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Experimental Physiology Dec 2019• What is the topic of this review? To explore the unique evolutionary origins of the human brain and critically appraise its energy budget, including limits of oxygen... (Review)
Review
NEW FINDINGS
• What is the topic of this review? To explore the unique evolutionary origins of the human brain and critically appraise its energy budget, including limits of oxygen and glucose deprivation during anoxia and ischaemia. • What advances does it highlight? The brain appears to be more resilient to substrate depletion than traditionally thought, highlighting greater resilience and an underappreciated capacity for functional recovery.
ABSTRACT
The human brain has evolved into an unusually large, complex and metabolically expensive organ that relies entirely on a continuous supply of O and glucose. It has traditionally been assumed that its exorbitant energy budget, combined with little to no energy reserves, renders it especially vulnerable to anoxia and ischaemia, with substrate depletion and progression towards cell death largely irreversible and rapid. However, new and exciting evidence suggests that neurons can survive for longer than previously thought, highlighting an unexpected resilience and underappreciated capacity for functional recovery that has changed the way we think about brain cell death. Nature has the potential to unlock some of the mysteries underlying ischaemic survival, with select vertebrates having solved the problem of anoxia-hypoxia tolerance over millions of years of evolution. Better understanding of their survival strategies, including remarkable adaptations in brain physiology and redox homeostasis, might help to identify new therapeutic targets for human diseases characterized by O deprivation, ischaemia-reperfusion injury and ageing.
Topics: Adaptation, Physiological; Animals; Brain Death; Energy Metabolism; Glucose; Humans; Hypoxia; Oxygen
PubMed: 31605408
DOI: 10.1113/EP088005 -
Philosophy, Ethics, and Humanities in... Oct 2021Brain death has been accepted worldwide medically and legally as the biological state of death of the organism. Nevertheless, the literature has described persistent... (Review)
Review
Brain death has been accepted worldwide medically and legally as the biological state of death of the organism. Nevertheless, the literature has described persistent problems with this acceptance ever since brain death was described. Many of these problems are not widely known or properly understood by much of the medical community. Here we aim to clarify these issues, based on the two intractable problems in the brain death debates. First, the metaphysical problem: there is no reason that withstands critical scrutiny to believe that BD is the state of biological death of the human organism. Second, the epistemic problem: there is no way currently to diagnose the state of BD, the irreversible loss of all brain functions, using clinical tests and ancillary tests, given potential confounders to testing. We discuss these problems and their main objections and conclude that these problems are intractable in that there has been no acceptable solution offered other than bare assertions of an 'operational definition' of death. We present possible ways to move forward that accept both the metaphysical problem - that BD is not biological death of the human organism - and the epistemic problem - that as currently diagnosed, BD is a devastating neurological state where recovery of sentience is very unlikely, but not a confirmed state of irreversible loss of all [critical] brain functions. We argue that the best solution is to abandon the dead donor rule, thus allowing vital organ donation from patients currently diagnosed as BD, assuming appropriate changes are made to the consent process and to laws about killing.
Topics: Brain Death; Death; Humans; Organ Transplantation; Tissue Donors; Tissue and Organ Procurement
PubMed: 34625089
DOI: 10.1186/s13010-021-00107-9 -
Neurology India 2022The determination of Brain Death (BD)/Death by neurological criteria (DNC) is now widely accepted among various international societies following the World Brain Death...
The determination of Brain Death (BD)/Death by neurological criteria (DNC) is now widely accepted among various international societies following the World Brain Death project recommendation. As per the World Brain Death project, ancillary testing should be performed when standard brain-death examination components are inconclusive or cannot be performed. BD was defined legally in 1994 under the Transplantation of Human Organs Act (THOA). However, even after 27 years of the formulated law, there are no guidelines in the THOA regarding the determination of BD using ancillary tests. The present brief report describes two instances where ancillary tests like four-vessel angiography and transcranial doppler-aided brain-death certification were done. It is the first available literature from our country where ancillary tests aided in confirmation of BD when the standard clinical components of DNC could not be performed.
Topics: Brain; Brain Death; Death Certificates; Humans; Neurologic Examination; Ultrasonography, Doppler, Transcranial
PubMed: 35864656
DOI: 10.4103/0028-3886.349609 -
Philosophy, Ethics, and Humanities in... Aug 2023The debate over the determination of death has been raging for more than fifty years. Since then, objections against the diagnosis of brain death from family members of...
The debate over the determination of death has been raging for more than fifty years. Since then, objections against the diagnosis of brain death from family members of those diagnosed as dead-have been increasing and are causing some countries to take novel steps to accommodate people's beliefs and preferences in the determination of death. This, coupled with criticism by some academics of the brain death criterion, raises some questions about the issues surrounding the determination of death. In this paper, we discuss some of the main approaches to death determination that have been theoretically proposed or currently put into practice and propose a new approach to death determination called "weak pluralism" as a reasonable ethical and political alternative to respect diversity in death determination.
