PMID- 31898187
OWN - NLM
STAT- MEDLINE
DCOM- 20210721
LR  - 20220127
IS  - 1868-601X (Electronic)
IS  - 1868-4483 (Linking)
VI  - 11
IP  - 4
DP  - 2020 Aug
TI  - Activation of the Hedgehog Pathway Promotes Recovery of Neurological Function 
      After Traumatic Brain Injury by Protecting the Neurovascular Unit.
PG  - 720-733
LID - 10.1007/s12975-019-00771-2 [doi]
AB  - The homeostasis of the neurovascular unit (NVU) is disrupted after traumatic 
      brain injury (TBI), and therapeutic strategies targeting the NVU would likely 
      improve neurological outcomes after TBI. Sonic Hedgehog (Shh), which is an 
      endogenous activator of the Hedgehog pathway, promotes brain repair in various 
      injuries. In this study, the controlled cortical impact (CCI) was used to 
      establish a moderate TBI model in adult male Sprague-Dawley rats (250-300 g), and 
      the NVU was reconstructed in vitro from the blood-brain barrier (BBB) and neurons 
      to investigate the effects of exogenous Shh protein on TBI. The modified 
      neurological severity scores (mNSS) and Morris water maze tests were used to 
      evaluate the effect of Shh on neurological function after TBI. The effect of Shh 
      on the NVU in vivo was evaluated by detecting the degrees of cerebral edema and 
      neuronal apoptosis. The integrity and permeability of the BBB, the level of 
      inflammatory factors, and the expression of apoptotic proteins were detected to 
      explore the effect of exogenous Shh on the NVU in vitro. The results showed that 
      exogenous Shh reduced cerebral edema and neuronal apoptosis and promoted 
      neurological recovery after TBI in rats. In vitro experiments showed that 
      Shh-induced activation of the Hedgehog pathway promoted stability of the NVU by 
      reducing damage to the tight junction structure and inhibiting the release of 
      inflammatory factors and neuron apoptosis. Based on these results, the 
      Shh-induced activation of the Hedgehog pathway might be a new promising treatment 
      for TBI.
FAU - Wu, Jingchuan
AU  - Wu J
AD  - Department of Neurosurgery, General Hospital of The YangTze River Shipping, Wuhan 
      Brain Hospital, Wuhan, 430014, Hubei, China.
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - He, Junchi
AU  - He J
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - Tian, Xiaocui
AU  - Tian X
AD  - College of Pharmacy, Chongqing Key Laboratory of Biochemistry and Molecular 
      Pharmacology, Chongqing Medical University, District of Yuzhong, Chongqing, 
      400016, China.
FAU - Zhong, Jianjun
AU  - Zhong J
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - Li, Hui
AU  - Li H
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - Sun, Xiaochuan
AU  - Sun X
AD  - Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China. sunxch1445@qq.com.
LA  - eng
GR  - 81571159/National Natural Science Foundation of China/International
GR  - 81801230/Young Scientists Fund/International
GR  - WX19Q17/Health and Family Planning Commission of Wuhan Municipality/International
GR  - WJ2019H364/Health and Family Planning Commission of Hubei Province/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200102
PL  - United States
TA  - Transl Stroke Res
JT  - Translational stroke research
JID - 101517297
RN  - 0 (Hedgehog Proteins)
RN  - 0 (SHH protein, human)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Blood-Brain Barrier/drug effects
MH  - Brain Edema/prevention & control
MH  - Brain Injuries, Traumatic/*metabolism/prevention & control
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Encephalitis/prevention & control
MH  - Hedgehog Proteins/*administration & dosage/*metabolism
MH  - Male
MH  - *Neurovascular Coupling/drug effects
MH  - Rats, Sprague-Dawley
MH  - *Recovery of Function
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - Hedgehog pathway
OT  - Inflammation
OT  - Neurovascular unit
OT  - Oxygen-glucose deprivation
OT  - Traumatic brain injury
EDAT- 2020/01/04 06:00
MHDA- 2021/07/22 06:00
CRDT- 2020/01/04 06:00
PHST- 2019/07/26 00:00 [received]
PHST- 2019/12/09 00:00 [accepted]
PHST- 2019/12/06 00:00 [revised]
PHST- 2020/01/04 06:00 [pubmed]
PHST- 2021/07/22 06:00 [medline]
PHST- 2020/01/04 06:00 [entrez]
AID - 10.1007/s12975-019-00771-2 [pii]
AID - 10.1007/s12975-019-00771-2 [doi]
PST - ppublish
SO  - Transl Stroke Res. 2020 Aug;11(4):720-733. doi: 10.1007/s12975-019-00771-2. Epub 
      2020 Jan 2.