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Sample records for brain stem death

  1. Correlation between heat shock protein 70 expression in the brain stem and sudden death after experimental traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    ZHAO Lian-xu; XU Xiao-hu; LIU Chao; PAN Su-yue; ZHU Jia-zhen; ZHANG Cheng

    2001-01-01

    Objective: The aim of this study was to determine the patterns of heat-shock protein 70 (HSP70) biosynthesis following traumatic brain injury, and observe the effect of HSP70 induction on the function of the vital center in the brain stem. Methods: Rat models of sudden death resulted form traumatic brain injury were produced, and HSP70 expression in the rat brain stem was determined by immunohistochemistry, the induction of HSP70 mRNA detected by RT-PCR. Results: The level of HSP70 mRNA was prominently elevated in the brain stem as early as 1 5 min following the impact injury, while HSP70 expression was only observed 3 to 6 h after the injury. It was also observed that the levels of HSP70 mRNA but not the protein were elevated in the brain stem of sudden death rats. Conclusion: The synthesis of HSP70 was significantly enhanced in the brain stem following traumatic injury, and the expression of HSP70 is beneficial to eliminate the stress agents, and to sustain the cellular protein homeostasis. When the injury disturbs the synthesis of HSP70 to disarm the protective mechanism of heat-shock proteins, dysfunction of the vital center in the brain stem, and consequently death may occur. Breach in the synchronization of HSP70 mRNA-protein can be indicative of fatal damage to the nerve cells.

  2. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death.

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    Julie Y H Chan

    Full Text Available BACKGROUND: One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM. RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death. METHODOLOGY/PRINCIPAL FINDINGS: A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1, Ubc9 (the only known conjugating enzyme for the sumoylation pathway or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase. CONCLUSIONS

  3. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells.

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    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi; Shah, Khalid

    2015-06-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications.

  4. Brain death.

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    Wijdicks, Eelco F M

    2013-01-01

    The diagnosis of brain death should be based on a simple premise. If every possible confounder has been excluded and all possible treatments have been tried or considered, irreversible loss of brain function is clinically recognized as the absence of brainstem reflexes, verified apnea, loss of vascular tone, invariant heart rate, and, eventually, cardiac standstill. This condition cannot be reversed - not even partly - by medical or surgical intervention, and thus is final. Many countries in the world have introduced laws that acknowledge that a patient can be declared brain-dead by neurologic standards. The U.S. law differs substantially from all other brain death legislation in the world because the U.S. law does not spell out details of the neurologic examination. Evidence-based practice guidelines serve as a standard. In this chapter, I discuss the history of development of the criteria, the current clinical examination, and some of the ethical and legal issues that have emerged. Generally, the concept of brain death has been accepted by all major religions. But patients' families may have different ideas and are mostly influenced by cultural attitudes, traditional customs, and personal beliefs. Suggestions are offered to support these families.

  5. Brain stem death as the vital determinant for resumption of spontaneous circulation after cardiac arrest in rats.

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    Alice Y W Chang

    Full Text Available BACKGROUND: Spontaneous circulation returns to less than half of adult cardiac arrest victims who received in-hospital resuscitation. One clue for this disheartening outcome arises from the prognosis that asystole invariably takes place, after a time lag, on diagnosis of brain stem death. The designation of brain stem death as the point of no return further suggests that permanent impairment of the brain stem cardiovascular regulatory machinery precedes death. It follows that a crucial determinant for successful revival of an arrested heart is that spontaneous circulation must resume before brain stem death commences. Here, we evaluated the hypothesis that maintained functional integrity of the rostral ventrolateral medulla (RVLM, a neural substrate that is intimately related to brain stem death and central circulatory regulation, holds the key to the vital time-window between cardiac arrest and resumption of spontaneous circulation. METHODOLOGY/PRINCIPAL FINDINGS: An animal model of brain stem death employing the pesticide mevinphos as the experimental insult in Sprague-Dawley rats was used. Intravenous administration of lethal doses of mevinphos elicited an abrupt cardiac arrest, accompanied by elevated systemic arterial pressure and anoxia, augmented neuronal excitability and enhanced microvascular perfusion in RVLM. This period represents the vital time-window between cardiac arrest and resumption of spontaneous circulation in our experimental model. Animals with restored spontaneous circulation exhibited maintained neuronal functionality in RVLM beyond this critical time-window, alongside resumption of baseline tissue oxygen and enhancement of local blood flow. Intriguingly, animals that subsequently died manifested sustained anoxia, diminished local blood flow, depressed mitochondrial electron transport activities and reduced ATP production, leading to necrotic cell death in RVLM. That amelioration of mitochondrial dysfunction and

  6. The diagnosis of brain death

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    Goila Ajay

    2009-01-01

    Full Text Available Physicians, health care workers, members of the clergy, and laypeople throughout the world have accepted fully that a person is dead when his or her brain is dead. Although the widespread use of mechanical ventilators and other advanced critical care services have transformed the course of terminal neurologic disorders. Vital functions can now be maintained artificially for a long period of time after the brain has ceased to function. There is a need to diagnose brain death with utmost accuracy and urgency because of an increased awareness amongst the masses for an early diagnosis of brain death and the requirements of organ retrieval for transplantation. Physicians need not be, or consult with, a neurologist or neurosurgeon in order to determine brain death. The purpose of this review article is to provide health care providers in India with requirements for determining brain death, increase knowledge amongst health care practitioners about the clinical evaluation of brain death, and reduce the potential for variations in brain death determination policies and practices amongst facilities and practitioners. Process for brain death certification has been discussed under the following: 1. Identification of history or physical examination findings that provide a clear etiology of brain dysfunction. 2. Exclusion of any condition that might confound the subsequent examination of cortical or brain stem function. 3. Performance of a complete neurological examination including the standard apnea test and 10 minute apnea test. 4. Assessment of brainstem reflexes. 5. Clinical observations compatible with the diagnosis of brain death. 6. Responsibilities of physicians. 7. Notify next of kin. 8. Interval observation period. 9. Repeat clinical assessment of brain stem reflexes. 10. Confirmatory testing as indicated. 11. Certification and brain death documentation.

  7. Brain Death Determination.

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    Spinello, Irene M

    2015-09-01

    In the United States, each year 1% to 2% of deaths are brain deaths. Considerable variation in the practice of determining brain death still remains, despite the publication of practice parameters in 1995 and an evidence-based guideline update in 2010. This review is intended to give bedside clinicians an overview of definition, the causes and pitfalls of misdiagnosing brain death, and a focus on the specifics of the brain death determination process.

  8. Whither brain death?

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    Bernat, James L

    2014-01-01

    The publicity surrounding the recent McMath and Muñoz cases has rekindled public interest in brain death: the familiar term for human death determination by showing the irreversible cessation of clinical brain functions. The concept of brain death was developed decades ago to permit withdrawal of therapy in hopeless cases and to permit organ donation. It has become widely established medical practice, and laws permit it in all U.S. jurisdictions. Brain death has a biophilosophical justification as a standard for determining human death but remains poorly understood by the public and by health professionals. The current controversies over brain death are largely restricted to the academy, but some practitioners express ambivalence over whether brain death is equivalent to human death. Brain death remains an accepted and sound concept, but more work is necessary to establish its biophilosophical justification and to educate health professionals and the public.

  9. Hydrocephalus and Pressure on Brain Stem Cause Death in Patients with Neurofibromatosis Type 2

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    M. Khazaei

    2014-07-01

    Full Text Available Introduction: Neurofibromatosis type 2 is an inherited autosomal dominant syndrome, charac-terized by multiple neoplasms of the central and peripheral nervous system associated with ocular abnormalities. The most common tumor associated with the disease is the vestibulo-cochlear and in later stages are meningioma and other brain tumors. Case Report: The patient was a 35 year old woman admitted to the Farshchian hospital in Hamadan due to unconciousness and respiratory distress She had sensorineural hearing loss and inability to see due to decrease visulal acuity. In addition, due to lower extremity paresis she has been unable to walk and wheelchair-dependent for many years. Brain CT scan and MRI showed multiple tumors in the posterior fossa causing obstructive hydrocephalus even-tually caused the patient's death . Conclusion: Brain tumors, especially in the posterior fossa can cause death in Neurofibroma-tosis type 2. Early surgery can be life saving. (Sci J Hamadan Univ Med Sci 2014; 21 (2:167-170

  10. [Determination of brain death in organ donation: is EEG required?].

