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Clinical Cell Therapy Guidelines For Neurorestoration (Ianr/Canr 2017), Hongyun Huang, Wise Young, Lin Chen, Shiqing Feng, Ziad M. Zoubi, Hari Shanker Sharma, Hooshang Saberi, Gustavo A. Moviglia, Xijing He, Dafin F. Muresanu, Alok Sharma, Ali Otom, Russell J. Andrews, Adeeb Al-Zoubi, Andrey S. Bryukhovetskiy, Elena R. Chernykh, Krystyna Domańska-Janik, Emad Jafar, W. Eustace Johnson, Ying Li, Daqing Li, Zuo Luan, Gengsheng Mao, Ashok K. Shetty, Dario Siniscalco, Stephen Skaper, Tiansheng Sun, Yunliang Wang, Lars Wiklund, Qun Xue, Si-Wei You, Zuncheng Zheng, Milan R. Dimitrijevic, W. S. Masri, Paul R. Sanberg Jan 2022

Clinical Cell Therapy Guidelines For Neurorestoration (Ianr/Canr 2017), Hongyun Huang, Wise Young, Lin Chen, Shiqing Feng, Ziad M. Zoubi, Hari Shanker Sharma, Hooshang Saberi, Gustavo A. Moviglia, Xijing He, Dafin F. Muresanu, Alok Sharma, Ali Otom, Russell J. Andrews, Adeeb Al-Zoubi, Andrey S. Bryukhovetskiy, Elena R. Chernykh, Krystyna Domańska-Janik, Emad Jafar, W. Eustace Johnson, Ying Li, Daqing Li, Zuo Luan, Gengsheng Mao, Ashok K. Shetty, Dario Siniscalco, Stephen Skaper, Tiansheng Sun, Yunliang Wang, Lars Wiklund, Qun Xue, Si-Wei You, Zuncheng Zheng, Milan R. Dimitrijevic, W. S. Masri, Paul R. Sanberg

Neurosurgery and Brain Repair Faculty Publications

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version “Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)”. The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and …


Improving Neurorepair In Stroke Brain Through Endogenous Neurogenesis-Enhancing Drugs, Kuo-Jen Wu, Seongjin Yu, Jea-Young Lee, Barry Hoffer, Yun Wang Jan 2022

Improving Neurorepair In Stroke Brain Through Endogenous Neurogenesis-Enhancing Drugs, Kuo-Jen Wu, Seongjin Yu, Jea-Young Lee, Barry Hoffer, Yun Wang

Neurosurgery and Brain Repair Faculty Publications

Stroke induces not only cell death but also neurorepair. De novo neurogenesis has been found in the subventricular zone of the adult mammalian brain days after stroke. Most of these newly generated cells die shortly after the insult. Recent studies have shown that pharmacological manipulation can improve the survival of endogenous neuroprogenitor cells and neural regeneration in stroke rats. As these drugs target the endogenous reparative processes that occur days after stroke, they may provide a prolonged window for stroke therapy. Here, we discuss endogenous neurogenesis-enhancing drugs and review the general status of stroke therapeutics in evaluating the field of …


Neuroprotective Effects Of Human Amniotic Fluid Stem Cells-Derived Secretome In An Ischemia/Reperfusion Model, Vanessa Castelli, Ivana Antonucci, Michele D'Angelo, Alessandra Tessitore, Veronica Zelli, Elisabetta Benedetti, Claudio Ferri, Giovambattista Desideri, Cesar Borlongan, Liborio Stuppia, Annamaria Cimini Jan 2021

Neuroprotective Effects Of Human Amniotic Fluid Stem Cells-Derived Secretome In An Ischemia/Reperfusion Model, Vanessa Castelli, Ivana Antonucci, Michele D'Angelo, Alessandra Tessitore, Veronica Zelli, Elisabetta Benedetti, Claudio Ferri, Giovambattista Desideri, Cesar Borlongan, Liborio Stuppia, Annamaria Cimini

