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Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury
Journal article   Open access   Peer reviewed

Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury

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, …
Molecular neurobiology, v 52(3), pp 1119-1134
Dec 2015
DOI: https://doi.org/10.1007/s12035-014-8902-7
PMID: 25301233
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc5000781View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Animals Antigens, CD - metabolism Astrocytes - enzymology Blast Injuries - drug therapy Blast Injuries - physiopathology Blood-Brain Barrier - drug effects Brain Injuries - drug therapy Brain Injuries - physiopathology Bryostatins - pharmacology Bryostatins - therapeutic use Cadherins - metabolism Endothelial Cells - drug effects Endothelial Cells - enzymology Endothelial Cells - physiology Male Occludin - metabolism Prefrontal Cortex - blood supply Protein Kinase C-alpha - antagonists & inhibitors Protein Kinase C-alpha - metabolism Protein Kinase C-delta - metabolism Protein Kinase C-epsilon - drug effects Protein Kinase C-epsilon - metabolism Rats Rats, Sprague-Dawley Tight Junctions - drug effects Zonula Occludens-1 Protein - metabolism
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.

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55 citations in Web of Science
60 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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