PMID- 28487988
OWN - NLM
STAT- MEDLINE
DCOM- 20180305
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 15
IP  - 6
DP  - 2017 Jun
TI  - Delayed administration of guanosine improves long‑term functional recovery and 
      enhances neurogenesis and angiogenesis in a mouse model of photothrombotic 
      stroke.
PG  - 3999-4004
LID - 10.3892/mmr.2017.6521 [doi]
AB  - Guanosine (GUO) is neuroprotective when administered acutely for the treatment of 
      cerebral ischemia. The aim of the present study was to investigate whether 
      delayed administration of GUO improved long‑term functional recovery following 
      stroke, as well as to explore the potential underlying mechanisms. GUO (8 mg/kg) 
      or a vehicle was administered intraperitoneally for 7 consecutive days beginning 
      24 h prior to photothrombosis‑induced stroke in male C57/B6J mice. Behaviour 
      tests were performed at days 1, 3, 7, 14 and 28 post‑stroke. Infarct volume was 
      measured using Nissl staining at day 7 post‑stroke. Neurogenesis and angiogenesis 
      were evaluated by co‑labelling bromodeoxyuridine (BrdU) with doublecortin (DCX), 
      neuronal nuclei (NeuN) and von Willebrand factor, in immunohistochemical studies. 
      Brain‑derived neurotrophic factor (BDNF) and vascular endothelial growth factor 
      (VEGF) levels in the ipsilesional brain at day 28 post‑stroke were detected by 
      western blot analysis. Delayed administration of GUO did not reduce infarct 
      volume or affect neurological function at day 7 post‑stroke; however, it did 
      improve functional recovery from day 14 post‑stroke, when compared with the 
      vehicle group. GUO significantly increased the number of BrdU+ and BrdU+/DCX+ 
      cells in the subventricular zone and subgranular zone at all examined time 
      points, the number of Brdu+/NeuN+ cells in the peri‑infarction region at days 14 
      and 28 post‑stroke and microvessel density in the peri‑infarction region at day 
      28 post‑stroke compared with the vehicle group. In addition, the BDNF and VEGF 
      levels in the ipsilesional brain were significantly elevated. Delayed 
      administration of GUO at 24 h post‑stroke enhanced neurogenesis and angiogenesis, 
      and increased BDNF and VEGF levels, which likely contributes to long‑term 
      functional recovery following stroke.
FAU - Deng, Gang
AU  - Deng G
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
FAU - Qiu, Zhandong
AU  - Qiu Z
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
FAU - Li, Dayong
AU  - Li D
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
FAU - Fang, Yu
AU  - Fang Y
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
FAU - Zhang, Suming
AU  - Zhang S
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170427
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Dcx protein, mouse)
RN  - 0 (Doublecortin Protein)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Protective Agents)
RN  - 12133JR80S (Guanosine)
SB  - IM
MH  - Animals
MH  - Brain/metabolism/pathology
MH  - Brain Ischemia/complications/metabolism/pathology
MH  - Disease Models, Animal
MH  - Doublecortin Protein
MH  - Gene Expression
MH  - Guanosine/*administration & dosage
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Neovascularization, Physiologic/*drug effects
MH  - Nerve Growth Factors/genetics/metabolism
MH  - Neurogenesis/*drug effects
MH  - Protective Agents/administration & dosage
MH  - Recovery of Function/*drug effects
MH  - Stroke/drug therapy/etiology/*pathology/*physiopathology
MH  - Time Factors
PMC - PMC5436205
EDAT- 2017/05/11 06:00
MHDA- 2018/03/06 06:00
PMCR- 2017/04/27
CRDT- 2017/05/11 06:00
PHST- 2016/01/12 00:00 [received]
PHST- 2017/02/14 00:00 [accepted]
PHST- 2017/05/11 06:00 [pubmed]
PHST- 2018/03/06 06:00 [medline]
PHST- 2017/05/11 06:00 [entrez]
PHST- 2017/04/27 00:00 [pmc-release]
AID - mmr-15-06-3999 [pii]
AID - 10.3892/mmr.2017.6521 [doi]
PST - ppublish
SO  - Mol Med Rep. 2017 Jun;15(6):3999-4004. doi: 10.3892/mmr.2017.6521. Epub 2017 Apr 
      27.