Neurosurgery and Brain Repair Faculty Publications

Stem cells offer the basis for the promotion of robust new therapeutic approaches for a variety of human disorders. There are still many limitations to be overcome before clinical therapeutic application, including a better understanding of the mechanism by which stem cell therapies may lead to enhanced recovery. In vitro investigations are necessary to dissect the mechanisms involved and to support the potential development in stem cell-based therapies. In spite of growing interest in human amniotic fluid stem cells, not much is known about the characteristics of their secretome and regarding the potential neuroprotective mechanism in different pathologies, including stroke. …


Foraminal Ligaments Tether Upper Cervical Nerve Roots: A Potential Cause Of Postoperative C5 Palsy, Andrew S. Jack, Brooks R. Osburn, Zane A. Tymchak, Wyatt L. Ramey, Rod J. Oskouian, Robert A. Hart, Jens R. Chapman, Line G. Jacques, R. Shane Tubbs Jan 2020

Foraminal Ligaments Tether Upper Cervical Nerve Roots: A Potential Cause Of Postoperative C5 Palsy, Andrew S. Jack, Brooks R. Osburn, Zane A. Tymchak, Wyatt L. Ramey, Rod J. Oskouian, Robert A. Hart, Jens R. Chapman, Line G. Jacques, R. Shane Tubbs

Neurosurgery and Brain Repair Faculty Publications

Background: Nerve root tethering upon dorsal spinal cord (SC) migration has been proposed as a potential mechanism for postoperative C5 palsy (C5P). To our knowledge, this is the first study to investigate this relationship by anatomically comparing C5–C6 nerve root translation before and after root untethering by cutting the cervical foraminal ligaments (FL).

Objective: The aim of this study is to determine if C5 root untethering through FL cutting results in increased root translation.

Methods: Six cadaveric dissections were performed. Nerve roots were exposed via C4–C6 corpectomies and supraclavicular brachial plexus exposure. Pins were inserted into the C5–C6 roots and …


Mesenchymal Stem Cell Therapy Alleviates The Neuroinflammation Associated With Acquired Brain Injury, Brooke Bonsack, Sydney Corey, Alex Shear, Matt Heyck, Blaise Cozene, Nadia Sadanandan, Henry Zhang, Bella Gonzales-Portillo, Michael Sheyner, Cesar V. Borlongan Jan 2020

Mesenchymal Stem Cell Therapy Alleviates The Neuroinflammation Associated With Acquired Brain Injury, Brooke Bonsack, Sydney Corey, Alex Shear, Matt Heyck, Blaise Cozene, Nadia Sadanandan, Henry Zhang, Bella Gonzales-Portillo, Michael Sheyner, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Ischemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long-term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties, mesenchymal stem cell transplants have emerged as a promising approach to treating this facet of stroke and TBI pathology. In this review, we summarize the classification of cell death in ABI and discuss the prominent role of inflammation. We then …


Novel Titanium Cages For Minimally Invasive Lateral Lumbar Interbody Fusion: First Assessment Of Subsidence, Paul R. Krafft, Brooks Osburn, Andrew C. Vivas, Gautam Rao, Puya Alikhani Jan 2020

Novel Titanium Cages For Minimally Invasive Lateral Lumbar Interbody Fusion: First Assessment Of Subsidence, Paul R. Krafft, Brooks Osburn, Andrew C. Vivas, Gautam Rao, Puya Alikhani

Neurosurgery and Brain Repair Faculty Publications

Introduction: Implant subsidence is a potential complication of spinal interbody fusion and may negatively affect patients subjected to procedures relying on indirect decompression such as minimally invasive transpsoas lateral lumbar interbody fusion (LLIF). The porous architecture of a recently developed titanium intervertebral cage maximizes bone-to-implant contact and minimizes stress shielding in laboratory experiments; however, its subsidence rate in patients has not yet been evaluated. The goal of this current study was to evaluate implant subsidence in patients subjected to LLIF.