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    Kompanje, Erwin J O; Epker, Jelle L; de Groot, Yorick J; Wijdicks, Eelco F M; van der Jagt, Mathieu

    2013-01-01

    The determination of brain death is a prerequisite of multiple organ donation in ventilated patients in the ICU. The criteria for brain death differ internationally. In some countries, brain stem death is equivalent to brain death. In others, including the Netherlands, in addition to the determination of brain stem death, an EEG must also be carried out to rule out cortex activity according to the criteria of "whole brain death". However, this does not prove that there is complete failure of all brain functions; indeed, EEG does not examine the subcortical brain. The Dutch Health Board has established that brain death is ruled out by rest activity in the cortex, but not by persistent subcortical activity. This is conceptually incorrect. The criteria for brain stem death fit better in practice than the criteria for whole brain death. Taking an EEG should therefore no longer be an obligation in establishing brain death, as is the case in many other countries.

  11. Pediatric brain death determination.

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    Mathur, Mudit; Ashwal, Stephen

    2015-04-01

    Clinical guidelines for the determination of brain death in children were first published in 1987. These guidelines were revised in 2011 under the auspices of the Society of Critical Care Medicine, the American Academy of Pediatrics, and the Child Neurology Society, and provide the minimum standards that must be satisfied before brain death can be declared in infants and children. After achieving physiologic stability and exclusion of confounders, two examinations including apnea testing separated by an observation period (24 hours for term newborns up to 30 days of age, and 12 hours for infants and children from 31 days up to 18 years) are required to establish brain death. Apnea testing should demonstrate a final arterial PaCO2 20 mm Hg above the baseline and ≥ 60 mm Hg with no respiratory effort during the testing period. Ancillary studies (electroencephalogram and radionuclide cerebral blood flow) are not required to establish brain death and are not a substitute for the neurologic examination. The committee concluded that ancillary studies may be used (1) when components of the examination or apnea testing cannot be completed, (2) if uncertainty about components of the neurologic examination exists, (3) if a medication effect may be present, or (4) to reduce the interexamination observation period. When ancillary studies are used, a second clinical examination and apnea test should still be performed and components that can be completed must remain consistent with brain death.

  12. Diagnosis of brain death

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    Calixto Machado

    2010-06-01

    Full Text Available Brain death (BD should be understood as the ultimate clinical expression of a brain catastrophe characterized by a complete and irreversible neurological stoppage, recognized by irreversible coma, absent brainstem reflexes, and apnea. The most common pattern is manifested by an elevation of intracranial pressure to a point beyond the mean arterial pressure, and hence cerebral perfusion pressure falls and, as a result, no net cerebral blood flow is present, in due course leading to permanent cytotoxic injury of the intracranial neuronal tissue. A second mechanism is an intrinsic injury affecting the nervous tissue at a cellular level which, if extensive and unremitting, can also lead to BD. We review here the methodology of diagnosing death, based on finding any of the signs of death. The irreversible loss of cardio-circulatory and respiratory functions can cause death only when ischemia and anoxia are prolonged enough to produce an irreversible destruction of the brain. The sign of such loss of brain functions, that is to say BD diagnosis, is fully reviewed.

  13. Brain death is not death: a critique of the concept, criterion, and tests of brain death.

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    Joffe, Ari R

    2009-01-01

    This paper suggests that there are insurmountable problems for brain death as a criterion of death. The following are argued: (1) brain death does not meet an accepted concept of death, and is not the loss of integration of the organism as a whole; (2) brain death does not meet the criterion of brain death itself; brain death is not the irreversible loss of all critical functions of the entire brain; and (3) brain death may, however rarely, be reversible. I conclude that brain death, while a devastating neurological state with a dismal prognosis, is not death.

  14. [Brain death: biological and ethical aspects].

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    Roczeń, R; Bohatyrewicz, R

    2001-01-01

    The article presents briefly historical development of death criteria from the modern times to the present. The criteria which are used for identification and diagnosing death on the base of respiratory and circulatory death definition are described. This work underlines the inadequacy of the definition of the brain death in relation to patients with persistent vegetative state and in relation to anencephalic newborns. The author describes the pathology and clinical and laboratory evidence of the brain stem death, which gave the possibility to justify the thesis that in case of the brain stem death ontological arguments are sufficient for diagnosing the death of a human being. The attention of the ethic of the life sanctity (on the base of halachic's law) and its opposing influence on the evolution of the medical definition of death has been paid. The recognition of the brain as the death of an individual is a cultural shock, which from scientific point of view changed the ways of thinking, almost immediately but did not in the awareness of the society. The work also underlies the fact that utilitarian argumentation can not be a criterion for making a decision concerning the life of an individual.

  15. Scintigraphic evaluation of brain death

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    Park, C. H.; Bai, M. S.; Cho, K. K.; Kim, S. J.; Yoon, S. N.; Cho, C. W. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1997-07-01

    A law recognizing brain death is a life saving legal measure in patients suffering from badly diseased organs such as kidney, liver, heart, and lung. Such law is being discussed for legalization at the Korean National Assembly. There are various criteria used for brain death in western world and brain scintiscan is one of them. However, the scintiscan is not considered in establishing brain death in the draft of the law. The purpose of this report is to spread this technique in nuclear medicine society as well as in other medical societies. We evaluated 7 patients with clinical suspicion of brain death by various causes. The patient's age ranged from 5 to 39 years. We used 5-20mCi {sup 99m}Tc-HMPAO (d.1-hexamethyl propylene amine oxime) or ECD (Ethyl Cysteinate Dimer), lipophilic agents that cross BBB (blood brain barrier). A dynamic study followed by static or SPECT (single photon emission tomography) was performed. Interpretive criteria used for brain death were 1) no intracranial circulation 2) no brain uptake. The second criteria is heavily used. Five of 7 patients were scintigraphically brain dead and the remaining 2 had some brain uptake excluding the diagnosis of scintigraphic brain death. In conclusion, cerebral perfusion study using a lipophilic brain tracer offers a noninvasive, rapid, easy, accurate and reliable mean in the diagnosis of brain death. We believe that this modality should be included in the criteria of brain death in the draft of the proposed Korean law.

  16. Brain death: the European perspective.

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    Citerio, Giuseppe; Murphy, Paul G

    2015-04-01

    Some of the seminal steps toward the recognition and definition of brain death were European. There is a general consensus on both the medical concept of brain death in Europe as well as the minimum fundamental clinical standards that are required for its diagnosis-the absence of consciousness, brainstem reflexes, and the ability to breathe in the absence of reversible or confounding conditions. Two aspects of brain death determination are addressed in this article. The authors analyze how brain death is diagnosed across Europe, identifying both the similarities and differences that exist between countries (the latter mainly concerning ancillary tests, timing, and the number of physicians involved in the brain death determination). In addition, they describe the very considerable variations in when brain death determinations are made between and within individual European countries, and propose that they are due to differences in the end-of-life care practices in patients with irreversible brain injuries, medical attitudes, and organ donation practices. Although legislation is available to standardize the brain death diagnosis process in most individual European countries, there are still disparities across Europe as a whole. The current variation in practice makes a continental consensus for the definition of brain death imperative.

  17. Brain death: the Asian perspective.

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    Chua, Hoe Chin; Kwek, Tong Kiat; Morihara, Hirofumi; Gao, Daiquan

    2015-04-01

    Asia is the largest and most populous continent in the world with people from many diverse ethnic groups, religions and government systems. The authors surveyed 14 countries accounting for the majority of Asia's population and found that, although the concept of brain death is widely accepted, there is wide variability in the criteria for certification. Although most Asian countries have adopted the "whole-brain" concept of brain death, most countries with past colonial links to the United Kingdom follow the UK "brainstem" concept of brain death. Despite this difference, most countries require only neurologic testing of irreversible coma and absent brainstem reflexes as criteria for certification of brain death. Variability exists in the number of personnel required, qualifications of certifying doctors, need for repeat examination, minimum time interval between examinations, and requirement for and choice of confirmatory tests.

