| Title |
Inhibition of Toll-Like Receptor-4 (TLR-4) Improves Neurobehavioral Outcomes After Acute Ischemic Stroke in Diabetic Rats: Possible Role of Vascular Endothelial TLR-4
|
|---|---|
| Published in |
Molecular Neurobiology, June 2018
|
| DOI | 10.1007/s12035-018-1184-8 |
| Pubmed ID | |
| Authors |
Yasir Abdul, Mohammed Abdelsaid, Weiguo Li, R. Clinton Webb, Jennifer C. Sullivan, Guangkuo Dong, Adviye Ergul |
| Abstract |
Diabetes increases the risk of occurrence and poor functional recovery after ischemic stroke injury. Previously, we have demonstrated greater hemorrhagic transformation (HT), edema, and more severe functional deficits after stroke in diabetic animals that also presented with cerebral vasoregression and endothelial cell death in the recovery period. Given that Toll-like receptor 4 (TLR-4) activation in microvascular endothelial cells triggers a robust inflammatory response, we hypothesized that inhibition of TLR-4 signaling prevents endothelial cell death and improves outcomes after stroke. Animals were treated with vehicle or TLR-4 inhibitor TAK242 (3 mg/kg; i.p.) following middle cerebral artery occlusion (MCAO). Neurobehavioral deficits were measured at baseline and day 3 after ischemic stroke. Primary brain microvascular endothelial cells (BMVECs) from diabetic animals were subjected to oxygen glucose deprivation re-oxygenation (OGDR) and treated with 0.1 mM iron(III)sulfate hydrate (iron) (to mimic the post-stroke bleeding) and TLR-4 inhibitors. Ischemic stroke increased the expression of TLR-4 in both hemispheres and in the microvasculature of diabetic animals. Cerebral infarct, edema, HT, and functional deficits were greater in diabetic compared to control animals. Inhibition of TLR-4 significantly reduced the neurovascular injury and improved functional outcomes. OGDR and iron reduced the cell viability and increased the expression of TLR-4 associated proteins (RIP3, MyD88, phospho-NF-kB, and release of IL-6) in BMVECs from diabetic animals. In conclusion, TLR-4 is highly upregulated in the microvasculature and that beneficial effects of TLR-4 inhibition are more profound in diabetes. This suggests that inhibition of vascular TLR-4 may provide therapeutic benefits for stroke recovery in diabetes. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 32 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 5 | 16% |
| Student > Master | 4 | 13% |
| Student > Ph. D. Student | 3 | 9% |
| Student > Postgraduate | 2 | 6% |
| Researcher | 2 | 6% |
| Other | 5 | 16% |
| Unknown | 11 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 25% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 13% |
| Biochemistry, Genetics and Molecular Biology | 4 | 13% |
| Neuroscience | 2 | 6% |
| Veterinary Science and Veterinary Medicine | 1 | 3% |
| Other | 5 | 16% |
| Unknown | 8 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 24 June 2018.
All research outputs
#14,882,474
of 23,092,602 outputs
Outputs from Molecular Neurobiology
#1,944
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Outputs of similar age
#179,929
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Outputs of similar age from Molecular Neurobiology
#69
of 130 outputs
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