Methods: Our institutional review board-approved single-center experience included 29 patients who underwent 30 minimally invasive LLIF from July 2017 to …


Eyeballing Stroke: Blood Flow Alterations In The Eye And Visual Impairments Following Transient Middle Cerebral Artery Occlusion In Adult Rats, Jea-Young Lee, Vanessa Castelli, Brooke Bonsack, Julián García-Sánchez, Chase Kingsbury, Hung Nguyen, Naoki Tajiri, Cesar V. Borlongan Jan 2020

Eyeballing Stroke: Blood Flow Alterations In The Eye And Visual Impairments Following Transient Middle Cerebral Artery Occlusion In Adult Rats, Jea-Young Lee, Vanessa Castelli, Brooke Bonsack, Julián García-Sánchez, Chase Kingsbury, Hung Nguyen, Naoki Tajiri, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Middle cerebral artery occlusion in rodents remains a widely used model of ischemic stroke. Recently, we reported the occurrence of retinal ischemia in animals subjected to middle cerebral artery occlusion, owing in part to the circulatory juxtaposition of the ophthalmic artery to the middle cerebral artery. In this study, we examined the eye hemodynamics and visual deficits in middle cerebral artery occlusion-induced stroke rats. The brain and eye were evaluated by laser Doppler at baseline (prior to middle cerebral artery occlusion), during and after middle cerebral artery occlusion. Retinal function-relevant behavioral and histological outcomes were performed at 3 and 14 …


Spleen Participation In Partial Mhc Class Ii Construct Neuroprotection In Stroke, John Brown, Chase Kingsbury, Jea-Young Lee, Arthur A. Vandenbark, Roberto Meza-Romero, Halina Offner, Cesar V. Borlongan Jan 2020

Spleen Participation In Partial Mhc Class Ii Construct Neuroprotection In Stroke, John Brown, Chase Kingsbury, Jea-Young Lee, Arthur A. Vandenbark, Roberto Meza-Romero, Halina Offner, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Pathological progression of stroke in the peripheral and central nervous systems (PNS and CNS) is characterized by multiple converging signalling pathways that exacerbate neuroinflammation-mediated secondary cell death. This creates a need for a novel type of immunotherapy capable of simultaneously lowering the synergistic inflammatory responses in the PNS and CNS, specifically the spleen and brain. Previously, we demonstrated that partial major histocompatibility complex (MHC) class II constructs can be administered subcutaneously to promote histological and behavioural effects that alleviate common symptoms found in a murine model of transient stroke. This MHC class II manipulates T cell cytokine expression in both …


Translating Intracarotid Artery Transplantation Of Bone Marrow-Derived Ncs-01 Cells For Ischemic Stroke: Behavioral And Histological Readouts And Mechanistic Insights Into Stem Cell Therapy, Yuji Kaneko, Jea-Young Lee, Naoki Tajiri, Julian P. Tuazon, Trenton Lippert, Eleonora Russo, Seong-Jin Yu, Brooke Bonsack, Sydney Corey, Alexandreya B. Coats, Chase Kingsbury, Thomas N. Chase, Minako Koga, Cesar V. Borlongan Jan 2020

Translating Intracarotid Artery Transplantation Of Bone Marrow-Derived Ncs-01 Cells For Ischemic Stroke: Behavioral And Histological Readouts And Mechanistic Insights Into Stem Cell Therapy, Yuji Kaneko, Jea-Young Lee, Naoki Tajiri, Julian P. Tuazon, Trenton Lippert, Eleonora Russo, Seong-Jin Yu, Brooke Bonsack, Sydney Corey, Alexandreya B. Coats, Chase Kingsbury, Thomas N. Chase, Minako Koga, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

The present study used in vitro and in vivo stroke models to demonstrate the safety, efficacy, and mechanism of action of adult human bone marrow-derived NCS-01 cells. Coculture with NCS-01 cells protected primary rat cortical cells or human neural progenitor cells from oxygen glucose deprivation. Adult rats that were subjected to middle cerebral artery occlusion, transiently or permanently, and subsequently received intracarotid artery or intravenous transplants of NCS-01 cells displayed dose-dependent improvements in motor and neurological behaviors, and reductions in infarct area and peri-infarct cell loss, much better than intravenous administration. The optimal dose was 7.5 × 106 cells/mL when …


Traumatic Brain Injury, Julian E. Bailes, Cesar V. Borlongan Jan 2020

Traumatic Brain Injury, Julian E. Bailes, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.