  18. Spinal reflexes in brain death.

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    Beckmann, Yesim; Çiftçi, Yeliz; Incesu, Tülay Kurt; Seçil, Yaprak; Akhan, Galip

    2014-12-01

    Spontaneous and reflex movements have been described in brain death and these unusual movements might cause uncertainties in diagnosis. In this study we evaluated the presence of spinal reflexes in patients who fulfilled the criteria for brain death. Thirty-two (22 %) of 144 patients presented unexpected motor movements spontaneously or during examinations. These patients exhibited the following signs: undulating toe, increased deep tendon reflexes, plantar responses, Lazarus sign, flexion-withdrawal reflex, facial myokymia, neck-arm flexion, finger jerks and fasciculations. In comparison, there were no significant differences in age, sex, etiology of brain death and hemodynamic laboratory findings in patients with and without reflex motor movement. Spinal reflexes should be well recognized by physicians and it should be born in mind that brain death can be determined in the presence of spinal reflexes.

  19. Brain Death,Concept and Criteria

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The concept of brain death originated in France. In 1959, the French scholars P. Mollaret and M. Goulon proposed the concept of "coma de- passe" or "brain death" for the first time and reported 23 cases with such symptoms. The first guidelines (the Harvard criteria) for diagnosing brain death was established in 1968, defining brain death

  20. Ancillary testing in brain death.

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    Kramer, Andreas H

    2015-04-01

    Despite worldwide acceptance of the concept of brain death, there is marked variability in the use of ancillary testing. In most countries, ancillary tests are used primarily when confounding factors interfere with reliable completion of a clinical assessment, or physiologic instability precludes performance of an apnea test. Alternatively, in some countries, confirmatory ancillary tests are routinely required before brain death can be diagnosed. Ancillary tests assess brain function (e.g., electroencephalography) or blood flow (e.g., cerebral angiography). Evaluation of blood flow is affected less by confounding clinical factors and is now preferred in most jurisdictions. With angiographic techniques, a significant proportion of patients meeting clinical criteria for brain death have some opacification of proximal intracranial arteries. Consequently, the sensitivity of angiography is strongly influenced by the particular criteria that are used to define intracranial circulatory arrest. Lack of enhancement of the great cerebral and internal cerebral veins has the highest sensitivity. Worldwide experience with newer tests, such as computed tomography and magnetic resonance angiography, is growing. Radionuclide imaging has the advantage of not requiring use of potentially nephrotoxic contrast material. Transcranial Doppler ultrasonography can be brought to the bedside to demonstrate lack of brain blood flow. The specificity of imaging techniques in the detection of intracranial circulatory arrest has not been as well studied as their sensitivity.

  1. Changing the conversation about brain death.

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    Truog, Robert D; Miller, Franklin G

    2014-01-01

    We seek to change the conversation about brain death by highlighting the distinction between brain death as a biological concept versus brain death as a legal status. The fact that brain death does not cohere with any biologically plausible definition of death has been known for decades. Nevertheless, this fact has not threatened the acceptance of brain death as a legal status that permits individuals to be treated as if they are dead. The similarities between "legally dead" and "legally blind" demonstrate how we may legitimately choose bright-line legal definitions that do not cohere with biological reality. Not only does this distinction bring conceptual coherence to the conversation about brain death, but it has practical implications as well. Once brain death is recognized as a social construction not grounded in biological reality, we create the possibility of changing the social construction in ways that may better serve both organ donors and recipients alike.

  2. [Brain death--a certain sign of death].

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    Angstwurm, H

    1990-10-01

    Brain death means a complete and irreversible loss of all brain activity during intensive care with mechanical ventilation. On autopsy is seen an ischemic infarct of the whole brain following the stopped blood flow in the intracranial cavity after the elevation of the pressure. With brain death a human being loses two characteristics of its earthly life, the physical base needed for his spirit and his soul in this world, and the integration, the unity as the independent and self-contained organism.

  3. Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein kinase at rostral ventrolateral medulla in experimental brain stem death

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    Chang Alice YW

    2012-11-01

    Full Text Available Abstract Background Based on an experimental brain stem death model, we demonstrated previously that activation of the mitogen-activated protein kinase kinase 1/2 (MEK1/2/extracellular signal-regulated kinase 1/2 (ERK1/2/mitogen-activated protein kinase signal-interacting kinase 1/2 (MNK1/2 cascade plays a pro-life role in the rostral ventrolateral medulla (RVLM, the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life and decreases (pro-death to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients. The present study assessed the hypothesis that, in addition to ERK1/2, c-Jun NH2-terminal kinase (JNK and p38 mitogen-activated protein kinase (p38MAPK, the other two mammalian members of MAPKs that are originally identified as stress-activated protein kinases, are activated specifically by MAPK kinase 4 (MAP2K4 or MAP2K6 and play a pro-life role in RVLM during experimental brain stem death. We further delineated the participation of phosphorylating activating transcriptional factor-2 (ATF-2 and c-Jun, the classical transcription factor activated by JNK or p38MAPK, in this process. Results An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol bilaterally into RVLM of Sprague–Dawley rats was used, alongside cardiovascular, pharmacological and biochemical evaluations. Results from ELISA showed that whereas the total JNK, p38MAPK, MAP2K4 and MAP2K6 were not affected, augmented phosphorylation of JNK at Thr183 and Tyr185 and p38MAPK at Thr180 and Tyr182, accompanied by phosphorylation of their upstream activators MAP2K4 at Ser257 and Thr261 and MAP2K6 at Ser207 and Thr211 in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Moreover, the activity of transcription factors ATF-2 at Thr71 and

  4. Simulation training in brain death determination.

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    Hocker, Sara; Wijdicks, Eelco F M

    2015-04-01

    Skill in the determination of brain death is traditionally acquired during training in an apprenticeship model. Brain death is not frequently determined, and thus exposure to the techniques used is marginal. Brain death is therefore ideally suited for competency-based education models such as simulation. Simulation can ensure that all trainees have direct experience in brain death determination irrespective of their specialty, program design, or institutional protocol. In this review, the authors discuss the advantages and barriers to simulation and how to develop simulation scenarios for instruction in the determination of brain death. Future research should focus on validation of brain death simulation methods and assessment tools as well as the impact of simulation on performance in clinical practice.

  5. History of brain death as death: 1968 to the present.

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    De Georgia, Michael A

    2014-08-01

    The concept of brain death was formulated in 1968 in the landmark report A Definition of Irreversible Coma. While brain death has been widely accepted as a determination of death throughout the world, many of the controversies that surround it have not been settled. Some may be rooted in a misconstruction about the history of brain death. The concept evolved as a result of the convergence of several parallel developments in the second half of the 20th century including advances in resuscitation and critical care, research into the underlying physiology of consciousness, and growing concerns about technology, medical futility, and the ethics of end of life care. Organ transplantation also developed in parallel, and though it clearly benefited from a new definition of death, it was not a principal driving force in its creation. Since 1968, the concept of brain death has been extensively analyzed, debated, and reworked. Still there remains much misunderstanding and confusion, especially in the general public. In this comprehensive review, I will trace the evolution of the definition of brain death as death from 1968 to the present, providing background, history and context.

