Stroke’s long-term effects on blood-spinal cord barrier can lead to ‘an increasingly toxic environment’ in spinal cord and ‘significant input on disease pathology’

Tampa, Fla. (June 14, 2016) – A team of researchers at the University of South Florida investigating the short and long-term effects of ischemic stroke in a rodent model has found that stroke can cause long-term damage to the blood-spinal cord barrier (BSCB), creating a “toxic environment” in the spinal cord that might leave stroke survivors susceptible to motor dysfunction and disease pathology.

The paper describing their study was recently published online and will appear in an upcoming issue of Journal of Neuropathology and Experimental Neurology.

“This study, carried out using laboratory rats modeling stroke, demonstrated that ischemic stroke — in both its subacute and chronic stages — damages the BSCB in a variety of ways, creating a toxic environment in the spinal cord that can lead to further disability and exacerbate disease pathology,” said study lead author Svitlana Garbuzova-Davis, PhD, associate professor in USF’s Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair. “The aim of our study was to evaluate post-stroke BSCB condition that might lead to the development of more effective therapies for stroke survivors.”

Svitlana Garbuzova-Davis, PhD

The BSCB provides a specialized protective ‘microenvironment’ for neural cells in the spinal cord. Substantial vascular damage is a major pathologic feature of both subacute and chronic stroke caused by an extended period of microvascular permeability after the BSCB loses integrity. Damage to the BSCB, explained the researchers, plays a fundamental role in the development of several pathological conditions, including abnormal motor function.

The researchers, who evaluated the BSCB in test animals at seven and 30 days after stroke modeling, found that ischemic stroke damaged the gray and white matter in the cervical spinal cord on both sides of the spinal column, based on analysis of electron microscope images. Among the effects were damage to neural cells called ‘astrocytes,’ loss of motor neurons, reduced integrity of a tight junction protein between barrier cells, and swollen axons with damaged myelin in ascending and descending tracts connecting to the brain.

They also found stroke-associated ‘upregulation’ of Beclin-1 in endothelial cells composing the BSCB. Beclin-1, explained the researchers, helps induce autophagy, an activity associated with removal of various intracellular components. They also observed a decrease in LC3B, an essential autophagy protein, at a later stage post-stroke. These observations of Beclin-1 and LC3B suggest an impaired post-stroke autophagy process in spinal cord capillaries, inducing endothelial cell degeneration.

These stroke-related alterations in the cervical spinal cord indicate pervasive and long-lasting BSCB damage that would severely affect spinal cord function, wrote the researchers, adding that the widespread microvascular impairment in the gray and white matter of the cervical spinal cord aggravated motor neuron deterioration and had the potential to cause motor dysfunction.

“Because our investigations on the post-stroke microvascular alterations, including BSCB damage, have just begun, many questions remain,” said senior author Cesario Borlongan, PhD, professor and director of the USF Center of Excellence for Aging and Brain Repair. “Specifically, the protein expression responsible for endothelial cell degeneration and tight junction damage we identified in this study needs to be confirmed through further tests. Also, behavioral tests of motor function in post-stroke animals in correlation with BSCB damage are needed. These questions and others will be addressed in our future studies.”

Paul R. Sanberg, PhD, DSc, Distinguished University Professor, a co-author of the paper, concluded that “these novel data showing BSCB damage in subacute and chronic ischemic stroke may lead to development of new therapeutic approaches for patients with ischemic cerebral infarction.”

Article citation:
Blood-Spinal Cord Barrier Alterations in Subacute and Chronic Stages of a Rat Model of Focal Cerebral Ischemia. Svitlana Garbuzova-Davis; Edward Haller; Naoki Tajiri; Avery Thomson; Jennifer Barretta; Stephanie N. Williams; Eithan D. Haim; Hua Qin; Aric Frisina-Deyo; Jerry V. Abraham; Paul R. Sanberg; Harry Van Loveren; Cesario V. Borlongan. Journal of Neuropathology & Experimental Neurology 2016; doi: 10.1093/jnen/nlw040.

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New demands on universities go beyond research and teaching to basic research and technology transfer, NAI paper says

Tampa, FL  (April 28, 2014) —  Should universities change their faculty tenure and promotion calculus based on research and publication to one that recognizes and includes faculty research activities that translate into patents, licensing and commercialization of products?

“Yes,” say a group of university officials from across the nation whose paper “Changing the academic culture: Valuing patents and commercialization toward tenure and career advancement” is published in the current issue of The Proceedings of the National Academy of Sciences.

USF’s Paul R. Sanberg is lead author of the NAI paper

“Over the past several decades, university missions have expanded from teaching and research to include economic development and translating university-based research into real products that benefit society,” says paper lead author Paul R. Sanberg, Distinguished University Professor and senior vice president for research and innovation at the University of South Florida (USF), and president of the National Academy of Inventors (NAI).

Dr. Sanberg is also executive director of the Center of Excellence for Aging and Brain Repair at the USF Health Morsani College of Medicine.

The authors — from USF, the California Institute of Technology, the University of Delaware, the University of Minnesota, The University of Alabama at Birmingham, Purdue University, and the University of Missouri St. Louis — say that, while research activities that translate to product commercialization should not replace traditional scholarly pursuits such as teaching, mentoring students and publishing research, patent and commercialization activities should be considered equally in decisions related to faculty tenure and academic advancement.

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