2019 Overview, Cesario Borlongan, Frederic Dorandeu, Giuseppe Di Giovanni, Jian-Sheng Lin, Gang Hu, Johannes Boltze, Jie Wu, Xiaoming Hu, Yumin Luo Jan 2020

2019 Overview, Cesario Borlongan, Frederic Dorandeu, Giuseppe Di Giovanni, Jian-Sheng Lin, Gang Hu, Johannes Boltze, Jie Wu, Xiaoming Hu, Yumin Luo

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.


Advancing Stem Cell Therapy For Repair Of Damaged Lung Microvasculature In Amyotrophic Lateral Sclerosis, Svitlana Garbuzova-Davis, Robert Shell, Hilmi Mustafa, Surafuale Hailu, Alison E. Willing, Paul R. Sanberg, Cesar V. Borlongan Jan 2020

Advancing Stem Cell Therapy For Repair Of Damaged Lung Microvasculature In Amyotrophic Lateral Sclerosis, Svitlana Garbuzova-Davis, Robert Shell, Hilmi Mustafa, Surafuale Hailu, Alison E. Willing, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration in the brain and spinal cord. Progressive paralysis of the diaphragm and other respiratory muscles leading to respiratory dysfunction and failure is the most common cause of death in ALS patients. Respiratory impairment has also been shown in animal models of ALS. Vascular pathology is another recently recognized hallmark of ALS pathogenesis. Central nervous system (CNS) capillary damage is a shared disease element in ALS rodent models and ALS patients. Microvascular impairment outside of the CNS, such as in the lungs, may occur in ALS, triggering lung damage …


Potential Of Mesenchymal Stem Cells Alone, Or In Combination, To Treat Traumatic Brain Injury, Alison E. Willing, Mahasweta Das, Mark Howell, Shyam S. Mohapatra, Subhra Mohapatra Jan 2020

Potential Of Mesenchymal Stem Cells Alone, Or In Combination, To Treat Traumatic Brain Injury, Alison E. Willing, Mahasweta Das, Mark Howell, Shyam S. Mohapatra, Subhra Mohapatra

Neurosurgery and Brain Repair Faculty Publications

Traumatic brain injury (TBI) causes death and disability in the United States and around the world. The traumatic insult causes the mechanical injury of the brain and primary cellular death. While a comprehensive pathological mechanism of TBI is still lacking, the focus of the TBI research is concentrated on understanding the pathophysiology and developing suitable therapeutic approaches. Given the complexities in pathophysiology involving interconnected immunologic, inflammatory, and neurological cascades occurring after TBI, the therapies directed to a single mechanism fail in the clinical trials. This has led to the development of the paradigm of a combination therapeutic approach against TBI. …


Cell Therapy For Central Nervous System Disorders: Current Obstacles To Progress, Takao Yasuhara, Satoshi Kawauchi, Kyohei Kin, Jun Morimoto, Masahiro Kameda, Tatsuya Sasaki, Brooke Bonsack, Chase Kingsbury, Naoki Tajiri, Cesar V. Borlongan, Isao Date Jan 2020

Cell Therapy For Central Nervous System Disorders: Current Obstacles To Progress, Takao Yasuhara, Satoshi Kawauchi, Kyohei Kin, Jun Morimoto, Masahiro Kameda, Tatsuya Sasaki, Brooke Bonsack, Chase Kingsbury, Naoki Tajiri, Cesar V. Borlongan, Isao Date

Neurosurgery and Brain Repair Faculty Publications

Cell therapy for disorders of the central nervous system has progressed to a new level of clinical application. Various clinical studies are underway for Parkinson's disease, stroke, traumatic brain injury, and various other neurological diseases. Recent biotechnological developments in cell therapy have taken advantage of the technology of induced pluripotent stem (iPS) cells. The advent of iPS cells has provided a robust stem cell donor source for neurorestoration via transplantation. Additionally, iPS cells have served as a platform for the discovery of therapeutics drugs, allowing breakthroughs in our understanding of the pathology and treatment of neurological diseases. Despite these recent …


