| Title |
Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury
|
|---|---|
| Published in |
Molecular Neurobiology, October 2014
|
| DOI | 10.1007/s12035-014-8902-7 |
| Pubmed ID | |
| Authors |
Brandon P. Lucke-Wold, Aric F. Logsdon, Kelly E. Smith, Ryan C. Turner, Daniel L. Alkon, Zhenjun Tan, Zachary J. Naser, Chelsea M. Knotts, Jason D. Huber, Charles L. Rosen |
| Abstract |
Recent wars in Iraq and Afghanistan have accounted for an estimated 270,000 blast exposures among military personnel. Blast traumatic brain injury (TBI) is the 'signature injury' of modern warfare. Blood brain barrier (BBB) disruption following blast TBI can lead to long-term and diffuse neuroinflammation. In this study, we investigate for the first time the role of bryostatin-1, a specific protein kinase C (PKC) modulator, in ameliorating BBB breakdown. Thirty seven Sprague-Dawley rats were used for this study. We utilized a clinically relevant and validated blast model to expose animals to moderate blast exposure. Groups included: control, single blast exposure, and single blast exposure + bryostatin-1. Bryostatin-1 was administered i.p. 2.5 mg/kg after blast exposure. Evan's blue, immunohistochemistry, and western blot analysis were performed to assess injury. Evan's blue binds to albumin and is a marker for BBB disruption. The single blast exposure caused an increase in permeability compared to control (t = 4.808, p < 0.05), and a reduction back toward control levels when bryostatin-1 was administered (t = 5.113, p < 0.01). Three important PKC isozymes, PKCα, PKCδ, and PKCε, were co-localized primarily with endothelial cells but not astrocytes. Bryostatin-1 administration reduced toxic PKCα levels back toward control levels (t = 4.559, p < 0.01) and increased the neuroprotective isozyme PKCε (t = 6.102, p < 0.01). Bryostatin-1 caused a significant increase in the tight junction proteins VE-cadherin, ZO-1, and occludin through modulation of PKC activity. Bryostatin-1 ultimately decreased BBB breakdown potentially due to modulation of PKC isozymes. Future work will examine the role of bryostatin-1 in preventing chronic neurodegeneration following repetitive neurotrauma. |
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 Kingdom | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 2% |
| United States | 1 | 2% |
| Canada | 1 | 2% |
| Unknown | 59 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 14 | 23% |
| Researcher | 13 | 21% |
| Student > Doctoral Student | 8 | 13% |
| Student > Master | 6 | 10% |
| Student > Bachelor | 4 | 6% |
| Other | 10 | 16% |
| Unknown | 7 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 13 | 21% |
| Agricultural and Biological Sciences | 8 | 13% |
| Neuroscience | 6 | 10% |
| Nursing and Health Professions | 4 | 6% |
| Engineering | 4 | 6% |
| Other | 13 | 21% |
| Unknown | 14 | 23% |
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 13 October 2014.
All research outputs
#17,728,987
of 22,766,595 outputs
Outputs from Molecular Neurobiology
#2,314
of 3,441 outputs
Outputs of similar age
#172,163
of 255,616 outputs
Outputs of similar age from Molecular Neurobiology
#33
of 75 outputs
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So far Altmetric has tracked 3,441 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 28th percentile – i.e., 28% of its peers scored the same or lower than it.
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