blood-spinal cord barrier Archives - USF Health News https://hscweb3.hsc.usf.edu/blog/tag/blood-spinal-cord-barrier/ USF Health News Tue, 30 Apr 2019 21:27:00 +0000 en-US hourly 1 https://wordpress.org/?v=6.5.3 Transplanted bone marrow-derived endothelial progenitor cells delay ALS disease progression https://hscweb3.hsc.usf.edu/blog/2019/04/02/transplanted-endothelial-progenitor-cells-derived-from-bone-marrow-delay-als-disease-progression/ Tue, 02 Apr 2019 15:21:26 +0000 https://hscweb3.hsc.usf.edu/?p=27871 A new University of South Florida preclinical study finds that the regenerative cell therapy boosts motor nerve cell survival by repairing the blood-spinal cord barrier TAMPA, Fla. (April […]

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A new University of South Florida preclinical study finds that the regenerative cell therapy boosts motor nerve cell survival by repairing the blood-spinal cord barrier

TAMPA, Fla. (April 2, 2019) — Transplantation of human bone marrow-derived endothelial progenitor cells (EPCs) into mice mimicking symptoms of amyotrophic lateral sclerosis (ALS) helped more motor neurons survive and slowed disease progression by repairing damage to the blood-spinal cord barrier (BSCB), University of South Florida researchers report.

The study was published March 27 in Scientific Reports, one of the Nature journals. The findings contribute to a growing body of work exploring cell therapy approaches to barrier repair in ALS and other neurodegenerative diseases.

Human bone marrow-derived endothelial progenitor cells in vitro

The progressive degeneration of nerve cells that control muscle movement (motor neurons) eventually leads to total paralysis and death from ALS. Each day, an average of 15 Americans are diagnosed with the disease, according to the ALS Association.

Damage to the barrier between the blood circulatory system and the central nervous system has been recognized as a key factor in the development of ALS. A breach in this protective wall opens the brain and spinal cord to immune/inflammatory cells and other potentially harmful substances circulating in peripheral blood. The cascade of biochemical events leading to ALS includes alterations of endothelial cells lining the inner surface of tiny blood vessels near damaged spinal cord motor neurons.

This latest study by lead author Svitlana Garbuzova-Davis, PhD, and colleagues at the USF Health Morsani College of Medicine’s Center of Excellence for Aging & Brain Repair, builds upon a previous study showing that human bone marrow-derived stem cells improved motor functions and nervous system conditions in symptomatic ALS mice by advancing barrier repair. However, in that earlier USF study the beneficial effect was delayed until several weeks after cell transplant and some severely damaged capillaries were detected even after a high-dose treatment. So in this study, the researchers tested whether human EPCs – cells harvested from bone marrow but more genetically similar to vascular endothelial cells than undifferentiated stem cells – would provide even better BSCB restoration.

Svitlana Garbuzova-Davis, PhD

ALS mice were intravenously administered a dose of human bone-marrow derived EPCs.  Four weeks after transplant, the results of the active cell treatment was compared against findings from two other groups of mice:  ALS mice receiving a media (saline) treatment and untreated healthy mice.

The symptomatic ALS mice receiving EPC treatments demonstrated significantly improved motor function, increased motor neuron survival and slower disease progression than their symptomatic counterparts injected with media. The researchers suggest that these benefits leading to BSCB repair may have been promoted by widespread attachment of EPCs to capillaries in the spinal cord. To support this proposal, they point to evidence of substantially restored capillaries, less capillary leakage, and re-establishment of structural support cells (perivascular astrocytes) that play a role in helping form a protective barrier in the spinal cord and brain.

Further research is needed to clearly define the mechanisms of EPC barrier repair.  But, the study authors conclude: “From a translational viewpoint, the initiation of cell treatment at the symptomatic disease stage offered robust restoration of BSCB integrity and shows promise as a future clinical therapy for ALS.”

The USF study was supported by a grant from the National Institute of Neurological Disorders and Stroke.

Article citation:
Svitlana Garbuzova-Davis, Crupa Kurien, Edward Haller, David J. Eve, Stephanie Navarro, George Steiner, Ajay Mahendrasah, Surafuale Hailu, Mohammed Khatib, Kayla J. Boccio, Cesario V. Borlongan, Harry R. Van Loveren, Stanley H. Appel and Paul R. Sanberg. Human Bone Marrow Endothelial Progenitor Cell Transplantation into Symptomatic ALS Mice Delays Disease Progression and Increases Motor Neuron Survival by Repairing Blood-Spinal Cord Barrier, Scientific Reports, March 27, 2019. https://doi.org/10.1038/s41598-019-41747-4.