Pathophysiology Of Ganglioside Gm1 In Ischemic Stroke: Ganglioside Gm1: A Critical Review, Wenchao Zhang, Paul R. Krafft, Tianlong Wang, John H. Zhang, Li Li, Jiping Tang Jan 2019

Pathophysiology Of Ganglioside Gm1 In Ischemic Stroke: Ganglioside Gm1: A Critical Review, Wenchao Zhang, Paul R. Krafft, Tianlong Wang, John H. Zhang, Li Li, Jiping Tang

Neurosurgery and Brain Repair Faculty Publications

Ganglioside GM1 is a member of the ganglioside family which has been used in many countries and is thought of as a promising alternative treatment for preventing several neurological diseases, including cerebral ischemic injury. The therapeutic effects of GM1 have been proved both in neonates and in adults following ischemic brain damage; however, its clinical efficacy in patients with ischemic stroke is still uncertain. This review examines the recent knowledge of the neuroprotective properties of GM1 in ischemic stroke, collected in the past two decades. We conclude that GM1 may have potential for stroke treatment, although we need to be …


Microrna-133a And Myocardial Infarction, Yi Xiao, Jiling Zhao, Julian P. Tuazon, Cesar V. Borlongan, Guolong Yu Jan 2019

Microrna-133a And Myocardial Infarction, Yi Xiao, Jiling Zhao, Julian P. Tuazon, Cesar V. Borlongan, Guolong Yu

Neurosurgery and Brain Repair Faculty Publications

Myocardial infarction (MI) is the leading cause of morbidity and mortality in the world. The infarcted heart displays typical cell death cascades characterized by a loss of cells and fibrotic scarring in the myocardium. Cardiac hypertrophy and fibrosis largely contribute to ventricular wall thickening and stiffening, altogether defining an adverse cardiac remodeling that ultimately leads to impaired cardiac function and subsequent heart failure. Finding a strategy to promote therapeutic, instead of detrimental, cardiac remodeling may pose as a potent MI treatment. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. In particular, microRNA-133a (miR-133a) is …


Prophylactic Treatment Of Hyperbaric Oxygen Treatment Mitigates Inflammatory Response Via Mitochondria Transfer, Trenton Lippert, Cesar V. Borlongan Jan 2019

Prophylactic Treatment Of Hyperbaric Oxygen Treatment Mitigates Inflammatory Response Via Mitochondria Transfer, Trenton Lippert, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.


Gutting The Brain Of Inflammation: A Key Role Of Gut Microbiome In Human Umbilical Cord Blood Plasma Therapy In Parkinson's Disease Model, Jea-Young Lee, Julian P. Tuazon, Jared Ehrhart, Paul R. Sanberg, Cesar V. Borlongan Jan 2019

Gutting The Brain Of Inflammation: A Key Role Of Gut Microbiome In Human Umbilical Cord Blood Plasma Therapy In Parkinson's Disease Model, Jea-Young Lee, Julian P. Tuazon, Jared Ehrhart, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Current therapies for Parkinson's disease (PD), including L-3,4-dihydroxyphenylalanine (L-DOPA), and clinical trials investigating dopaminergic cell transplants, have generated mixed results with the eventual induction of dyskinetic side effects. Although human umbilical cord blood (hUCB) stem/progenitor cells present with no or minimal capacity of differentiation into mature dopaminergic neurons, their transplantation significantly attenuates parkinsonian symptoms likely via bystander effects, specifically stem cell graft-mediated secretion of growth factors, anti-inflammatory cytokines, or synaptic function altogether promoting brain repair. Recognizing this non-cell replacement mechanism, we examined here the effects of intravenously transplanted combination of hUCB-derived plasma into the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rat model of PD. …


Concise Review: Stem Cell Therapy For Stroke Patients: Are We There Yet?, Cesar V. Borlongan Jan 2019

