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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.

Farhat H.I.,University of Miami | Farhat H.I.,Lois Pope Center | Hood B.,University of Miami | Bullock M.R.,University of Miami
Journal of Emergency Medicine | Year: 2012

Background: Patients with tangential gunshot wounds (TGSWs) commonly present with a good Glasgow Coma Scale score and without a history of loss of consciousness. Typically, the bullet does not breach the skull, however, there is a considerable force directed into the brain, and these patients are best treated as sustaining a moderate-to-severe blunt head injury. These patients require observation and repeat imaging. Physicians should be aware of this entity as these patients can deteriorate in a delayed fashion. Objectives: The authors present a case of a TGSW to the head in a neurologically intact patient. The initial post-injury computed tomography (CT) scan showed a very small subdural hematoma (SDH) with no overlying fracture of the skull. A delayed CT scan performed 4 h after arrival to the Emergency Department and 6 h after injury demonstrated an increase in size of the SDH, new traumatic subarachnoid hemorrhage, and bilateral cerebral contusions. Clinically, the patient showed worsening of her neurological examination. She underwent aggressive non-surgical treatment for increased intracranial pressure with almost complete recovery. Conclusion: Although patients with TGSWs are typically in good condition upon presentation, these injuries are not always trivial, and these patients should have, at minimum, a non-contrast brain CT scan to evaluate underlying damage to the brain and skull. In addition, a delayed CT scan and close observation on a neurosurgical service are indicated.

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.

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