  6. Selection of reference genes for normalisation of real-time RT-PCR in brain-stem death injury in Ovis aries

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    Fraser John F

    2009-07-01

    Full Text Available Abstract Background Heart and lung transplantation is frequently the only therapeutic option for patients with end stage cardio respiratory disease. Organ donation post brain stem death (BSD is a pre-requisite, yet BSD itself causes such severe damage that many organs offered for donation are unusable, with lung being the organ most affected by BSD. In Australia and New Zealand, less than 50% of lungs offered for donation post BSD are suitable for transplantation, as compared with over 90% of kidneys, resulting in patients dying for lack of suitable lungs. Our group has developed a novel 24 h sheep BSD model to mimic the physiological milieu of the typical human organ donor. Characterisation of the gene expression changes associated with BSD is critical and will assist in determining the aetiology of lung damage post BSD. Real-time PCR is a highly sensitive method involving multiple steps from extraction to processing RNA so the choice of housekeeping genes is important in obtaining reliable results. Little information however, is available on the expression stability of reference genes in the sheep pulmonary artery and lung. We aimed to establish a set of stably expressed reference genes for use as a standard for analysis of gene expression changes in BSD. Results We evaluated the expression stability of 6 candidate normalisation genes (ACTB, GAPDH, HGPRT, PGK1, PPIA and RPLP0 using real time quantitative PCR. There was a wide range of Ct-values within each tissue for pulmonary artery (15–24 and lung (16–25 but the expression pattern for each gene was similar across the two tissues. After geNorm analysis, ACTB and PPIA were shown to be the most stably expressed in the pulmonary artery and ACTB and PGK1 in the lung tissue of BSD sheep. Conclusion Accurate normalisation is critical in obtaining reliable and reproducible results in gene expression studies. This study demonstrates tissue associated variability in the selection of these

  7. Brain death: legal obligations and the courts.

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    Burkle, Christopher M; Pope, Thaddeus M

    2015-04-01

    Brain death, or death determined by neurologic criteria, has been legally adopted in all U.S. states for decades. Despite its long-established history, a lack of clear understanding has led to disputes requiring a legal forum for resolution. Recently, physicians and hospitals across the country have been impacted by a growing number of disputes about brain death. The authors offer clinicians a historical perspective on the evolution of brain death as a legal cause of death in the United States. They then review the more common legal categories of disputes encountered, including representative court cases for each. This overview provides physicians with a general legal perspective on brain death so they may better appreciate the pertinent issues if and when later confronted.

  8. Brain death and organ donation of children.

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    Gündüz, Ramiz Coşkun; Şahin, Şanlıay; Uysal-Yazıcı, Mutlu; Ayar, Ganime; Yakut, Halil İbrahim; Akman, Alkım Öden; Hirfanoğlu, İbrahim Murat; Kalkan, Gökhan

    2014-01-01

    We aimed to define the demographic characteristics, clinical features and outcome of patients with brain death, and to emphasize the importance of organ donation from children. Data for the period from September 2009 to October 2012 were collected retrospectively. Twenty children who were diagnosed as brain death were included. Data including demographics, major cause leading to brain death, duration of brain death evaluation, ancillary tests used to confirm brain death, complications and outcome, duration of hospitalization and organ donation were collected for statistical evaluation. The mean age was 6.2 years, and the male/female ratio 1.85. The major cause leading to brain death was most often traumatic brain injury, seen in 11 patients (55%). The mean duration of brain death evaluation was 6.7 and 1.7 days in Centers I and II respectively. The mean duration of hospitalization was 12.5 days. Electroencephalography (EEG) was used in 18 patients (90%). Complications included hyperglycemia in 13 cases and diabetes incipitus in 7 cases (65% and 35%, respectively). Mean duration of survival was 9.8 days. In Center I, one of the patients' parents gave consent to organ donation, while four parents in Center II agreed to organ donation. The study demonstrated that the duration of brain death evaluation was longer in Center I than in Center II (pbrain death and length of stay in the PICU (p>0.05). Early diagnosis of brain death and prompt evaluation of patients by ICU physicians once the diagnosis is taken into consideration will probably yield better organs and reduce costs. Training PICU physicians, nurses and organ donation coordinators, and increasing children's awareness of the need for organ donation via means of public communication may increase families' rate of agreement to organ donation in the future.

  9. Reviving brain death: a functionalist view.

    Science.gov (United States)

    Lipuma, Samuel H; DeMarco, Joseph P

    2013-10-01

    Recently both whole brain death (WBD) and higher brain death (HBD) have come under attack. These attacks, we argue, are successful, leaving supporters of both views without a firm foundation. This state of affairs has been described as "the death of brain death." Returning to a cardiopulmonary definition presents problems we also find unacceptable. Instead, we attempt to revive brain death by offering a novel and more coherent standard of death based on the permanent cessation of mental processing. This approach works, we claim, by being functionalist instead of being based in biology, consciousness, or personhood. We begin by explaining why an objective biological determination of death fails. We continue by similarly rejecting current arguments offered in support of HBD, which rely on consciousness and/or personhood. In the final section, we explain and defend our functionalist view of death. Our definition centers on mental processing, both conscious and preconscious or unconscious. This view provides the philosophical basis of a functional definition that most accurately reflects the original spirit of brain death when first proposed in the Harvard criteria of 1968.

  10. Medical and ethical dilemma in brain death.

    Science.gov (United States)

    Streba, Irina; Damian, Simona; Ioan, Beatrice

    2012-01-01

    For centuries, death has been defined, medically speaking, as the irreversible cessation of breathing and of nervous and cardiac activity. What radically changed this definition was the introduction of the concept "brain death" in 1968, by the "Ad Hoc Committee of the Harvard Medical School". According to it, the irreversible coma was associated with brain death and considered to be a criterion for the diagnosis of the deceased individual. The evergrowing need for transplant organs (provided this respects the dead honor rule, stipulating that organs can't be harvested unless someone is deceased) lead to making arbitrary decisions regarding the establishment of the exact time of death during the process of "losing life". What actually triggers the controversy related to the concept of brain death is the dilemma of associating this concept with that of biologic death or death of the person, the difference between the two being made by whether the mental characteristics are accepted or not in defining and individualizing the death of the human being. Given these circumstances, a dilemma appears--that of defining the death of the individual: we define death, as it has been for centuries, as the moment when the cardio-respiratory function no longer exists, which leads to the loss of tens of thousands of lives that might have been saved through transplant. Yet, this may lead to manipulating the border between life and death, with the risk of trespassing each individual's right to life.

  11. Magnetic resonance imaging of brain death

    Energy Technology Data Exchange (ETDEWEB)

    Lee, D.H.; Nathanson, J.A.; Fox, A.J.; Pelz, D.M.; Lownie, S.P.

    1995-06-01

    In order to demonstrate the magnetic resonance imaging (MRI) appearance of the brain in patients with clinical brain death, high-field MRI was performed on 5 patients using conventional T1-weighted and T2-weighted imaging. The study showed MRI exhibited similar features for all of the patients, features which were not found in MRI of comatose patients who were not clinically brain dead. It was stated that up to now the most important limitation in MRI of patients with suspected brain death has been the extreme difficulty of moving them out of the intensive care setting. If this problem can be overcome, and it appears possible with with the advent of MRI-compatible ventilators and noninvasive monitoring, MRI could become an excellent alternative for confirming clinical diagnosis of brain death for such patients. 15 refs., 3 figs.

  12. Brain death dilemmas and the use of ancillary testing.

    Science.gov (United States)

    Webb, Adam; Samuels, Owen

    2012-06-01

    The Uniform Determination of Death Act indicates that "an individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead," with brain death being determined based on "accepted medical standards." The AAN has published practice guidelines providing medical standards for the determination of brain death. The most recent AAN guideline update notes that "because of the deficiencies in the evidence base, clinicians must exercise considerable judgment when applying the criteria in specific circumstances" and that "ancillary tests can be used when uncertainty exists about the reliability of parts of the neurologic examination or when the apnea test cannot be performed. This article presents two cases commonly encountered in clinical practice in which the findings of the guideline-specified clinical neurologic assessment may be difficult to interpret, hampering the clinical determination of brain death. In these circumstances, ancillary testing specifically assessing for cerebral circulatory arrest may be helpful.