Concise Review: Stem Cell Therapy For Stroke Patients: Are We There Yet?, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Four decades of preclinical research demonstrating survival, functional integration, and behavioral effects of transplanted stem cells in experimental stroke models have provided ample scientific basis for initiating limited clinical trials of stem cell therapy in stroke patients. Although safety of the grafted cells has been overwhelmingly documented, efficacy has not been forthcoming. Two recently concluded stroke clinical trials on mesenchymal stem cells (MSCs) highlight the importance of strict adherence to the basic science findings of optimal transplant regimen of cell dose, timing, and route of delivery in enhancing the functional outcomes of cell therapy. Echoing the Stem Cell Therapeutics as …


A Hallmark Clinical Study Of Cord Blood Therapy In Adults With Ischemic Stroke, Paul R. Sanberg, Jared Ehrhart Jan 2019

A Hallmark Clinical Study Of Cord Blood Therapy In Adults With Ischemic Stroke, Paul R. Sanberg, Jared Ehrhart

Neurosurgery and Brain Repair Faculty Publications

The therapeutic application of human umbilical cord blood cells has been an area of great interest for at least the last 25 years. Currently, cord blood cells are approved for reconstitution of the bone marrow following myeloablation in both young and old patients with myeloid malignancies and other blood cancers. Translational studies investigating alternative uses of cord blood have also shown that these cells not only stimulate neurogenesis in the aged brain but are also potentially therapeutic in the treatment of adult neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer’s disease, ischemic stroke, traumatic brain injury, and Parkinson’s disease. Recent advances …


Immunomodulation With Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis, Maple L. Shiao, Ce Yuan, Andrew T. Crane, Joseph P. Voth, Mario Juliano, Laura L. Hocum Stone, Zhenghong Nan, Ying Zhang, Nicole Kuzmin-Nichols, Paul R. Sanberg, Andrew W. Grande, Walter C. Low Jan 2019

Immunomodulation With Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis, Maple L. Shiao, Ce Yuan, Andrew T. Crane, Joseph P. Voth, Mario Juliano, Laura L. Hocum Stone, Zhenghong Nan, Ying Zhang, Nicole Kuzmin-Nichols, Paul R. Sanberg, Andrew W. Grande, Walter C. Low

Neurosurgery and Brain Repair Faculty Publications

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 …


Administration Of Rctrp9 Attenuates Neuronal Apoptosis Through Adipor1/Pi3k/Akt Signaling Pathway After Ich In Mice, Lianhua Zhao, John H. Zhang, Prativa Sherchan, Paul R. Krafft, Wei Zhao, Sa Wang, Shengpan Chen, Zaiyu Guo, Jiping Tang Jan 2019

Administration Of Rctrp9 Attenuates Neuronal Apoptosis Through Adipor1/Pi3k/Akt Signaling Pathway After Ich In Mice, Lianhua Zhao, John H. Zhang, Prativa Sherchan, Paul R. Krafft, Wei Zhao, Sa Wang, Shengpan Chen, Zaiyu Guo, Jiping Tang

Neurosurgery and Brain Repair Faculty Publications

Targeting neuronal apoptosis after intracerebral hemorrhage (ICH) may be an important therapeutic strategy for ICH patients. Emerging evidence indicates that C1q/TNF-Related Protein 9 (CTRP9), a newly discovered adiponectin receptor agonist, exerts neuroprotection in cerebrovascular disease. The aim of this study was to investigate the anti-apoptotic role of CTRP9 after experimental ICH and to explore the underlying molecular mechanisms. ICH was induced in mice via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administrated intranasally at 1 h after ICH. To elucidate the underlying mechanisms, adiponectin receptor1 small interfering ribonucleic acid (AdipoR1 siRNA) and selective PI3 K inhibitor LY294002 were …


Retrospective Case Series Of Traumatic Brain Injury And Post-Traumatic Stress Disorder Treated With Hyperbaric Oxygen Therapy, R. Douglas Shytle, David J. Eve, Soel-Hee Kim, Allan Spiegel, Paul R. Sanberg, Cesar V. Borlongan Jan 2019

