scholarly journals Perinatal Hypoxic-Ischemic Damage: Review of the Current Treatment Possibilities

2021 ◽  
pp. S379-S401
Author(s):  
A FRAJEWICKI ◽  
Z LAŠTŮVKA ◽  
V BORBÉLYOVÁ ◽  
S KHAN ◽  
K JANDOVÁ ◽  
...  
Keyword(s):  
Muscle Tone ◽  
Research Effort ◽  
Treatment Strategies ◽  
Perinatal Period ◽  
Current Treatment ◽  
Hypoxic Ischemic Encephalopathy ◽  
Treatment Modalities ◽  
Motor Disabilities ◽  
Promising Treatment ◽  
Ischemic Encephalopathy

Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy. Despite an extensive research effort regarding various treatment strategies, therapeutic hypothermia with intensive care unit supportive treatment remains the only approved method for neonates who have suffered from moderate to severe hypoxic-ischemic encephalopathy. However, these protocols are only partially effective given that many infants still suffer from severe brain damage. Thus, further research to systematically test promising neuroprotective treatments in combination with hypothermia is essential. In this review, we discussed the pathophysiology of hypoxic-ischemic encephalopathy and delved into different promising treatment modalities, such as melatonin and erythropoietin. However, preclinical studies and clinical trials are still needed to further elucidate the mechanisms of action of these modalities.

scholarly journals Early Neurological Assessment in Infants with Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia

2019 ◽  
Vol 8 (8) ◽  
pp. 1247
Author(s):  
Domenico M. Romeo ◽  
Sarah Bompard ◽  
Francesca Serrao ◽  
Giuseppina Leo ◽  
Gianpaolo Cicala ◽  
...  
Keyword(s):  
Neurological Examination ◽  
Motor Impairment ◽  
Hypoxic Ischemic Encephalopathy ◽  
Neurological Assessment ◽  
Neurodevelopmental Outcomes ◽  
Good Tool ◽  
Motor Disabilities ◽  
High Risk Infants ◽  
Ischemic Encephalopathy

Early neurological assessment in infants with hypoxic ischemic encephalopathy (HIE) treated with hypothermia has not been systematically explored. The aims of the present study were to assess whether the Hammersmith Infant Neurological Examination (HINE) is a good tool to predict later neurodevelopmental outcomes at 2 year from birth in this population of infants. A total of 41 term born infants with HIE treated with hypothermia performed the HINE at 12 months and a neurodevelopmental assessment at 24 months. All the infants who had a global HINE score between 67 and 78 were able to walk independently at 2 years and reported a normal developmental quotient; language disorders were observed in a limited number of infants. HINE scores <67 were always associated with motor impairment. In conclusion, the HINE confirms its role as one of the early neurological examination tools for the diagnosis of high risk infants, even in infants with HIE treated with hypothermia. These results can be useful for clinicians involved in the follow up of these infants for early identification of motor disabilities and in planning appropriate intervention.

Induced Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Pathophysiology, Current Treatment, and Nursing Considerations

2011 ◽  
Vol 30 (1) ◽  
pp. 29-36 ◽  
Author(s):  
DeLinda Jo Cooper
Keyword(s):  
Brain Injury ◽  
Healing Process ◽  
Current Treatment ◽  
Therapeutic Interventions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Second Phase ◽  
Induced Hypothermia ◽  
Compensatory Mechanism ◽  
Neuroprotective Strategy ◽  
Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE) can lead to devastating neurodevelopmental consequences such as cerebral palsy, seizure disorders, and significant developmental delays. HIE in the newborn is often the result of a hypoxic event, such as uterine rupture, placental abruption, or cord prolapse. Biphasic brain injury occurs in HIE. The first phase involves activation of the sympathetic nervous system as a compensatory mechanism. The second phase, known as reperfusion brain injury, occurs hours later. Induced hypothermia, a neuroprotective strategy for treating HIE, targets the second phase to prevent reperfusion injury. NICU nurses are in a unique position to detect patient instability and to maintain the therapeutic interventions that contribute to the healing process. This article highlights the significant role nurses play in the management of infants diagnosed with HIE who are treated with induced hypothermia.

scholarly journals Preconditioning and Postinsult Therapies for Perinatal Hypoxic–Ischemic Injury at Term

