Lois Pope Center

Miami, FL, United States

Lois Pope Center

Miami, FL, United States
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PubMed | Lois Pope Center, Beth Israel Deaconess Medical Center and New York Medical College
Type: Journal Article | Journal: Journal of neurotrauma | Year: 2016

While various approaches have been proposed in clinical trials aimed at improving motor function after spinal cord injury in humans, there is still limited information regarding the scope, methodological quality, and evidence associated with single-intervention and multi-intervention approaches. A systematic review performed using the PubMed search engine and the key words spinal cord injury motor recovery identified 1973 records, of which 39 were selected (18 from the search records and 21 from reference list inspection). Study phase ( clinicaltrials.org criteria) and methodological quality (Cochrane criteria) were assessed. Studies included proposed a broad range of single-intervention (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) and multi-intervention approaches (that combined more than one strategy). The highest evidence level was for Phase III studies supporting the role of multi-intervention approaches that contained a rehabilitation component. Quality appraisal revealed that the percentage of selected studies classified with high risk of bias by Cochrane criteria was as follows: random sequence generation = 64%; allocation concealment = 77%; blinding of participants and personnel = 69%; blinding of outcome assessment = 64%; attrition = 44%; selective reporting = 44%. The current literature contains a high proportion of studies with a limited ability to measure efficacy in a valid manner because of low methodological strength in all items of the Cochrane risk of bias assessment. Recommendations to decrease bias are discussed and include increased methodological rigor in the study design and recruitment of study participants, and the use of electrophysiological and imaging measures that can assess functional integrity of the spinal cord (and may be sufficiently sensitive to detect changes that occur in response to therapeutic interventions).


Gomes-Osman J.,Beth Israel Deaconess Medical Center | Cortes M.,Cornell College | Guest J.,Lois Pope Center | Pascual-Leone A.,Beth Israel Deaconess Medical Center
Journal of Neurotrauma | Year: 2016

While various approaches have been proposed in clinical trials aimed at improving motor function after spinal cord injury in humans, there is still limited information regarding the scope, methodological quality, and evidence associated with single-intervention and multi-intervention approaches. A systematic review performed using the PubMed search engine and the key words "spinal cord injury motor recovery" identified 1973 records, of which 39 were selected (18 from the search records and 21 from reference list inspection). Study phase (clinicaltrials.org criteria) and methodological quality (Cochrane criteria) were assessed. Studies included proposed a broad range of single-intervention (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) and multi-intervention approaches (that combined more than one strategy). The highest evidence level was for Phase III studies supporting the role of multi-intervention approaches that contained a rehabilitation component. Quality appraisal revealed that the percentage of selected studies classified with high risk of bias by Cochrane criteria was as follows: random sequence generation = 64%; allocation concealment = 77%; blinding of participants and personnel = 69%; blinding of outcome assessment = 64%; attrition = 44%; selective reporting = 44%. The current literature contains a high proportion of studies with a limited ability to measure efficacy in a valid manner because of low methodological strength in all items of the Cochrane risk of bias assessment. Recommendations to decrease bias are discussed and include increased methodological rigor in the study design and recruitment of study participants, and the use of electrophysiological and imaging measures that can assess functional integrity of the spinal cord (and may be sufficiently sensitive to detect changes that occur in response to therapeutic interventions). © Mary Ann Liebert, Inc. 2016.


De Rivero Vaccari J.P.,Lois Pope Center | Dietrich W.D.,Lois Pope Center | Keane R.W.,Lois Pope Center | Keane R.W.,University of Miami
Translational Research | Year: 2016

Innate immunity is part of the early response of the body to deal with tissue damage and infections. Because of the early nature of the innate immune inflammatory response, this inflammatory reaction represents an attractive option as a therapeutic target. The inflammasome is a component of the innate immune response involved in the activation of caspase 1 and the processing of pro-interleukin 1β. In this article, we discuss the therapeutic potential of the inflammasome after central nervous system (CNS) injury and stroke, as well as the basic knowledge we have gained so far regarding inflammasome activation in the CNS. In addition, we discuss some of the therapies available or under investigation for the treatment of brain injury, spinal cord injury, and stroke. © 2016 Elsevier Inc.


Sick J.,University of Miami | Bray E.,University of Miami | Bregy A.,University of Miami | Bregy A.,Lois Pope Center | And 5 more authors.
Source Code for Biology and Medicine | Year: 2013

Background: Identifying and quantifying pathological changes in brain electrical activity is important for investigations of brain injury and neurological disease. An example is the development of epilepsy, a secondary consequence of traumatic brain injury. While certain epileptiform events can be identified visually from electroencephalographic (EEG) or electrocorticographic (ECoG) records, quantification of these pathological events has proved to be more difficult. In this study we developed MATLAB-based software that would assist detection of pathological brain electrical activity following traumatic brain injury (TBI) and present our MATLAB code used for the analysis of the ECoG.Methods: Software was developed using MATLAB(™) and features of the open access EEGLAB. EEGgui is a graphical user interface in the MATLAB programming platform that allows scientists who are not proficient in computer programming to perform a number of elaborate analyses on ECoG signals. The different analyses include Power Spectral Density (PSD), Short Time Fourier analysis and Spectral Entropy (SE). ECoG records used for demonstration of this software were derived from rats that had undergone traumatic brain injury one year earlier.Results: The software provided in this report provides a graphical user interface for displaying ECoG activity and calculating normalized power density using fast fourier transform of the major brain wave frequencies (Delta, Theta, Alpha, Beta1, Beta2 and Gamma). The software further detects events in which power density for these frequency bands exceeds normal ECoG by more than 4 standard deviations. We found that epileptic events could be identified and distinguished from a variety of ECoG phenomena associated with normal changes in behavior. We further found that analysis of spectral entropy was less effective in distinguishing epileptic from normal changes in ECoG activity.Conclusion: The software presented here was a successful modification of EEGLAB in the Matlab environment that allows detection of epileptiform ECoG signals in animals after TBI. The code allows import of large EEG or ECoG data records as standard text files and uses fast fourier transform as a basis for detection of abnormal events. The software can also be used to monitor injury-induced changes in spectral entropy if required. We hope that the software will be useful for other investigators in the field of traumatic brain injury and will stimulate future advances of quantitative analysis of brain electrical activity after neurological injury or disease. © 2013 Sick et al.; licensee BioMed Central Ltd.