Retrospective Case Series Of Traumatic Brain Injury And Post-Traumatic Stress Disorder Treated With Hyperbaric Oxygen Therapy, R. Douglas Shytle, David J. Eve, Soel-Hee Kim, Allan Spiegel, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Returning veterans are frequently diagnosed with traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Considering a recent case-controlled study of hyperbaric oxygen therapy (HBOT) reporting a reduction in suicidal ideation, we investigated retrospectively three veterans with chronic TBI/PTSD symptoms who were treated with multiple rounds of HBOT with neurophysiological testing performed before and after treatment. Improvements were detected on parameters within neurocognitive domains, including reductions in suicide-related symptoms. These findings independently confirm that HBOT may be effective in treating specific symptoms of TBI/PTSD that are not currently addressed with existing therapeutic approaches.


Therapeutic Cocktail Approach For Treatment Of Hyperhomocysteinemia In Alzheimer’S Disease, Michael Leon, Darrell Sawmiller, R. Douglas Shytle, Jun Tan Jan 2018

Therapeutic Cocktail Approach For Treatment Of Hyperhomocysteinemia In Alzheimer’S Disease, Michael Leon, Darrell Sawmiller, R. Douglas Shytle, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

In the United States, Alzheimer's disease (AD) is the most common cause of dementia, accompanied by substantial economic and emotional costs. During 2015, more than 15 million family members who provided care to AD patients had an estimated total cost of 221 billion dollars. Recent studies have shown that elevated total plasma levels of homocysteine (tHcy), a condition known as hyperhomocysteinemia (HHcy), is a risk factor for AD. HHcy is associated with cognitive decline, brain atrophy, and dementia; enhances the vulnerability of neurons to oxidative injury; and damages the blood–brain barrier. Many therapeutic supplements containing vitamin B12 and folate have …


Progress And Updates In Stroke Research: Introduction To The Special Issue On Stroke, Yu Luo, John H. Zhang, Paul R. Sanberg, Samantha M. Portis Jan 2018

Progress And Updates In Stroke Research: Introduction To The Special Issue On Stroke, Yu Luo, John H. Zhang, Paul R. Sanberg, Samantha M. Portis

Neurosurgery and Brain Repair Faculty Publications

As guest editors of this special issue, we are delighted to present 13 articles that discuss advances in stroke research including translational stroke research, stroke research milestones, and proposals for future directions. Stroke is a major cause of disability, and, according to the Centers for Disease Control and Prevention, is the fifth leading cause of death in the US alone. Possible factors contributing to stroke pathogenesis are elucidated and possible treatment modalities are explored in the following special issue of Cell Transplantation.


Wada Asymmetry In Patients With Drug-Resistant Mesial Temporal Lobe Epilepsy: Implications For Postoperative Neuropsychological Outcomes, Ryan W. Sever, Andrew C. Vivas, Fernando L. Vale, Mike R. Schoenberg Jan 2018

Wada Asymmetry In Patients With Drug-Resistant Mesial Temporal Lobe Epilepsy: Implications For Postoperative Neuropsychological Outcomes, Ryan W. Sever, Andrew C. Vivas, Fernando L. Vale, Mike R. Schoenberg

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.


Reduction Of Microhemorrhages In The Spinal Cord Of Symptomatic Als Mice After Intravenous Human Bone Marrow Stem Cell Transplantation Accompanies Repair Of The Blood-Spinal Cord Barrier, David J. Eve, George Steiner, Ajay Mahendrasah, Paul R. Sanberg, Crupa Kurien, Avery Thomson, Cesar V. Borlongan, Svitlana Garbuzova-Davis Jan 2018

Reduction Of Microhemorrhages In The Spinal Cord Of Symptomatic Als Mice After Intravenous Human Bone Marrow Stem Cell Transplantation Accompanies Repair Of The Blood-Spinal Cord Barrier, David J. Eve, George Steiner, Ajay Mahendrasah, Paul R. Sanberg, Crupa Kurien, Avery Thomson, Cesar V. Borlongan, Svitlana Garbuzova-Davis