2010 ◽  
Vol 113 (1) ◽  
pp. 233-249 ◽  
Author(s):  
Robert D. Sanders ◽  
Helen J. Manning ◽  
Nicola J. Robertson ◽  
Daqing Ma ◽  
A. David Edwards ◽  
...  
Keyword(s):  
Perinatal Period ◽  
Rapid Identification ◽  
Postnatal Period ◽  
Hypoxic Ischemic Encephalopathy ◽  
Current Status ◽  
Neuroprotective Agents ◽  
Period 2 ◽  
Neuroprotective Strategies ◽  
The Brain ◽  
Ischemic Encephalopathy

Perinatal hypoxic-ischemic encephalopathy can be a devastating complication of childbirth. Herein, the authors review the pathophysiology of hypoxic-ischemic encephalopathy and the current status of neuroprotective strategies to ameliorate the injury centering on four themes: (1) monitoring in the perinatal period, (2) rapid identification of affected neonates to allow timely institution of therapy, (3) preconditioning therapy (a therapeutic that reduces the brain vulnerability) before hypoxic-ischemic encephalopathy, and (4) prompt institution of postinsult therapies to ameliorate the evolving injury. Recent clinical trials have demonstrated the significant benefit for hypothermic therapy in the postnatal period; furthermore, there is accumulating preclinical evidence that adjunctive therapies can enhance hypothermic neuroprotection. Advances in the understanding of preconditioning may lead to the administration of neuroprotective agents earlier during childbirth. Although most of these neuroprotective strategies have not yet entered clinical practice, there is a significant hope that further developments will enhance hypothermic neuroprotection.

scholarly journals GCT-23. MULTI-INSTITUTIONAL ANALYSIS OF TREATMENT MODALITIES IN BASAL GANGLIA AND THALAMIC GERMINOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii332-iii332
Author(s):  
Richard T Graham ◽  
Mohammad H Abu-Arja ◽  
Joseph Stanek ◽  
Ute Bartels ◽  
Andrea Cappellano ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Institutional Analysis ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Event Free Survival ◽  
Free Survival ◽  
Combine Chemotherapy ◽  
Imaging Characteristics ◽  
Significant Difference

Abstract BACKGROUND Central nervous system (CNS) germinomas are radiotherapy (RT)-sensitive tumors with excellent survival. Current treatment strategies combine chemotherapy with RT to reduce the field and dose of RT. There is no standard treatment for germinomas originating in the basal ganglia/thalami (BGTG) given their rarity and poorly-defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have been previously utilized; however, the optimal strategy remains unclear. METHODS Retrospective multi-institutional analysis was conducted across 18 institutions in four countries. RESULTS For 46 cases with non-metastatic BGTG, the event-free survival (EFS) was 86.9% at both 5 and 10 years, while overall survival (OS) was 100%, and 95.7% respectively at 5 and 10 years. Median RT dose and range for the various treatment volumes were as follows: CSI (n=10): 2340 cGy (1980–3060 cGy), WBI (n=8): 2340 (1800–3000 cGy), WVI (n=14): 2340 cGy (1800–2550 cGy), focal (n=9): 3600 cGy (3060–5400 cGy). There was no statistically significant difference in the EFS based on RT modality (p=0.57), but EFS for subjects with CSI and WBI were both 100%. The three subjects who received chemotherapy alone had significantly lower EFS than those who received chemotherapy and RT (p=0.001), but were salvageable with RT. CONCLUSION In the largest study to date for BGTG, there were no significant differences in outcomes between patients who received CSI, WBI, WVI or focal RT. This group of patients should be included in future prospective clinical trials, and a more limited RT field may be considered.

CD70 as a critical mediator of tumor progression and immunosuppression in gliomas.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 18-18
Author(s):  
Changlin Yang ◽  
Haitao Ge ◽  
Linchun Jin ◽  
Qiong J. Wang ◽  
James C. Yang ◽  
...  
Keyword(s):  
Tumor Progression ◽  
T Regulatory Cells ◽  
Malignant Gliomas ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Specific Cell ◽  
Low Grade ◽  
Chemokine Production ◽  
Poor Survival Outcome