Topics: Humans; Brain Death; Cultural Diversity; Bioethics
PubMed: 37528432
DOI: 10.1186/s13010-023-00139-3 -
Revista Brasileira de Terapia Intensiva 2019Brain death, defined as the complete and irreversible loss of brain functions, has a history that is linked to the emergence of intensive care units and the advancement... (Review)
Review
Brain death, defined as the complete and irreversible loss of brain functions, has a history that is linked to the emergence of intensive care units and the advancement of artificial ventilatory support. In Brazil, by federal law, the criteria for the diagnosis of brain death have been defined by the Federal Council of Medicine since 1997 and apply to the entire Brazilian territory. Resolution 2,173/2017 of the Federal Council of Medicine updated the criteria for diagnosing brain death. These changes include the following: the requirement for the patient to meet specific physiological prerequisites and for the physician to provide optimized care to the patient before starting the procedures for diagnosing brain death and to perform complementary tests, as well as the need for specific training for physicians who make this diagnosis. Other changes include the reduction of the time interval between the two clinical examinations, the possibility of continuing procedures in the presence of unilateral ear or eye injury, the performance of a single apnea test and the creation of a statement of brain death determination that includes the recording of all procedures in a single document. This document, despite the controversy surrounding it, increases the safety necessary when establishing a diagnosis of such importance and has positive implications that extend beyond the patient and the physician to reach the entire health system.
Topics: Brain Death; Brazil; Diagnostic Techniques and Procedures; Humans
PubMed: 31618361
DOI: 10.5935/0103-507X.20190050 -
Journal of Medical Ethics Mar 1990
Topics: Advisory Committees; Brain Death; Death; Humans; Personhood
PubMed: 2319571
DOI: 10.1136/jme.16.1.3 -
British Medical Journal Nov 1976
Topics: Brain Death; Humans
PubMed: 990821
DOI: No ID Found -
Transplant International : Official... 2023Organ transplantation after brain death is challenging in Nepal due to cultural beliefs, legal frameworks, and ethical considerations. The Human Body Organ... (Review)
Review
Organ transplantation after brain death is challenging in Nepal due to cultural beliefs, legal frameworks, and ethical considerations. The Human Body Organ Transplantation (Regulation and Prohibition) Act (HBOTA) has not met with substantial success after its amendment. This review critically appraises the current state of brain death and organ transplantation in Nepal. It explores challenges, evaluates progress, and provides recommendations. Literature review of databases was conducted to find articles on brain death, organ donation, and transplantation in Nepal. Analysis of cultural, legal, ethical, and practical factors influencing implementation. Key challenges include limited awareness, religious beliefs, infrastructure gaps, and family consent barriers. HBOTA amendments in 2016 enabled brain death donations, however, donation rates remain low. Strategies are needed to improve public education, resources, personnel training, and collaboration. Cultural sensitivity and stakeholder engagement are crucial. A multifaceted approach addressing cultural, legal, ethical and practical dimensions is essential to improve organ donation rates in Nepal. Despite progress, substantial challenges persist requiring evidence-based strategies focused on awareness, capacity building, policy improvements, and culturally appropriate community engagement.
Topics: Humans; Brain Death; Nepal; Organ Transplantation; Tissue and Organ Procurement; Religion
PubMed: 38089003
DOI: 10.3389/ti.2023.11882 -
Current Opinion in Organ Transplantation Jun 2019The current review presents a concise update on published literature on donation after circulatory death (DCD) and lung transplantation (LTx). Worldwide an increasing... (Review)
Review
PURPOSE OF REVIEW
The current review presents a concise update on published literature on donation after circulatory death (DCD) and lung transplantation (LTx). Worldwide an increasing need for lungs is evident, however the utilization rate of DCD lung donors is still considerably low. In this summary article, we reviewed both the experimental background and international clinical experience.
RECENT FINDINGS
Our analysis confirmed satisfactory results for LTx from DCD donors, which equals the results from donation after brain death. Although most studies reported on short-term results, some confirmed these results on the long-term and development of chronic lung allograft dysfunction. Our review summarizes the different DCD categories and underlines the potential of the DCD V category. We analyze the barriers to implement a DCD program, discuss the more recent advances like ex-vivo lung perfusion and describe the future challenges.
SUMMARY
Based on the current short-term and long-term clinical results, we believe that barriers for DCD utilization should be overcome, resulting in a safe implementation of more DCD LTx programs worldwide. VIDEO ABSTRACT.
Topics: Brain Death; Humans; Lung Transplantation; Middle Aged; Tissue Donors; Tissue and Organ Procurement
PubMed: 31090638
DOI: 10.1097/MOT.0000000000000627 -
Cell Death & Disease Jun 2015It is well known that most organs for transplantation are currently procured from brain-dead donors; however, the presence of brain death is an important risk factor in... (Review)
Review
It is well known that most organs for transplantation are currently procured from brain-dead donors; however, the presence of brain death is an important risk factor in liver transplantation. In addition, one of the mechanisms to avoid the shortage of liver grafts for transplant is the use of marginal livers, which may show higher risk of primary non-function or initial poor function. To our knowledge, very few reviews have focused in the field of liver transplantation using brain-dead donors; moreover, reviews that focused on both brain death and marginal grafts in liver transplantation, both being key risk factors in clinical practice, have not been published elsewhere. The present review aims to describe the recent findings and the state-of-the-art knowledge regarding the pathophysiological changes occurring during brain death, their effects on marginal liver grafts and summarize the more controversial topics of this pathology. We also review the therapeutic strategies designed to date to reduce the detrimental effects of brain death in both marginal and optimal livers, attempting to explain why such strategies have not solved the clinical problem of liver transplantation.
Topics: Brain Death; Humans; Liver; Liver Transplantation; Risk Factors; Tissue Donors; Tissue and Organ Procurement
PubMed: 26043077
DOI: 10.1038/cddis.2015.147