Treatment Of Neurological Injuries Research Articles

Evaluation, Treatment, and Impact of Neurologic Injury in Adult Patients on Extracorporeal Membrane Oxygenation: a Review.

PurposeExtracorporeal membrane oxygen (ECMO) is increasingly used as an advanced form of life support for cardiac and respiratory failure. Unfortunately, in infrequent instances, circulatory and/or respiratory recovery is overshadowed by neurologic injury that can occur in patients who require ECMO. As such, knowledge of ECMO and its implications on diagnosis and treatment of neurologic injuries is indispensable for intensivists and neurospecialists.Recent findingsThe most common neurologic injuries include intracerebral hemorrhage, ischemic stroke, seizure, cerebral edema, intracranial hypertension, global cerebral hypoxia/anoxia, and brain death. These result from events prior to initiation of ECMO, failure of ECMO to provide adequate oxygen delivery, and/or complications that occur during ECMO. ECMO survivors also experience neurological and psychological sequelae similar to other survivors of critical illness.SummarySince many of the risk factors for neurologic injury cannot be easily mitigated, early diagnosis and intervention are crucial to limit morbidity and mortality from neurologic injury during ECMO.

Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications.

In addition to their cholesterol-lowering effects, statins are associated with pleiotropic effects including improvements in heart failure (HF), reduced blood pressure, prevention of the rupture of atherosclerotic plaques and improved angiogenesis. In addition to these cardiovascular benefits, statins have been implicated in the treatment of neurological injuries, cancer, sepsis, and cirrhosis. These cholesterol-independent beneficial effects of statins are predominantly mediated through signaling pathways leading to increased production and bioavailability of nitric oxide (NO). In this review, the mechanistic pathways and therapeutic effects of statin-mediated elevations of NO are described and discussed.

Neuroplasticity in Brain Injury: Maximizing Recovery

The ability to promote greater neuroplasticity through external influencers is an emerging field of study with potentially significant consequences on the treatment of neurologic injury. Several of these methods are reviewed in this paper. Through advances in neuroscience, a clearer understanding of the complexity of the brain’s interconnectedness and its ability to adapt to the environment is leading to neurorehabilitation treatments that augment the brain’s capacity towards neuroplastic change. An increased appreciation and recognition of neuroplasticity has led to novel approaches to promote neurorecovery that increase stimulation and the release of neutrophic factors. Some of these interventions include the use of pharmacologic agents, noninvasive stimulation, mirror therapy, aerobic and task-specific exercise, and the maximization of sleep. Future research will continue to build upon this foundation by continuing to pair therapeutic interventions with rehabilitation to enhance the brain’s natural healing power and improve functional outcomes.

Neuroprotective effect of ethanol in acute carbon monoxide intoxication: A retrospective study.

In acute carbon monoxide (CO) intoxication, treatment of neurologic injury and prevention of neurological sequelae are primary concerns. Ethanol is the one of the frequent substances which is co-ingested in intentional CO poisoning. Neuroprotective effect of ethanol was highlighted and demonstrated in isolated brain injury recently. We assessed the neuroprotective effect of ethanol in acute CO intoxication using magnetic resonance imaging (MRI).We retrospectively reviewed medical records for patients who visited an emergency medical center of a university-affiliated hospital during a period of 73 months, from March 2009 to April 2015. Enrolled patients were divided into 2 groups, patients with or without abnormal brain lesion in brain MRI. Multivariate logistic regression analysis was performed to assess the factors associated with brain injury in MRI.A total of 109 patients with acute CO intoxication were evaluated of which 66 (60.55%) tested positive in brain MRI. MRI lesion-positive patients were more likely to have electrocardiogram change, elevation of serum troponin I and s100 protein level and lower serum ethanol level. Serum ethanol positivity was an independent factor for prevalence of brain injury in MRI in acute CO poisoning.This study revealed that ethanol which is co-ingested in acute CO intoxication may work the neuroprotective effect and could consequence more favorable neurological outcome in acute CO intoxication.

Treatment of neurological injury with thymosin β4.