18 Background: For malignant gliomas, current treatment modalities are rarely curative, necessitating development of novel therapies. Cancer immunotherapy has represented one of the most promising new treatment strategies for patients with gliomas based on the evidence that patients with brain tumors are able to mount immune responses against the autologous tumors. However, very few tumor specific targets have been discovered in this malignancy. Thus, identifying clinical useful targets for immunotherapeutic approaches is desperately needed. Methods: CD70 expression was tested from primary GBM and low grade gliomas patient tissues. CD70 gene expression and clinical outcomes were culled from TCGA datasets. CD70 inducing CD8 T cells death was performed by flowcytometry. Results: We demonstrate that CD70, a member of the TNF ligand family, was constitutively overexpressed by primary IDH-wild-type LGG and GBMs with mesenchymal gene signatures. Elevated CD70 expression was also found in recurrent tumors and correlated with tumor progression and poor survival outcome in LGGs and GBMs. CD70 was shown to be directly involved in tumor-chemokine production and associated with sustained T regulatory cells in tumor. Importantly, CD70 played a role inducing CD8+T- specific cell death via engagement of the EREG-EGFR axis in glioma. Conclusions: CD70 is a multi-pronged modulator of immunosuppression in gliomas and enhances tumor progression.

The Use of Whole Body Cooling in the Treatment of Hypoxic-Ischemic Encephalopathy

2017 ◽  
Vol 36 (5) ◽  
pp. 273-279 ◽  
Author(s):  
Tiffany Harriman ◽  
Wanda T. Bradshaw ◽  
Stephanie M. Blake
Keyword(s):  
English Language ◽  
Current Treatment ◽  
Hypoxic Ischemic Encephalopathy ◽  
Whole Body ◽  
Neurodevelopmental Outcomes ◽  
Near Term ◽  
Body Cooling ◽  
Whole Body Cooling ◽  
Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in neonates. Hypoxic-ischemic encephalopathy occurs as a result of a perinatal hypoxic-ischemic event just prior to or during delivery. Therapeutic hypothermia using whole body cooling is the current treatment of choice to reduce brain injury and improve long-term neurodevelopmental outcomes for neonates with HIE. All English language articles published since 2005 in PubMed and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were analyzed for existing evidence-based methods for whole body cooling. Whole body cooling is effective in the treatment of HIE in term and near-term neonates. Further research is needed to investigate the use of adjunctive therapies in conjunction with whole body cooling for improved neuroprotection.

scholarly journals Immune Dysfunction and Multiple Treatment Modalities for the SARS-CoV-2 Pandemic: Races of Uncontrolled Running Sweat?

Biology ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 243
Author(s):  
Ashish Kothari ◽  
Vanya Singh ◽  
Uttam Kumar Nath ◽  
Sandeep Kumar ◽  
Vineeta Rai ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Performance ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Antigen Receptors ◽  
Multiple Treatment ◽  
Global Pandemic ◽  
Treatment Plans

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic threat with more than 11.8 million confirmed cases and more than 0.5 million deaths as of 3 July 2020. Given the lack of definitive pharmaceutical interventions against SARS-CoV-2, multiple therapeutic strategies and personal protective applications are being used to reduce the risk of high mortality and community spread of this infection. Currently, more than a hundred vaccines and/or alternative therapeutic regimens are in clinical trials, and some of them have shown promising results in improving the immune cell environment and controlling the infection. In this review, we discussed high-performance multi-directory strategies describing the uncontrolled deregulation of the host immune landscape associated with coronavirus disease (COVID-19) and treatment strategies using an anti-neoplastic regimen. We also followed selected current treatment plans and the most important on-going clinical trials and their respective outcomes for blocking SARS-CoV-2 pathogenesis through regenerative medicine, such as stem cell therapy, chimeric antigen receptors, natural killer (NK) cells, extracellular vesicular-based therapy, and others including immunomodulatory regimens, anti-neoplastic therapy, and current clinical vaccine therapy.

scholarly journals Pathophysiology of Perinatal Hypoxic-Ischemic Encephalopathy – Biomarkers, Animal Models and Treatment Perspectives

2016 ◽  
pp. S533-S545 ◽  
Author(s):  
V. RILJAK ◽  
J. KRAF ◽  
A. DARYANANI ◽  
P. JIRUŠKA ◽  
J. OTÁHAL
Keyword(s):  
Treatment Strategies ◽  
Hypoxic Ischemic Encephalopathy ◽  
Term Infants ◽  
Functional Deficits ◽  
Cellular Processes ◽  
General Outcome ◽  
Systemic Oxygen ◽  
Novel Treatment Strategies ◽  
Cellular Components ◽  
Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is one of the leading pediatric neurological conditions causing long-term disabilities and socio-economical burdens. Nearly 20-50 % of asphyxiated newborns with HIE die within the newborn period and another third will develop severe health consequences and permanent handicaps. HIE is the result of severe systemic oxygen deprivation and reduced cerebral blood flow, commonly occurring in full-term infants. Hypoxic-ischemic changes trigger several molecular and cellular processes leading to cell death and inflammation. Generated reactive oxygen species attack surrounding cellular components resulting in functional deficits and mitochondrial dysfunction. The aim of the present paper is to review present knowledge about the pathophysiology of perinatal hypoxic-ischemic encephalopathy, especially with respect to novel treatment strategies and biomarkers that might enhance early detection of this disorder and thus improve the general outcome of patients.