Chan W.-M.,University of Miami | Mohammed Y.,University of Miami | Lee I.,University of Miami | Pearse D.D.,University of Miami | Pearse D.D.,Lois Pope Center
Translational Stroke Research | Year: 2013

Spinal cord injury (SCI) is a debilitating condition that affects thousands of new individuals each year, the majority of which are males. Males with SCI tend to be injured at an earlier age, mostly during sports or motor vehicle accidents, whereas females tend be injured later in life, particularly in the age group 65 and older. In both experimental and clinical studies, the question as to whether gender affects outcome has been addressed in a variety of patient groups and animal models. Results from experimental paradigms have suggested that a gender bias in outcome exists that favors females and appears to involve the advantageous or disadvantageous effects of the gonadal sex hormones estrogen and progesterone or testosterone, respectively. However, other studies have shown an absence of gender differences in outcome in specific SCI models and work has also questioned the involvement of female sex hormones in the observed outcome improvements in females. Similar controversy exists clinically, in studies that have examined gender disparities in outcome after SCI. The current review examines the experimental and clinical evidence for a gender bias in outcome following SCI and discusses issues that have made it difficult to conclusively answer this question. © 2013 Springer Science+Business Media New York.


De Rivero Vaccari J.P.,Lois Pope Center | Dietrich W.D.,Lois Pope Center | Keane R.W.,University of Miami
Journal of Cerebral Blood Flow and Metabolism | Year: 2014

The inflammasome is an intracellular multiprotein complex involved in the activation of caspase-1 and the processing of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18. The inflammasome in the central nervous system (CNS) is involved in the generation of an innate immune inflammatory response through IL-1 cytokine release and in cell death through the process of pyroptosis. In this review, we consider the different types of inflammasomes (NLRP1, NLRP2, NLRP3, and AIM2) that have been described in CNS cells, namely neurons, astrocytes, and microglia. Importantly, we focus on the role of the inflammasome after brain and spinal cord injury and cover the potential activators of the inflammasome after CNS injury such as adenosine triphosphate and DNA, and the therapeutic potential of targeting the inflammasome to improve outcomes after CNS trauma. © 2014 ISCBFM All rights reserved.


Guest J.,Lois Pope Center | Santamaria A.J.,Lois Pope Center | Benavides F.D.,Lois Pope Center
Current Opinion in Organ Transplantation | Year: 2013

Purpose of review: To describe the current status of testing Schwann cell transplantation as a therapy for human spinal cord injury (SCI). Recent findings: Transplanted Schwann cells have reparative effects in the damaged spinal cord. A few clinical studies have reported that Schwann cell transplantation appears safe. Compared with allogeneic cell transplants, autologous cells do not require immune suppression, but the workload of cell manufacturing is greater. Preclinical Schwann cell transplant studies conducted at the University of Miami in 2009-2012 supported an investigational new drug approved by the Food and Drug Administration. A Phase 1 safety study has been initiated. Summary: Spinal cord repair after severe SCI requires that axonal regeneration and myelination occur in a context of reduced inhibition, enhanced plasticity, and new circuit formation. Evolving clinical experience with Schwann cell transplantation may provide a basis upon which additionally combined therapeutics can be tested to increase the extent of repair after SCI. Safety is the primary consideration when ex-vivo manipulated cells are introduced into the damaged nervous system. Preclinical studies across several species have not indicated safety concerns regarding Schwann cells. Initial clinical reports from studies in Iran and China are suggestive of clinical safety, although more rigorous characterization of the implanted cells is needed. Copyright © 2013, Lippincott Williams & Wilkins.


PubMed | Lois Pope Center
Type: Journal Article | Journal: Current opinion in organ transplantation | Year: 2013

To describe the current status of testing Schwann cell transplantation as a therapy for human spinal cord injury (SCI).Transplanted Schwann cells have reparative effects in the damaged spinal cord. A few clinical studies have reported that Schwann cell transplantation appears safe. Compared with allogeneic cell transplants, autologous cells do not require immune suppression, but the workload of cell manufacturing is greater. Preclinical Schwann cell transplant studies conducted at the University of Miami in 2009-2012 supported an investigational new drug approved by the Food and Drug Administration. A Phase 1 safety study has been initiated.Spinal cord repair after severe SCI requires that axonal regeneration and myelination occur in a context of reduced inhibition, enhanced plasticity, and new circuit formation. Evolving clinical experience with Schwann cell transplantation may provide a basis upon which additionally combined therapeutics can be tested to increase the extent of repair after SCI. Safety is the primary consideration when ex-vivo manipulated cells are introduced into the damaged nervous system. Preclinical studies across several species have not indicated safety concerns regarding Schwann cells. Initial clinical reports from studies in Iran and China are suggestive of clinical safety, although more rigorous characterization of the implanted cells is needed.

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