Neurorestorative therapy targets multiple types of parenchymal cells in the intact tissue of injured brain tissue to increase neurogenesis, angiogenesis, oligodendrogenesis, and axonal remodeling during recovery from neurological injury. In our laboratory, we tested thymosin β4 (Tβ4) as a neurorestorative agent to treat models of neurological injury. This review discusses our results demonstrating that Tβ4 improves neurological functional outcome in a rat model of embolic stroke, a mouse model of multiple sclerosis, and a rat model of traumatic brain injury. Tβ4 is a pleiotropic peptide exhibiting many actions in several different types of tissues. One mechanism associated with improvement of neurological improvement from Tβ4 treatment is oligodendrogenesis involving the differentiation of oligodendrocyte progenitor cells to mature myelin-secreting oligodendrocytes. Moreover, our preclinical data provide a basis for movement of Tβ4 into clinical trials for treatment of these devastating neurological diseases and injuries.

New Approaches to Neuroprotection in Infant Heart Surgery

Advances in surgical techniques and perioperative management have led to dramatic improvements in outcomes for children with complex congenital heart disease (CHD). As the number of survivors continues to grow, clinicians are becoming increasingly aware that adverse neurodevelopmental outcomes after surgical repair of CHD represent a significant cause of morbidity, with widespread neuropsychologic deficits in as many as 50% of these children by the time they reach school age. Modifications of intraoperative management have yet to measurably impact long-term neurologic outcomes. However, exciting advances in our understanding of the underlying mechanisms of cellular injury and of the events that mediate endogenous cellular protection have provided a variety of new potential targets for the assessment, prevention, and treatment of neurologic injury in patients with CHD. In this review, we will discuss the unique challenges to developing neuroprotective strategies in children with CHD and consider how multisystem approaches to neuroprotection, such as ischemic preconditioning, will be the focus of ongoing efforts to develop new diagnostic tools and therapies. Although significant challenges remain, tremendous opportunity exists for the development of diagnostic and therapeutic interventions that can serve to limit neurologic injury and ultimately improve outcomes for infants and children with CHD.

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Insights into neural stem cell biology from flies

Drosophila neuroblasts are similar to mammalian neural stem cells in their ability to self-renew and to produce many different types of neurons and glial cells. In the past two decades, great advances have been made in understanding the molecular mechanisms underlying embryonic neuroblast formation, the establishment of cell polarity and the temporal regulation of cell fate. It is now a challenge to connect, at the molecular level, the different cell biological events underlying the transition from neural stem cell maintenance to differentiation. Progress has also been made in understanding the later stages of development, when neuroblasts become mitotically inactive, or quiescent, and are then reactivated postembryonically to generate the neurons that make up the adult nervous system. The ability to manipulate the steps leading from quiescence to proliferation and from proliferation to differentiation will have a major impact on the treatment of neurological injury and neurodegenerative disease.

Neuroplasticity and Brain Imaging Research: Implications for Rehabilitation

Levin HS. Neuroplasticity and brain imaging research: implications for rehabilitation. Advanced brain imaging technologies have been used recently to investigate neuroplasticity in relation to recovery and treatment of neurologic injury and disease. The contributors to this supplement present data and synthesize the extant literature on the use of functional magnetic resonance imaging, magnetic resonance spectroscopy, optical imaging, transcranial magnetic stimulation, and transcranial direct current stimulation to study remodeling of cortical representation of motor and cognitive abilities after stroke and other etiologies of neurologic impairment. In general, the collective findings of these studies support use-dependent neuroplasticity as a mechanism of recovery and response to training. Brain imaging findings support the role of training effects on increased activation of brain regions ipsilateral to unilateral vascular lesions in facilitating recovery from stroke. The articles in this supplement also report the potential therapeutic application of stimulation techniques to enhance reorganization of function.