  13. The influence of brain death on liver function

    NARCIS (Netherlands)

    Olinga, Peter; Hoeven, Joost Alexander Boreas van der; Merema, M.T.; Freund, R.L.; Ploeg, R.J; Groothuis, Geny

    2005-01-01

    Background: In this study, we investigated the influence of brain death on inflammatory response and the effects of brain death on liver function both directly after explantation and after reoxygenation. Methods: The influence of brain death on liver function was studied in rats using a brain death

  14. Brain death: the United kingdom perspective.

    Science.gov (United States)

    Smith, Martin

    2015-04-01

    The United Kingdom (UK) has incorporated a brainstem formulation into its brain death criteria since the first guidelines were published in 1976. A clinical diagnosis incorporating three sequential but interdependent steps is sufficient for the determination of brain death in the UK. There must be no doubt that the patient's comatose condition is due to irreversible brain damage of known etiology, and potentially reversible causes of coma and apnea, such as drug effects, metabolic or endocrine disturbances, or hypothermia, must be excluded. A clinical examination of brainstem reflexes and an apnea test is then undertaken. Confirmatory tests are not required in the UK, but may be useful to reduce any element of uncertainty or minimize the period of observation prior to the diagnosis of brainstem death if the preconditions for clinical testing are not met, or if a comprehensive neurologic examination is not possible. Brainstem death must be diagnosed by two doctors who must be present at each of the two sets of clinical tests that are required to determine death. Although death is not confirmed until the second test has been completed, the legal time of death is when the first test confirms the absence of brainstem reflexes.

  15. EEG abnormalities in clinically diagnosed brain death organ donors in Iranian tissue bank.

    Science.gov (United States)

    Tavakoli, Seyed Amir Hossein; Khodadadi, Abbas; Azimi Saein, Amir Reza; Bahrami-Nasab, Hasan; Hashemi, Behnam; Tirgar, Niloufar; Nozary Heshmati, Behnaz

    2012-01-01

    Brain death is defined as the permanent, irreversible and concurrent loss of all brain and brain stem functions. Brain death diagnosis is based on clinical criteria and it is not routine to use paraclinical studies. In some countries, electroencephalogram (EEG) is performed in all patients for the determination of brain death while there is some skepticism in relying on EEG as a confirmatory test for brain death diagnosis. In this study, we assessed the validity of EEG and its abnormalities in brain death diagnosis. In this retrospective study, we used 153 EEGs from medical records of 89 brain death patients in organ procurement unit of the Iranian Tissue Bank admitted during 2002-2008. We extracted and analyzed information including EEGs, which were examined by a neurologist for waves, artifacts and EEG abnormalities. The mean age of the patients was 27.2±12.7 years. The most common cause of brain death was multiple traumas due to accident (65%). The most prevalent artifact was electrical transformer. 125 EEGs (82%) were isoelectric (ECS) and seven EEGs (5%) were depictive of some cerebral activity which upon repeat EEGs, they showed ECS patterns too. There was no relationship between cause of brain death and cerebral activity in EEGs of the patients. In this study, we could confirm ECS patterns in all brain death patients whose status had earlier been diagnosed clinically. Considering the results of this study, it seems sensible to perform EEG as a final confirmatory test as an assurance to the patients' families.

  16. Pediatric brain death: updated guidelines.

    Science.gov (United States)

    Mullen, Jodi E

    2013-01-01

    Logan, a 5-year-old boy, was riding his bike with his 7-year-old brother when he was struck from behind by a car traveling at approximately 40 mph. The driver indicated that she did not see the riders until she hit Logan, who was not wearing a helmet at the time of the accident. Logan was thrown from his bike and was found at the side of the road, unresponsive and posturing. Although he was uninjured, Logan's brother witnessed the incident.Emergency medical services arrived and placed Logan on a backboard with a c-collar. Because he was not protecting his airway, he was intubated and then given sodium chloride fluids and brought to the pediatric emergency department. Upon arrival, his Glasgow Coma Scale score was 5, and his right pupil was 6 mm and not reactive.Logan's initial head computed tomographic scan showed diffuse brain edema, with early downward transtentorial brain herniation. The pediatric neurosurgeon determined that no operative management was appropriate for Logan. Besides a small laceration on his forehead, Logan had no other injuries. At this time, he was taking a few spontaneous respirations and had occasional posturing of his extremities.

  17. Approach of Complex Networks for the Determination of Brain Death

    Science.gov (United States)

    Sun, Wei-Gang; Cao, Jian-Ting; Wang, Ru-Bin

    2011-06-01

    In clinical practice, brain death is the irreversible end of all brain activity. Compared to current statistical methods for the determination of brain death, we focus on the approach of complex networks for real-world electroencephalography in its determination. Brain functional networks constructed by correlation analysis are derived, and statistical network quantities used for distinguishing the patients in coma or brain death state, such as average strength, clustering coefficient and average path length, are calculated. Numerical results show that the values of network quantities of patients in coma state are larger than those of patients in brain death state. Our findings might provide valuable insights on the determination of brain death.

  18. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    Institute of Scientific and Technical Information of China (English)

    Guanqun Qiao; Qingquan Li; Gang Peng; Jun Ma; Hongwei Fan; Yingbin Li

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are stil unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cel s and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cel s were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibril ary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibril ary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibril ary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cel s. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

  19. A Response to the Legitimacy of Brain Death in Islam.

    Science.gov (United States)

    Rady, Mohamed Y; Verheijde, Joseph L

    2016-08-01

    Brain death is a novel construct of death for the procurement of transplantable organs. Many authoritative Islamic organizations and governments have endorsed brain death as true death for organ donation. Many commentators have reiterated the misconception that the Quranic text does not define death. We respond by clarifying: (1) the Quran does define death as biologic disintegration and clearly distinguishes it from the dying process, (2) brain death belongs scientifically within the spectrum of neurologic disorders of consciousness and should not be confused with death, and (3) religious and legal discord about brain death has grown in jurisdictions worldwide. We urge for public transparency and truthfulness about brain death and the accommodation and respect of religious objection to the determination of death by neurologic criteria.

  20. Approach of Complex Networks for the Determination of Brain Death

    Institute of Scientific and Technical Information of China (English)

    SUN Wei-Gang; CAO Jian-Ting; WANG Ru-Bin

    2011-01-01

    In clinical practice, brain death is the irreversible end of all brain activity. Compared to current statistical methods for the determination of brain death, we focus on the approach of complex networks for real-world electroencephalography in its determination. Brain functional networks constructed by correlation analysis are derived, and statistical network quantities used for distinguishing the patients in coma or brain death state, such as average strength, clustering coefficient and average path length, are calculated. Numerical results show that the values of network quantities of patients in coma state are larger than those of patients in brain death state. Our Sndings might provide valuable insights on the determination of brain death.%@@ In clinical practice, brain death is the irreversible end of all brain activity.Compared to current statistical methods for the determination of brain death, we focus on the approach of complex networks for real-world electroencephalography in its determination.Brain functional networks constructed by correlation analysis axe derived, and statistical network quantities used for distinguishing the patients in coma or brain death state, such as average strength, clustering coefficient and average path length, are calculated.Numerical results show that the values of network quantities of patients in coma state are larger than those of patients in brain death state.Our findings might provide valuable insights on the determination of brain death.

  1. Brain death in neonates: a case report

    Directory of Open Access Journals (Sweden)

    Georgios Mitsiakos

    2014-06-01

    Full Text Available Brain death (BD is the permanent and complete loss of cerebral and brainstem function. It is relatively uncommon in newborns with its percentage among deaths being 1-6.3%. BD leads to debate for medical, ethical and philosophical issues. It is a challenging condition in neonatal intensive care units (NICUs since difficulties for BD diagnosis in neonates and ever more so in preterm neonates do arise. Revised guidelines for BD diagnosis definition include history with known etiology, clinical examination, apnea testing and neurological evaluation often assisted by ancillary tests. We present the case of a near term female baby that was born with brain death due to hypoxic ischemic encephalopathy. We conclude that BD in newborns is a challenge to NICUs and there is a need for establishing and implementing new guidelines and checklists on national basis. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  2. Cerebral and brain stem Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Breidahl, W.H. (Dept. of Radiology, Royal Perth Hospital, Nedlands (Australia)); Ives, F.J. (Dept. of Radiology, Royal Perth Hospital, Nedlands (Australia)); Khangure, M.S. (Dept. of Magnetic Resonance Imaging, Sir Charles Gairdner Hospital, Nedlands (Australia))

    1993-05-01

    Two patients with central nervous system manifestations of Langerhans cell histiocytosis, both with brain stem involvement, are reported. The onset of symptoms was at an age when the diagnosis might not have been considered. (orig.)

