PMID- 29563509
OWN - NLM
STAT- MEDLINE
DCOM- 20190926
LR  - 20190926
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Mar 21
TI  - Neuroprotective effect of dexmedetomidine in a murine model of traumatic brain 
      injury.
PG  - 4935
LID - 10.1038/s41598-018-23003-3 [doi]
LID - 4935
AB  - No FDA approved pharmacological therapy is available that would reduce cell death 
      following traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly 
      selective agonist of alpha-2 adrenergic receptors and has demonstrated 
      neuroprotective effects in hippocampal slice cultures undergoing direct impact. 
      However, no one has tested whether Dex, in addition to its sedative action, has 
      neuroprotective effects in an animal model of TBI. Thus, in the present study, we 
      investigated the effects of Dex on an animal model of TBI. Mice received 
      different doses of Dex (1, 10, or 100 microg/kg bodyweight, n = 10 each group) or 
      saline as control at 1 hour and 12 hours following TBI. The mice treated with Dex 
      lost less cortical tissue than the control mice. Further analysis found that Dex 
      treatment reduced cell death in the cortex and the hippocampus measured by 
      Fluoro-Jade B (FJB) staining, prevented axonal degeneration detected by 
      immunostaining with antibody against beta-amyloid precursor protein (beta-APP), and 
      protected synapses from elimination with synaptophysin staining. Taken together, 
      in an in vivo murine model of TBI, Dex at the dose of 100 microg/kg not only 
      prevented tissue lesion and cell death, but also reduced axonal injury and 
      synaptic degeneration caused by TBI.
FAU - Wu, Jin
AU  - Wu J
AD  - Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen 
      University, Zhangzhou, China.
FAU - Vogel, Todd
AU  - Vogel T
AD  - Department of Neurosurgery, Indiana University, Indianapolis, IN, USA.
FAU - Gao, Xiang
AU  - Gao X
AD  - Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research 
      Institute, Indianapolis, IN, USA.
FAU - Lin, Bin
AU  - Lin B
AD  - Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen 
      University, Zhangzhou, China.
FAU - Kulwin, Charles
AU  - Kulwin C
AD  - Department of Neurosurgery, Indiana University, Indianapolis, IN, USA.
FAU - Chen, Jinhui
AU  - Chen J
AD  - Department of Neurosurgery, Indiana University, Indianapolis, IN, USA. 
      chen204@iupui.edu.
AD  - Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research 
      Institute, Indianapolis, IN, USA. chen204@iupui.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180321
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Neuroprotective Agents)
RN  - 67VB76HONO (Dexmedetomidine)
SB  - IM
MH  - Animals
MH  - *Brain Injuries, Traumatic/drug therapy/metabolism/pathology
MH  - *Cerebral Cortex/metabolism/pathology
MH  - Dexmedetomidine/*pharmacology
MH  - Disease Models, Animal
MH  - *Hippocampus/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Neuroprotective Agents/*pharmacology
PMC - PMC5862953
COIS- The authors declare no competing interests.
EDAT- 2018/03/23 06:00
MHDA- 2019/09/27 06:00
PMCR- 2018/03/21
CRDT- 2018/03/23 06:00
PHST- 2016/11/07 00:00 [received]
PHST- 2018/03/05 00:00 [accepted]
PHST- 2018/03/23 06:00 [entrez]
PHST- 2018/03/23 06:00 [pubmed]
PHST- 2019/09/27 06:00 [medline]
PHST- 2018/03/21 00:00 [pmc-release]
AID - 10.1038/s41598-018-23003-3 [pii]
AID - 23003 [pii]
AID - 10.1038/s41598-018-23003-3 [doi]
PST - epublish
SO  - Sci Rep. 2018 Mar 21;8(1):4935. doi: 10.1038/s41598-018-23003-3.