Therapeutic potential of stem cells in perinatal medicine

Increasing evidence suggests that stem cells have tremendous potential to facilitate repair of damaged tissue and to exert protective influences that limit the extent of damage. Their inherent capacity to respond to signals generated by damaged tissue, migrate to these regions and either replace dead tissue or deliver protection by secretion of specific growth hormones and protective factors, suggests that they might have unrivalled therapeutic potential in perinatal medicine. A further potential of stem cells is their use in gene repair strategies for genetic disorders; an application which is exceedingly interesting from a perinatal perspective. Because of the relatively small size of infants and their capacity for future growth, stem cell therapy could be more successful in newborns than in older children or adults. In practical terms, the placenta, with its large reservoir of fetal blood, offers the ideal source of autologous stem cells. This affords the opportunity for stem cells to be collected and used, either directly ex vivo or after in vitro modulation, both for disorders in the neonatal period and for those arising later in life. The organs most affected from tissue damage in the neonatal period are the brain and the lung. So far, the most promising application of stem cells might be in the treatment of neurological injury. In this review we discuss recent research findings with adult stem cell therapy and their potential use in perinatal medicine. Furthermore, specific animal models suitable to explore the patho-physiological mechanisms of stem cell transplantation after neurological injury will be discussed. This review gives an overview of basic science findings and their possible role for clinical application with regards to the therapeutic potential of stem cells in perinatal medicine. Medline was searched for journal selection in peer-reviewed journals with high impact scores, which were relevant to this topic. All articles were in English and the search was not limited by publication year. However, the oldest publication was dated 1988 (reference 1).

Preliminary Report of the Effects of Complement Suppression With Pexelizumab on Neurocognitive Decline After Coronary Artery Bypass Graft Surgery

Pharmacological modulation of complement activation recently has been postulated as a therapeutic target in the treatment of neurological injury. We hypothesized that pexelizumab, a humanized scFv monoclonal antibody directed against the C5 complement component, would limit deficits in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. The Phase II Pexelizumab study was a 914-patient, double-blind, placebo-controlled, 65-center study of patients undergoing coronary artery bypass graft surgery. Patients were randomized to pexelizumab bolus, bolus plus infusion, or placebo. Neurological and neurocognitive functions were assessed as secondary endpoints at baseline and on postoperative days (POD) 4 and 30. Cognitive deficits were assessed with multivariable tests accounting for baseline cognition, age, diabetes, years of education, sex, elevated creatinine, history of myocardial infarction, neurological disorder or congestive heart failure, and cardiopulmonary bypass time. Pexelizumab had no statistically significant effect on the primary composite endpoint or on overall cognition. When domain specific effects were examined, a decline of at least 10% in the visuo-spatial domain was observed on POD 4 in 56% of patients receiving placebo compared with 40% receiving pexelizumab by bolus and infusion (P=0.003). Similarly, on POD 30, a 10% decline was present in 21% of patients in the placebo group versus only 12% of the drug bolus plus infusion group (P=0.016). No differences were seen between treatment groups in any of the other domains. Pexelizumab administration for 24 hours perioperatively had no effect on global measures of cognition but may reduce dysfunction in the visuo-spatial domain.

The Effects of Dizocilpine Maleate (MK-801), an Antagonist of the N-Methyl-D-Aspartate Receptor, on Neurologic Recovery and Histopathology following Complete Cerebral Ischemia in Primates

The present study was designed to determine if the noncompetitive excitatory amino acid antagonist, dizocilpine maleate, when administered after a 17 min period of complete cerebral ischemia in primates, would improve postischemic neurologic function and hippocampal histopathologic outcome when compared to placebo-treated animals. Ten pigtail monkeys were anesthetized and subjected to complete cerebral ischemia using an established neck tourniquet model. Five minutes postischemia, five monkeys received dizocilpine 300 micrograms/kg i.v. over 5 min, followed by an infusion of 150 micrograms/kg/h for 10 h. This produced plasma levels of the drug in excess of 30 ng/ml for the duration of the infusion. An additional five monkeys were treated with an identical volume of saline placebo. All monkeys received intensive care for the initial 24 to 48 h postischemia. At 96 h postischemia, there was no significant difference in neurologic function between the two groups (p = 0.53, with the placebo group having the numerically better outcome). There also was no significant difference between hippocampal histopathology scores between dizocilpine and placebo-treated monkeys. The authors conclude that dizocilpine is not an efficacious therapy in the treatment of neurologic injury that occurs following complete cerebral ischemia in this primate model.