  3. Revisiting the Persisting Tension Between Expert and Lay Views About Brain Death and Death Determination: A Proposal Inspired by Pragmatism.

    Science.gov (United States)

    Racine, Eric

    2015-12-01

    Brain death or determination of death based on the neurological criterion has been an enduring source of controversy in academic and clinical circles. The controversy chiefly concerns how death is defined, and it also bears on the justification of the proposed criteria for death determination and their interpretation. Part of the controversy on brain death and death determination stems from disputed crucial medical facts, but in this paper I formulate another hypothesis about the nature of ongoing controversies. At stake is a misunderstood relationship between, on the one hand, the nature of our lay (or our "manifest image") views about death and, on the other hand, the nature of scientific insights (and related conceptual refinements) into death and its determination (the "scientific image"). The misunderstanding of this relationship has partly anchored the controversy and continues to fuel it. Based on a perspective inspired by pragmatism, which stresses the positive contribution of science to ethical and policy debates but also challenges different forms of scientism in science and philosophy found in foundationalist interpretations, I scrutinize three different stances regarding the relationship between lay and scientific perspectives about the definition of death: (1) foundational lay views, (2) foundational expert views, and (3) co-evolving views. I argue that only the latter is sustainable given recent challenges to foundationalist interpretations.

  4. Stem cells to regenerate the newborn brain

    NARCIS (Netherlands)

    van Velthoven, C.T.J.

    2011-01-01

    Perinatal hypoxia-ischemia (HI) is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. In this thesis we investigate whether mesenchymal stem cells (MSC) regenerate the neonatal brain after HI injury. We show that transplantation of MSC after neonatal brain injury

  5. Distinct transcriptional changes in donor kidneys upon brain death induction in rats : Insights in the processes of brain death

    NARCIS (Netherlands)

    Schuurs, TA; Gerbens, F; van der Hoeven, JAB; Ottens, PJ; Kooi, KA; Leuvenink, HGD; Hofstra, RMW; Ploeg, RJ

    2004-01-01

    Brain death affects hormone regulation, inflammatory reactivity and hemodynamic stability. In transplant models, donor organs retrieved from brain dead (BD) rats suffer from increased rates of primary nonfunction and lower graft survival. To unravel the mechanisms behind brain death we have performe

  6. Temperature and brain death determination: need for updated criteria

    Directory of Open Access Journals (Sweden)

    Michael A. Meyer

    2010-08-01

    Full Text Available For an excellent review on the diagnosis of brain death, the interested reader is directed to the review of Machado appearing in this journal; the author reviews all aspects of brain death and cites nine different references where the minimum temperature for brain death exams appear to have been at least 32°C. Given the new data listed above, it is clearly time for a reconsideration of the how we approach the exam for diagnosis of brain death – normal or near normal temperatures of 36°C and above are very reasonable starting points.

  7. Stem cell death and survival in heart regeneration and repair.

    Science.gov (United States)

    Abdelwahid, Eltyeb; Kalvelyte, Audrone; Stulpinas, Aurimas; de Carvalho, Katherine Athayde Teixeira; Guarita-Souza, Luiz Cesar; Foldes, Gabor

    2016-03-01

    Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.

  8. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    Science.gov (United States)

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-04-21

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases.

  9. 99mTc-HMPAO perfusion SPECT/CT in the diagnosis of brain death.

    Science.gov (United States)

    Derlin, Thorsten; Weiberg, Desiree

    2016-01-01

    This report describes a case of brain death (BD) evaluated by 99mTc-hexamethylpropylene amine oxime (HMPAO) single photon emission tomography/computed tomography (SPECT/CT). A 16-year-old boy with a history of rapid unexpected brain herniation due to pilocytic astrocytoma underwent 99mTc-HMPAO SPECT/CT for evaluation of brain death in the context of organ donation. Flow images demonstrated lack of blood flow to the brain, and delayed images showed absence of demonstrable radionuclide activity within the brain. SPECT/CT confirmed absence of tracer accumulation, and was deemed helpful for evaluation of the brain stem. 99mTc-HMPAO SPECT/CT is a valuable tool enabling imaging-based confirmation of BD.

  10. Confounding factors in diagnosing brain death: a case report

    Directory of Open Access Journals (Sweden)

    Login Ivan S

    2002-06-01

    Full Text Available Abstract Background Brain death is strictly defined medically and legally. This diagnosis depends on three cardinal neurological features: coma, absent brainstem reflexes, and apnea. The diagnosis can only be made, however, in the absence of intoxication, hypothermia, or certain medical illnesses. Case presentation A patient with severe hypoxic-ischemic brain injury met the three cardinal neurological features of brain death but concurrent profound hypothyroidism precluded the diagnosis. Our clinical and ethical decisions were further challenged by another facet of this complex case. Although her brain damage indicated a hopeless prognosis, we could not discontinue care based on futility because the only known surrogate was mentally retarded and unable to participate in medical planning. Conclusion The presence of certain medical conditions prohibits a diagnosis of brain death, which is a medicolegal diagnosis of death, not a prediction or forecast of future outcome. While prognostication is important in deciding to withdraw care, it is not a component in diagnosing brain death.

  11. Brain death in Islamic ethico-legal deliberation: challenges for applied Islamic bioethics.

    Science.gov (United States)

    Padela, Aasim I; Arozullah, Ahsan; Moosa, Ebrahim

    2013-03-01

    Since the 1980s, Islamic scholars and medical experts have used the tools of Islamic law to formulate ethico-legal opinions on brain death. These assessments have varied in their determinations and remain controversial. Some juridical councils such as the Organization of Islamic Conferences' Islamic Fiqh Academy (OIC-IFA) equate brain death with cardiopulmonary death, while others such as the Islamic Organization of Medical Sciences (IOMS) analogize brain death to an intermediate state between life and death. Still other councils have repudiated the notion entirely. Similarly, the ethico-legal assessments are not uniform in their acceptance of brain-stem or whole-brain criteria for death, and consequently their conceptualizations of, brain death. Within the medical literature, and in the statements of Muslim medical professional societies, brain death has been viewed as sanctioned by Islamic law with experts citing the aforementioned rulings. Furthermore, health policies around organ transplantation and end-of-life care within the Muslim world have been crafted with consideration of these representative religious determinations made by transnational, legally-inclusive, and multidisciplinary councils. The determinations of these councils also have bearing upon Muslim clinicians and patients who encounter the challenges of brain death at the bedside. For those searching for 'Islamically-sanctioned' responses that can inform their practice, both the OIC-IFA and IOMS verdicts have palpable gaps in their assessments and remain clinically ambiguous. In this paper we analyze these verdicts from the perspective of applied Islamic bioethics and raise several questions that, if answered by future juridical councils, will better meet the needs of clinicians and bioethicists.

  12. Clinical utility of arterial spin-labeling as a confirmatory test for suspected brain death.

    Science.gov (United States)

    Kang, K M; Yun, T J; Yoon, B-W; Jeon, B S; Choi, S H; Kim, J-H; Kim, J E; Sohn, C-H; Han, M H

    2015-05-01

    Diagnosis of brain death is made on the basis of 3 essential findings: coma, absence of brain stem reflexes, and apnea. Although confirmatory tests are not mandatory in most situations, additional testing may be necessary to declare brain death in patients in whom results of specific components of clinical testing cannot be reliably evaluated. Recently, arterial spin-labeling has been incorporated as part of MR imaging to evaluate cerebral perfusion. Advantages of arterial spin-labeling include being completely noninvasive and providing information about absolute CBF. We retrospectively reviewed arterial spin-labeling findings according to the following modified criteria based on previously established confirmatory tests to determine brain death: 1) extremely decreased perfusion in the whole brain, 2) bright vessel signal intensity around the entry of the carotid artery to the skull, 3) patent external carotid circulation, and 4) "hollow skull sign" in a series of 5 patients. Arterial spin-labeling findings satisfied the criteria for brain death in all patients. Arterial spin-labeling imaging has the potential to be a completely noninvasive confirmatory test to provide additional information to assist in the diagnosis of brain death.

