scholarly journals Immunomodulation with Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis

2019 ◽  
Vol 28 (7) ◽  
pp. 864-873 ◽  
Author(s):  
Maple L. Shiao ◽  
Ce Yuan ◽  
Andrew T. Crane ◽  
Joseph P. Voth ◽  
Mario Juliano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Injury ◽  
Umbilical Cord Blood ◽  
Ischemic Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Brain Transcriptome ◽  
Blood Stem Cells ◽  
Cord Blood Stem Cells ◽  
The Brain

Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that were significantly differentially expressed after ischemic injury compared with control brains. Following UCBSC treatment, 220 of the 275 differentially expressed genes returned to normal levels. Detailed analysis of these altered transcripts revealed that the vast majority were associated with activation of the immune system following cerebral ischemia which were normalized following UCBSC therapy. Major alterations in gene expression profiles after ischemia include blood-brain-barrier breakdown, cytokine production, and immune cell infiltration. These results suggest that UCBSC protect the brain following ischemic injury by down regulating the aberrant activation of innate and adaptive immune responses.

scholarly journals Amelioration of Ischemic Brain Injury in Rats with Human Umbilical Cord Blood Stem Cells: Mechanisms of Action

2016 ◽  
Vol 25 (8) ◽  
pp. 1473-1488 ◽  
Author(s):  
Laura L. Hocum Stone ◽  
Feng Xiao ◽  
Jessica Rotschafer ◽  
Zhenhong Nan ◽  
Mario Juliano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Injury ◽  
Umbilical Cord Blood ◽  
Mechanisms Of Action ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Blood Stem Cells ◽  
Cord Blood Stem Cells

scholarly journals Electroacupuncture increased cerebral blood flow and reduced ischemic brain injury: dependence on stimulation intensity and frequency

2011 ◽  
Vol 111 (6) ◽  
pp. 1877-1887 ◽  
Author(s):  
Fei Zhou ◽  
Jingchun Guo ◽  
Jieshi Cheng ◽  
Gencheng Wu ◽  
Ying Xia
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Stimulation Parameters ◽  
Cerebral Artery Occlusion ◽  
The Brain

Stroke causes ischemic brain injury and is a leading cause of neurological disability and death. There is, however, no promising therapy to protect the brain from ischemic stress to date. Here we show an exciting finding that optimal electroacupuncture (EA) effectively protects the brain from ischemic injury. The experiments were performed on rats subjected to middle cerebral artery occlusion (MCAO) with continuous monitoring of cerebral blood flow. EA was delivered to acupoints of “Shuigou” (Du 26) and “Baihui” (Du 20) with different intensities and frequencies to optimize the stimulation parameters. The results showed that 1) EA at 1.0–1.2 mA and 5–20 Hz remarkably reduced ischemic infarction, neurological deficit, and death rate; 2) the EA treatment increased the blood flow by >100%, which appeared immediately after the initiation of EA and disappeared after the cessation of EA; 3) the EA treatment promoted the recovery of the blood flow after MCAO; 4) “nonoptimal” parameters of EA (e.g., <0.6 mA or >40 Hz) could not improve the blood flow or reduce ischemic injury; and 5) the same EA treatment with optimal parameters could not increase the blood flow in naive brains. These novel observations suggest that appropriate EA treatment protects the brain from cerebral ischemia by increasing blood flow to the ischemic brain region via a rapid regulation. Our findings have far-reaching impacts on the prevention and treatment of ischemic encephalopathy, and the optimized EA parameters may potentially be a useful clue for the clinical application of EA.

scholarly journals CURRENT CONCEPTS OF PERINATAL ISCHEMIC INJURY IN THE BRAIN NEUROVASCULAR UNIT: MOLECULAR TARGETS FOR NEUROPROTECTION

2013 ◽  
Vol 68 (12) ◽  
pp. 26-35 ◽  
Author(s):  
A. V. Morgun ◽  
N. V. Kuvacheva ◽  
T. E. Taranushenko ◽  
E. D. Khilazhieva ◽  
N. A. Malinovskaya ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neurovascular Unit ◽  
Cell Communication ◽  
Molecular Targets ◽  
Ischemic Injury ◽  
Ischemic Brain Injury ◽  
Perinatal Brain Injury ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury ◽  
The Brain

Perinatal hypoxic-ischemic brain injury is a relevant medical and social problem. Among many pathological processes in the neonatal period perinatal hypoxic-ischemic injury is a major cause of further hemorrhage, necrotic and atrophic changes in the brain.  This review presents recent data on the basic mechanisms of the hypoxic-ischemic brain injury along the concept of neurovascular unit (neurons, astrocytes, endothelial cells, pericytes) with the focus on alterations in cell-to-cell communication. Pathological changes caused by ischemia-hypoxia are considered within two phases of injury (ischemic phase and reperfusion phase). The review highlights changes in each individual component of the neurovascular unit and their interactions. Molecular targets for pharmacological improvement of intercellular communication within neurovascular unit as a therapeutic strategy in perinatal brain injury are discussed. 

scholarly journals From cord to caudate: characterizing umbilical cord blood stem cells and their paracrine interactions with the injured brain

2017 ◽  
Vol 83 (1-2) ◽  
pp. 205-213 ◽  
Author(s):  
Priya F Maillacheruvu ◽  
Lauren M Engel ◽  
Isaiah T Crum ◽  
Devendra K Agrawal ◽  
Eric S Peeples
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Injured Brain ◽  
Blood Stem Cells ◽  
Cord Blood Stem Cells

scholarly journals Optimizing Stem Cell Therapy after Ischemic Brain Injury

2020 ◽  
Vol 22 (3) ◽  
pp. 286-305 ◽  
Author(s):  
Shuai Zhang ◽  
Brittany Bolduc Lachance ◽  
Bilal Moiz ◽  
Xiaofeng Jia
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Cardiac Arrest ◽  
Stem Cell ◽  
Brain Injury ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Injury Treatment

Stem cells have been used for regenerative and therapeutic purposes in a variety of diseases. In ischemic brain injury, preclinical studies have been promising, but have failed to translate results to clinical trials. We aimed to explore the application of stem cells after ischemic brain injury by focusing on topics such as delivery routes, regeneration efficacy, adverse effects, and in vivo potential optimization. PUBMED and Web of Science were searched for the latest studies examining stem cell therapy applications in ischemic brain injury, particularly after stroke or cardiac arrest, with a focus on studies addressing delivery optimization, stem cell type comparison, or translational aspects. Other studies providing further understanding or potential contributions to ischemic brain injury treatment were also included. Multiple stem cell types have been investigated in ischemic brain injury treatment, with a strong literature base in the treatment of stroke. Studies have suggested that stem cell administration after ischemic brain injury exerts paracrine effects via growth factor release, blood-brain barrier integrity protection, and allows for exosome release for ischemic injury mitigation. To date, limited studies have investigated these therapeutic mechanisms in the setting of cardiac arrest or therapeutic hypothermia. Several delivery modalities are available, each with limitations regarding invasiveness and safety outcomes. Intranasal delivery presents a potentially improved mechanism, and hypoxic conditioning offers a potential stem cell therapy optimization strategy for ischemic brain injury. The use of stem cells to treat ischemic brain injury in clinical trials is in its early phase; however, increasing preclinical evidence suggests that stem cells can contribute to the down-regulation of inflammatory phenotypes and regeneration following injury. The safety and the tolerability profile of stem cells have been confirmed, and their potent therapeutic effects make them powerful therapeutic agents for ischemic brain injury patients.

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