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USF study shows stem cell transplants may advance ALS treatment by repair of blood-spinal cord barrier https://hscweb3.hsc.usf.edu/blog/2017/05/12/usf-study-shows-stem-cell-transplants-may-advance-als-treatment-repair-blood-spinal-cord-barrier/ Fri, 12 May 2017 14:59:31 +0000 https://hscweb3.hsc.usf.edu/?p=22127 ALS mice improved with stem cell therapy; first step for science in finding better treatment   TAMPA, Fla. (May 12, 2017) – Researchers at the University of South […]

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ALS mice improved with stem cell therapy; first step for science in finding better treatment  

TAMPA, Fla. (May 12, 2017) – Researchers at the University of South Florida show in a new study that bone marrow stem cell transplants helped improve motor functions and nervous system conditions in mice with the disease amyotrophic lateral sclerosis (ALS) by repairing damage to the  blood-spinal cord barrier.

In a study recently published in the journal Scientific Reports, researchers in USF’s Center of Excellence for Aging and Brain Repair say the results of their experiment are an early step in pursuing stem cells for potential repair of the blood-spinal cord barrier, which has been identified as key in the development of ALS. USF Health Professor Svitlana Garbuzova-Davis, PhD, led the project.

Previous studies in development of various therapeutic approaches for ALS typically used pre-symptomatic mice. This is the first study advancing barrier repair that treats symptomatic mice, which more closely mirrors conditions for human patients, Dr. Garbuzova-Davis said.

Svitlana Garbuzova-Davis, PhD, led the study.

Using stem cells harvested from human bone marrow, researchers transplanted cells into mice modeling ALS and already showing disease symptoms. The transplanted stem cells differentiated and attached to vascular walls of many capillaries, beginning the process of blood-spinal cord barrier repair.

The stem cell treatment delayed the progression of the disease and led to improved motor function in the mice, as well as increased motor neuron cell survival, the study reported.

ALS is a progressive neurodegenerative disease that affects neuronal cells in the brain and the spinal cord, which send signals to control muscles throughout the body. The progressive degeneration of motor neuron cells leads to death from ALS. More than 6,000 Americans each year are diagnosed with the disease.

Because stem cells have the ability to develop into many different cell types in the body, researchers at USF’s Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair have focused on using stem cells to restore function lost through neurodegenerative disorders or injuries.

Damage to the barrier between the blood circulatory system and the central nervous system has been recently recognized as a factor in ALS development, leading researchers to work on targeting the barrier for repair as a potential strategy for ALS therapy.

In this study, the ALS mice were given intravenous treatments of one of three different doses of the bone marrow stem cells. Four weeks after treatment, the scientists determined improved motor function and enhanced motor neuron survival. The mice receiving the higher doses of stem cells fared better in the study, the researcher noted.

The transplanted stem cells had differentiated into endothelial cells – which form the inner lining of a blood vessel, providing a barrier between blood and spinal cord tissue – and attached to capillaries in the spinal cord. Furthermore, the researchers observed reductions in activated glial cells, which contribute to inflammatory processes in ALS.

USF Health Morsani College of Medicine researchers Crupa Kurien, Avery Thomson, Dimitri Falco, Sohaib Ahmad, Joseph Staffetti, George Steiner, Sophia Abraham, Greeshma James, Ajay Mahendrasah, Paul R. Sanberg and Cesario V. Borlongan joined in the project. The study was funded by the National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Read the full study here.

                                                                                                                                                     -USF Health-
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, the Biomedical Sciences Graduate and Postdoctoral Programs, and the USF Physicians Group. The University of South Florida, established in 1956 and located in Tampa, is a high-impact, global research university dedicated to student success. USF is ranked in the Top 30 nationally for research expenditures among public universities, according to the National Science Foundation. For more information, visit www.health.usf.edu

News release by Vickie Chachere, USF Research and Innovation

Media contact: 
Anne DeLotto Baier, USF Health Communications
abaier@health.usf.edu or (813) 974-3303



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USF researchers find stroke damages blood-spinal cord barrier https://hscweb3.hsc.usf.edu/blog/2016/06/15/usf-researchers-find-stroke-damages-blood-spinal-cord-barrier/ Wed, 15 Jun 2016 23:43:25 +0000 https://hscweb3.hsc.usf.edu/?p=18866 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) […]

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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.”

Garbuzova_Davis_400x400

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.

-USF Health-
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, the Biomedical Sciences Graduate and Postdoctoral Programs, and the USF Physicians Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit www.health.usf.edu

– News release by Randy Fillmore, USF Communications and Marketing



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