  13. A Thomistic defense of whole-brain death

    OpenAIRE

    Eberl, Jason T.

    2015-01-01

    Michel Accad critiques the currently accepted whole-brain criterion for determining the death of a human being from a Thomistic metaphysical perspective and, in so doing, raises objections to a particular argument defending the whole-brain criterion by Patrick Lee and Germain Grisez. In this paper, I will respond to Accad's critique of the whole-brain criterion and defend its continued validity as a criterion for determining when a human being's death has occurred in accord with Thomistic met...

  14. [Two cases in which the presence of ciliospinal response led to indecisiveness in the evaluation of brain death].

    Science.gov (United States)

    Ikeda, H; Aruga, T; Hayashi, M; Miyake, Y; Sugimoto, K; Mastumoto, K

    1999-02-01

    The ciliospinal reflex was first described by Budge in 1852. This reflex is used as an indicator of brain stem and autonomic nervous system functioning. In the Japanese guideline for determining brain death, the absence of this reflex is considered essential. We reported two cases in which the ciliospinal responses judged to be present resulted in the authors' indecision in determining brain death. They were the cases of a 74-year-old woman who suffered a right putaminal hemorrhage and that of a 28 year-old male with severe head and cervical cord injury. Although brain death was suspected in both cases from its clinical courses, the fact that the ciliospinal reflex was present in each case kept us from declaring that these patients were in the state of brain death. The center of the ciliospinal reflex lies in the first three segments of the thoracic spinal segments and two pathways are involved in this reflex. A noxious stimulation to the face will be registered through the brain stem, but if stimulation is in the neck or upper trunk, it may go directly to the spinal center. Because of the latter pathway to the spinal center, this reflex might remain in patients in whom the brain stem is completely nonfunctioning. Therefore, the presence of this reflex dose not always preclude a state of brain death.

  15. Of wholes and parts: A Thomistic refutation of "Brain Death".

    Science.gov (United States)

    Accad, Michel

    2015-08-01

    I propose a refutation of the two major arguments that support the concept of "brain death" as an ontological equivalent to death of the human organism. I begin with a critique of the notion that a body part, such as the brain, could act as "integrator" of a whole body. I then proceed with a rebuttal of the argument that destruction of a body part essential for rational operations-such as the brain-necessarily entails that the remaining whole is indisposed to accrue a rational soul. Next, I point to the equivocal use of the terms "alive" or "living" as being at the root of conceptual errors about brain death. I appeal to the Thomistic definition of life and to the hylomorphic concept of "virtual presence" to clarify this confusion. Finally, I show how the Thomistic definition of life supports the traditional criterion for the determination of death. Lay summary: By the mid-1960s, medical technology became available that could keep "alive" the bodies of patients who had sustained complete and irreversible brain injury. The concept of "brain death" emerged to describe such states. Physicians, philosophers, and ethicists then proposed that the state of brain death is equivalent to the state of death traditionally identified by the absence of spontaneous pulse and respiration. This article challenges the major philosophical arguments that have been advanced to draw this equivalence.

  16. Hypoxic-ischemic encephalopathy with cystic brain stem necroses and thalamic calcifications in a preterm twin.

    Science.gov (United States)

    Peters, B; Walka, M M; Friedmann, W; Stoltenburg-Didinger, G; Obladen, M

    2000-06-01

    A severe and rare ischemic brain lesion in a preterm twin boy is reported. The boy was born after two weeks of anhydramnios and amnionic infection at 24 weeks of gestation. Following a difficult Caesarean section and prolonged umbilical cord compression he developed prenatal acidosis with an umbilical cord pH of 6.96. At the age of 7 h, heart rate variability narrowed due to severely disturbed brain stem function and the patient developed clinical signs of hypoxic-ischemic encephalopathy. Sonography demonstrated extensive symmetrical brain stem and basal ganglia lesions. After a prolonged comatose and apneic state, death occurred at the age of 25 days. Autopsy confirmed columnar bilateral cavitation of basal ganglia, diencephalon, brain stem and spinal gray matter, as well as focal calcifications in the palladium, thalamus, and brain stem. The findings highly resemble those observed after experimental or clinical cardiac arrest.

  17. The transatlantic divide over brain death determination and the debate.

    Science.gov (United States)

    Wijdicks, Eelco F M

    2012-04-01

    In 1976, the Royal College of Physicians published neurological criteria of death. The memorandum stated that-after preconditions and exclusion criteria were met-the absence of brainstem function, including apnoea testing, would suffice. In the USA, many experts felt that brain death could be only determined by demonstrating death of the entire brain. In the history of further refinement of UK and USA brain death criteria, one particular period stands out that would bring about an apparent transatlantic divide. On 13 October 1980, the British Broadcasting Corporation aired a programme entitled 'Transplants: Are the Donors Really Dead?' Several United States experts not only disagreed with the United Kingdom criteria, but claimed that patients diagnosed with brain death using United Kingdom criteria could recover. The fallout of this television programme was substantial, as indicated by a media frenzy and a 6-month period of heated correspondence within The Lancet and The British Medical Journal. Members of the Parliament questioned the potential long-term effect on the public's trust in organ transplantation. Given the concerns raised, the British Broadcasting Corporation commissioned a second programme, which was broadcast on 19 February 1981 entitled 'A Question of Life or Death: The Brain Death Debate.' Two panels debated the issues on the accuracy of the electroencephalogram and its place, the absolute need for assessing preconditions before an examination, the problems with recognition of toxins and the feasibility of doing a new prospective study in the United Kingdom, which would follow patients' examination assessed with United Kingdom criteria until cardiac standstill. The positions of the United States and United Kingdom remained diametrically opposed to each other. This article revisits this landmark moment and places it in a wider historical context. In the USA, the focus was not on the brainstem, and the definition of brain death became rapidly infused

  18. Embryonic death and the creation of human embryonic stem cells

    OpenAIRE

    Landry, Donald W.; Zucker, Howard A.

    2004-01-01

    The creation of human embryonic stem cells through the destruction of a human embryo pits the value of a potential therapeutic tool against that of an early human life. This contest of values has resulted in a polarized debate that neglects areas of common interest and perspective. We suggest that a common ground for pursuing research on human embryonic stem cells can be found by reconsidering the death of the human embryo and by applying to this research the ethical norms of essential organ ...

  19. Embryonic death and the creation of human embryonic stem cells.

    Science.gov (United States)

    Landry, Donald W; Zucker, Howard A

    2004-11-01

    The creation of human embryonic stem cells through the destruction of a human embryo pits the value of a potential therapeutic tool against that of an early human life. This contest of values has resulted in a polarized debate that neglects areas of common interest and perspective. We suggest that a common ground for pursuing research on human embryonic stem cells can be found by reconsidering the death of the human embryo and by applying to this research the ethical norms of essential organ donation.

  20. Outcome of kidney transplantation between controlled cardiac death and brain death donors: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Ming Yingzi; Shao Mingjie; Tian Tingting; She Xingguo; Liu Hong; Ye Shaojun; Ye Qifa

    2014-01-01

    Background Our goal was to evaluate the outcomes of kidney transplants from controlled cardiac death donors compared with brain death donors by conducting a meta-analysis of cohort studies.Methods The PubMed database and EMBASE were searched from January 1980 to July 2013 to identify studies that met pre-stated inclusion criteria.Reference lists of retrieved articles were also reviewed.Two authors independently extracted information on the designs of the studies,the characteristics of the study participants,and outcome assessments.Results Nine cohort studies involving 84 398 participants were included in this meta-analysis; 3 014 received kidneys from controlled cardiac death donors and 80 684 from brain death donors.Warm ischemia time was significantly longer for the controlled cardiac death donor group.The incidence of delayed graft function was 2.74 times (P <0.001) greater in the controlled cardiac death donor group.The results are in favor of the brain death donor group on short-term patient and graft survival while this difference became nonsignificant at mid-term and long term.Sensitivity analysis yielded similar results.No evidence of publication bias was observed.Conclusion This meta-analysis of retrospective cohort studies suggests that the outcome after controlled cardiac death donors is comparable with that obtained using kidneys from brain death donors.