scholarly journals Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies

2021 ◽  
Vol 22 (6) ◽  
pp. 3142
Author(s):  
Inês Serrenho ◽  
Miguel Rosado ◽  
Alexandra Dinis ◽  
Carla M. Cardoso ◽  
Mário Grãos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cell ◽  
Cell Therapy ◽  
Umbilical Cord ◽  
Stem Cell Therapy ◽  
Perinatal Period ◽  
Hypoxic Ischemic Encephalopathy ◽  
Preclinical Studies ◽  
Mortality And Morbidity ◽  
Ischemic Encephalopathy

Neonatal hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in the perinatal period. This condition results from a period of ischemia and hypoxia to the brain of neonates, leading to several disorders that profoundly affect the daily life of patients and their families. Currently, therapeutic hypothermia (TH) is the standard of care in developing countries; however, TH is not always effective, especially in severe cases of HIE. Addressing this concern, several preclinical studies assessed the potential of stem cell therapy (SCT) for HIE. With this systematic review, we gathered information included in 58 preclinical studies from the last decade, focusing on the ones using stem cells isolated from the umbilical cord blood, umbilical cord tissue, placenta, and bone marrow. Outstandingly, about 80% of these studies reported a significant improvement of cognitive and/or sensorimotor function, as well as decreased brain damage. These results show the potential of SCT for HIE and the possibility of this therapy, in combination with TH, becoming the next therapeutic approach for HIE. Nonetheless, few preclinical studies assessed the combination of TH and SCT for HIE, and the existent studies show some contradictory results, revealing the need to further explore this line of research.

scholarly journals ANGI-10. CHEMOTHERAPEUTIC STRESS INDUCES TRANSDIFFERENTIATION OF GLIOBLASTOMA CELLS TO PROMOTE VASCULAR MIMICRY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi32-vi32
Author(s):  
Shivani Baisiwala ◽  
Brenda Auffinger ◽  
Seamus Caragher ◽  
Jack Shireman ◽  
Riasat Ahsan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ex Vivo ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Current Standard ◽  
Tube Forming ◽  
Key Factor ◽  
Orthotopic Xenografts

Abstract Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor affecting adults, with a median survival of approximately 21 months after diagnosis. A key factor underlying the limited efficacy of current treatment modalities is the remarkable plasticity exhibited by GBM cells, which allows them to effectively adapt to changes induced by our current treatment strategies. In addition to their plasticity, GBM tumors are also highly vascularized with aberrant vessels that further promote its aggressiveness. Recent research has demonstrated that GBM cells have the ability to transdifferentiate into endothelial cells (ECs), which suggests that GBM cells may use their properties of plasticity and vascularity in concert, leading to the creation of tumor-derived blood vessels. The mechanism behind this transdifferentiation remains unclear. Here, we show that treatment with temozolamide (TMZ)-based chemotherapy (the current standard of care) induces time-dependent increases in expression of markers for glioma stem cells (GSCs) and immature and mature ECs over 8 days of treatment (p < .001) in multiple patient-derived xenograft (PDX) lines. In addition, GBM tumors growing as orthotopic xenografts in nude mice showed significantly increased expression of GSC markers (CD15 and CD133) and EC markers (CD105 and CD144) after 8 days of TMZ treatment (p < .01). Ex-vivo FACS analysis of these orthotopic xenografts showed the presence of immature and mature EC populations in addition to GSC populations. To assess the functionality of these increased EC populations, a tube forming assay was performed. Results showed that the tube forming capacity of PDX lines was significantly increased (p < .01) after therapy. Furthermore, immunofluorescence analysis revealed increased tumor-derived vessels in TMZ-recurrent tumors. Overall, this study identifies chemotherapeutic stress as a new driver of transdifferentiation of tumor cells to endothelial cells and highlights cellular plasticity as a key player in therapeutic resistance and tumor recurrence.

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