Neurosurgery and Brain Repair Faculty Publications

Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34+ (hBM34+) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34+ cells (5 × 104, 5 × 105 or 1 × 106) or media were intravenously injected into symptomatic G93A SOD1 mice …


Human Cord Blood Serum-Derived App Α-Secretase Cleavage Activity Is Mediated By C1 Complement, Ahsan Habib, Darrell Sawmiller, Huayan Hou, Manasa Kanithi, Jun Tian, Jin Zeng, Dan Zi, Zhi-Xu He, Paul R. Sanberg, Jun Tan Jan 2018

Human Cord Blood Serum-Derived App Α-Secretase Cleavage Activity Is Mediated By C1 Complement, Ahsan Habib, Darrell Sawmiller, Huayan Hou, Manasa Kanithi, Jun Tian, Jin Zeng, Dan Zi, Zhi-Xu He, Paul R. Sanberg, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

Alzheimer’s Disease (AD) is the leading cause of dementia in the elderly. In healthy individuals, amyloid precursor protein (APP) is cleaved by α-secretase, generating soluble α-amyloid precursor protein (sAPPα), which contributes neuroprotective functions in the neuronal environment. In contrast, in the neurodegenerative environment of AD patients, amyloid-β-peptide (Aβ) of either 40 or 42 residues are generated by increased activity of β- and γ-secretase. These proteins amalgamate in specific regions of the brain, which disrupts neuronal functions and leads to cognitive impairment. Human umbilical cord blood cells (HUCBC) have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases, …


Human Umbilical Cord Blood Serum–Derived Α-Secretase: Functional Testing In Alzheimer’S Disease Mouse Models, Ahsan Habib, Huayan Hou, Takashi Mori, Jun Tian, Jin Zeng, Shengnuo Fan, Brian Giunta, Paul R. Sanberg, Darrell Sawmiller, Jun Tan Jan 2018

Human Umbilical Cord Blood Serum–Derived Α-Secretase: Functional Testing In Alzheimer’S Disease Mouse Models, Ahsan Habib, Huayan Hou, Takashi Mori, Jun Tian, Jin Zeng, Shengnuo Fan, Brian Giunta, Paul R. Sanberg, Darrell Sawmiller, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

Alzheimer’s disease (AD) is an age-related disorder that affects cognition. Our previous studies showed that the neuroprotective fragment of amyloid procurer protein (APP) metabolite, soluble APPα (sAPPα), interferes with β-site APP-cleaving enzyme 1 (BACE1, β-secretase) cleavage and reduces amyloid-β (Aβ) generation. In an attempt to identify approaches to restore sAPPα levels, we found that human cord blood serum (CBS) significantly promotes sAPPα production compared with adult blood serum (ABS) and aged blood serum (AgBS) in Chinese hamster ovary cells stably expressing wild-type human APP. Interestingly, CBS selectively mediated the α-secretase cleavage of human neuron-specific recombinant APP695 in a cell-free …


Plasma Derived From Human Umbilical Cord Blood: Potential Cell-Additive Or Cell-Substitute Therapeutic For Neurodegenerative Diseases, Jared Ehrhart, Paul R. Sanberg, Svitlana Garbuzova-Davis Jan 2018

Plasma Derived From Human Umbilical Cord Blood: Potential Cell-Additive Or Cell-Substitute Therapeutic For Neurodegenerative Diseases, Jared Ehrhart, Paul R. Sanberg, Svitlana Garbuzova-Davis

Neurosurgery and Brain Repair Faculty Publications

Limited efficacy of current therapeutic approaches for neurodegenerative disease has led to increased interest in alternative therapies. Cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may be a potential therapeutic. Benefits of CBP injection into rodent models of aging or ischaemic stroke have been demonstrated, though how benefits are elicited is still unclear. The present study evaluated various factors within the same samples of CBP and human adult blood plasma/sera (ABP/S). Also, autologous CBP effects vs. ABP/S or foetal bovine serum supplements on mononuclear cells from hUCB (MNC hUCB) in vitro were determined. Results showed significantly low …