| Title |
Profile of intravenous glyburide for the prevention of cerebral edema following large hemispheric infarction: evidence to date
|
|---|---|
| Published in |
Drug Design, Development and Therapy, August 2018
|
| DOI | 10.2147/dddt.s150043 |
| Pubmed ID | |
| Authors |
Zachary A King, Kevin N Sheth, W Taylor Kimberly, J Marc Simard |
| Abstract |
Glyburide (also known as glibenclamide) is a second-generation sulfonylurea drug that inhibits sulfonylurea receptor 1 (Sur1) at nanomolar concentrations. Long used to target KATP (Sur1-Kir6.2) channels for the treatment of diabetes mellitus type 2, glyburide was recently repurposed to target Sur1-transient receptor potential melastatin 4 (Trpm4) channels in acute central nervous system injury. Discovered nearly two decades ago, SUR1-TRPM4 has emerged as a critical target in stroke, specifically in large hemispheric infarction, which is characterized by edema formation and life-threatening brain swelling. Following ischemia, SUR1-TRPM4 channels are transcriptionally upregulated in all cells of the neurovascular unit, including neurons, astrocytes, microglia, oligodendrocytes and microvascular endothelial cells. Work by several independent laboratories has linked SUR1-TRPM4 to edema formation, with blockade by glyburide reducing brain swelling and death in preclinical models. Recent work showed that, following ischemia, SUR1-TRPM4 co-assembles with aquaporin-4 to mediate cellular swelling of astrocytes, which contributes to brain swelling. Additionally, recent work linked SUR1-TRPM4 to secretion of matrix metalloproteinase-9 (MMP-9) induced by recombinant tissue plasminogen activator in activated brain endothelial cells, with blockade of SUR1-TRPM4 by glyburide reducing MMP-9 and hemorrhagic transformation in preclinical models with recombinant tissue plasminogen activator. The recently completed GAMES (Glyburide Advantage in Malignant Edema and Stroke) clinical trials on patients with large hemispheric infarctions treated with intravenous glyburide (RP-1127) revealed promising findings with regard to brain swelling (midline shift), MMP-9, functional outcomes and mortality. Here, we review key elements of the basic science, preclinical experiments and clinical studies, both retrospective and prospective, on glyburide in focal cerebral ischemia and stroke. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 68 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Doctoral Student | 13 | 19% |
| Researcher | 8 | 12% |
| Student > Ph. D. Student | 7 | 10% |
| Other | 5 | 7% |
| Student > Master | 4 | 6% |
| Other | 9 | 13% |
| Unknown | 22 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 22 | 32% |
| Neuroscience | 9 | 13% |
| Biochemistry, Genetics and Molecular Biology | 5 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
| Immunology and Microbiology | 2 | 3% |
| Other | 3 | 4% |
| Unknown | 24 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 02 March 2023.
All research outputs
#7,479,510
of 25,707,225 outputs
Outputs from Drug Design, Development and Therapy
#496
of 2,278 outputs
Outputs of similar age
#119,515
of 342,850 outputs
Outputs of similar age from Drug Design, Development and Therapy
#14
of 69 outputs
Altmetric has tracked 25,707,225 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 2,278 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one has done well, scoring higher than 76% of its peers.
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We're also able to compare this research output to 69 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.