress and increasing oligodendrocyte myelination of axons, thereby 
      improving WMLs and cognitive impairment in a rat chronic hypoperfusion model.
FAU - Ueno, Yuji
AU  - Ueno Y
AD  - 1] Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan 
      [2] Department of Neurology, Juntendo University School of Medicine, Tokyo, 
      Japan.
FAU - Koike, Masato
AU  - Koike M
AD  - Department of Cell Biology and Neuroscience, Juntendo University School of 
      Medicine, Tokyo, Japan.
FAU - Shimada, Yoshiaki
AU  - Shimada Y
AD  - Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
FAU - Shimura, Hideki
AU  - Shimura H
AD  - Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan.
FAU - Hira, Kenichiro
AU  - Hira K
AD  - Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
FAU - Tanaka, Ryota
AU  - Tanaka R
AD  - Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
FAU - Uchiyama, Yasuo
AU  - Uchiyama Y
AD  - 1] Department of Cell Biology and Neuroscience, Juntendo University School of 
      Medicine, Tokyo, Japan [2] Department of Cellular and Molecular Neuropathology, 
      Juntendo University Graduate School of Medicine, Tokyo, Japan.
FAU - Hattori, Nobutaka
AU  - Hattori N
AD  - Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
FAU - Urabe, Takao
AU  - Urabe T
AD  - Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141203
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Neuroprotective Agents)
RN  - 12001-76-2 (Vitamin B Complex)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - Animals
MH  - Axons/drug effects
MH  - Blotting, Western
MH  - Brain Ischemia/*pathology
MH  - Carnitine/*pharmacology
MH  - Disease Models, Animal
MH  - Immunohistochemistry
MH  - Male
MH  - Maze Learning/drug effects
MH  - Neuronal Plasticity/*drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Oxidative Stress/physiology
MH  - Rats
MH  - Vitamin B Complex/pharmacology
MH  - White Matter/drug effects/*pathology
PMC - PMC4348379
EDAT- 2014/12/04 06:00
MHDA- 2015/04/22 06:00
PMCR- 2016/03/01
CRDT- 2014/12/04 06:00
PHST- 2014/08/30 00:00 [received]
PHST- 2014/10/28 00:00 [revised]
PHST- 2014/10/30 00:00 [accepted]
PHST- 2014/12/04 06:00 [entrez]
PHST- 2014/12/04 06:00 [pubmed]
PHST- 2015/04/22 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - jcbfm2014210 [pii]
AID - 10.1038/jcbfm.2014.210 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2015 Mar;35(3):382-91. doi: 10.1038/jcbfm.2014.210. 
      Epub 2014 Dec 3.