Quan Hu, Tong Li, Lingxiao Wang, Yunkai Xie, Song Liu, Xuemei Bai, Tiantian Zhang, Shishi Bo, Danqing Xin, Hao Xue, Gang Li, Zhen Wang
Abstract
The sonic hedgehog (Shh) signaling pathway plays a fundamental role in the central nervous system (CNS) development, but its effects on neural cell survival and brain repair after subarachnoid hemorrhage (SAH) has not been well-investigated. The present study was undertaken to evaluate the influence of an agonist of the Shh co-receptor Smoothened (Smo), purmorphamine (PUR), on early brain injury (EBI) as well as the underlying mechanisms after SAH. PUR was administered via an intraperitoneal injection with a dose of 0.5, 1, and 5 mg/kg at 2, 6, 24, and 46 h after SAH in rat model. The results showed that PUR treatment significantly ameliorated brain edema, improved neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex (PFC), associated with a decrease in Bax/Bcl-2 ratio and suppression of caspase-3 activation at 48 h after SAH. PUR also promoted phospho-ERK levels. Additionally, PUR treatment markedly decreased MDA concentration accompanied with the elevation in the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in PFC. Notably, PUR treatment significantly reversed the changes of Shh pathway mediators containing Patched, Gli1, and Shh by SAH insult, and the neuroprotection of PUR on SAH was blocked by Smo antagonist cyclopamine. These results indicated that PUR exerts neuroprotection against SAH-evoked injury in rats, mediated in part by anti-apoptotic and anti-oxidant mechanism, up-regulating phospho-ERK levels, mediating Shh signaling molecules in the PFC.
Pharmacology, Toxicology and Pharmaceutical Science
2
7%
Neuroscience
2
7%
Other
2
7%
Unknown
8
30%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 January 2017.
All research outputs
#19,939,131
of 25,375,376 outputs
Outputs from Frontiers in Cellular Neuroscience
#3,267
of 4,689 outputs
Outputs of similar age
#307,872
of 430,749 outputs
Outputs of similar age from Frontiers in Cellular Neuroscience
#48
of 89 outputs
Altmetric has tracked 25,375,376 research outputs across all sources so far. This one is in the 18th percentile – i.e., 18% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,689 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 23rd percentile – i.e., 23% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 430,749 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 24th percentile – i.e., 24% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 89 others from the same source and published within six weeks on either side of this one. This one is in the 25th percentile – i.e., 25% of its contemporaries scored the same or lower than it.