  1. Diagnosis of brain death: confirmatory tests after clinical test

    Institute of Scientific and Technical Information of China (English)

    Su Yingying; Yang Qinglin; Liu Gang; Zhang Yan; Ye Hong; Gao Daiquan; Zhang Yunzhou

    2014-01-01

    Background The brain death confirmation tests occupy a different position in each country's diagnostic criteria (or guideline); the choices of tests are also different.China brain death criteria include clinical judgment and confirmation tests.This study aimed to confirm the preferred confirmatory test and complementary confirmatory tests.Methods We did a clinical brain death determination on deep coma patients,and then divided them into brain death group and non-brain death group.According to the Chinese standards for determining brain death,both the groups accepted confirmatory tests including electroencephalograph (EEG),somatosensory evoked potentials (SEP),and transcranial Doppler (TCD).The sensitivity,specificity,false positive rate,and false negative rate were calculated to evaluate the accuracy of the confirmatory tests.Results Among the 131 cases of patients,103 patients met the clinical criteria of brain death.Respiratory arrest provocation test was performed on 44 cases and 32 cases (73%) successfully completed and confirmed that they have no spontaneous breathing.Of the three confirmation tests,EEG had the highest completion rate (98%) and good sensitivity (83%) and specificity (97%); TCD had followed completion rate (54%) and not good sensitivity (73%) and specificity (75%); SEP had the lowest completion rate (49%),good sensitivity (100%),and not good specificity (78%).After the combination of SEP or TCD with EEG,the specificity can increase to 100%.Conclusions The completion rate of respiratory arrest provocation test remains a problem in the clinical diagnosis of brain death.If the test cannot be completed,whether to increase a confirmatory test is debatable.SEP had an ideal sensitivity,and the specificity will reach 100% after combining with TCD or EEG.When a confirmed test was uncertain,we suggest increasing another confirmatory test.

  2. Transient brain ischemia: NMDA receptor modulation and delayed neuronal death

    OpenAIRE

    Benquet, Pascal; Gee, Christine E.; Gerber, Urs

    2008-01-01

    Transient global ischemia induces delayed neuronal death in certain cell types and brain regions while sparing cells in other areas. A key process through which oxygen-glucose deprivation triggers cell death is the excessive accumulation of the neurotransmitter glutamate leading to over excitation of neurons. In certain neurons this increase in glutamate will potentiate the NMDA type of glutamate receptor, which can then initiate cell death. This review provides an update of the neurophysiolo...

  3. Intensive care practices in brain death diagnosis and organ donation.

    Science.gov (United States)

    Escudero, D; Valentín, M O; Escalante, J L; Sanmartín, A; Perez-Basterrechea, M; de Gea, J; Martín, M; Velasco, J; Pont, T; Masnou, N; de la Calle, B; Marcelo, B; Lebrón, M; Pérez, J M; Burgos, M; Gimeno, R; Kot, P; Yus, S; Sancho, I; Zabalegui, A; Arroyo, M; Miñambres, E; Elizalde, J; Montejo, J C; Domínguez-Gil, B; Matesanz, R

    2015-10-01

    We conducted a multicentre study of 1844 patients from 42 Spanish intensive care units, and analysed the clinical characteristics of brain death, the use of ancillary testing, and the clinical decisions taken after the diagnosis of brain death. The main cause of brain death was intracerebral haemorrhage (769/1844, 42%), followed by traumatic brain injury (343/1844, 19%) and subarachnoid haemorrhage (257/1844, 14%). The diagnosis of brain death was made rapidly (50% in the first 24 h). Of those patients who went on to die, the Glasgow Coma Scale on admission was ≤ 8/15 in 1146/1261 (91%) of patients with intracerebral haemorrhage, traumatic brain injury or anoxic encephalopathy; the Hunt and Hess Scale was 4-5 in 207/251 (83%) of patients following subarachnoid haemorrhage; and the National Institutes of Health Stroke Scale was ≥ 15 in 114/129 (89%) of patients with strokes. Brain death was diagnosed exclusively by clinical examination in 92/1844 (5%) of cases. Electroencephalography was the most frequently used ancillary test (1303/1752, 70.7%), followed by transcranial Doppler (652/1752, 37%). Organ donation took place in 70% of patients (1291/1844), with medical unsuitability (267/553, 48%) and family refusal (244/553, 13%) the main reasons for loss of potential donors. All life-sustaining measures were withdrawn in 413/553 of non-donors (75%).

  4. Brain death criteria formulated for transplantation purposes: fact or myth?

    Science.gov (United States)

    Pabisiak, Krzysztof

    2016-01-01

    Medical progress has moved the boundaries of life that were set many centuries ago. The development of medical techniques has allowed us to witness cases that were unknown prior to the introduction of reanimation procedures and mechanical ventilation. Towards the end of the 1950s, the term "irreversible coma" was coined, and has evolved into what is currently known as the "brain death" concept. This latter concept, proposed in 1968, is very often referred to as the new definition of death, even in medical circles. What, up until this time, used to be the classic definition of death, namely cessation of circulation and respiration, should now be recognized as the classic criteria for death. Indeed, the new criteria for recognizing death has not resulted in changing the current criteria, but in complementing them. The first part of this paper presents brief descriptions of death in the humanities over the centuries and the impact of progress in medicine on changes in how death is defined today. The second part brings to light the complexity of creating the foundations of the neurological criteria for death. The integration of concepts from two complementary medical fields - neurology and transplantology - is described. Although for some period of time they have been linked together, they may grow independently in the future. The jargon phrase "brain death" is nowadays recognized as synonym of death, but in fact should be considered tantamount to declaring pronouncing a person's death.

  5. Brain stem evoked response audiometry A Review

    OpenAIRE

    Balasubramanian Thiagarajan

    2015-01-01

    Brain stem evoked response audiometry (BERA) is a useful objective assessement of hearing. Major advantage of this procedure is its ability to test even infants in whom conventional audiometry may not be useful. This investigation can be used as a screening test for deafness in high risk infants. Early diagnosis and rehabilitation will reduce disability in these children. This article attempts to review the published literature on this subject. Methadology: Internet search using goog...

  6. CT findings as confirmatory criteria of brain death

    Energy Technology Data Exchange (ETDEWEB)

    Shiogai, Toshiyuki; Takeuchi, Kazuo (Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine)

    1983-12-01

    The absence of cerebral circulation and electrocerebral silence have served as an accurate index of irreversible brain death. It is proposed that computed tomography (CT) findings be evaluated as confirmatory criteria of brain death. To this end, CT evaluation of 14 patients satisfying the conventional criteria of brain death was performed. A CT finding of severe compression or dissappearance of the ventricular system, or so called ''brain tamponade'', was seen in 7 (50 %) of the 14 patients. Enhanced contrast CT, especially dynamic CT, usually distinctly reveals the cerebral vessels whenever the cerebral blood flow is preserved; conversely, the lack of enhanced brain structures, even comparing attenuation values, indicates the absence of cerebral blood flow. In 7 (70 %) of 10 patients, however, there was enhanced contrast of vascular brain structures, especially the circle of Willis, major cerebral arteries, choroid plexuses, and venous sinuses. It is suggested that this result is due to the improvement of demonstrability by CT. The usefulness of CT in the confirmation of brain death lies in visualization of the pathological changes associated with a dead brain, such as ''brain tamponade'', and the lack of enhanced contrast indicating the absence of cerebral blood flow. The latter point is still problematic as angiography revealed an extremely low cerebral blood flow in a few cases of ''dead brain'' patients. It is recommended that cerebral blood flow in brain death be evaluated by dynamic CT scanning and correlated with other methods of cerebral blood flow determination (e.g., intravenous digital subtraction angiography).

  7. Similar liver transplantation survival with selected cardiac death donors and brain death donors

    NARCIS (Netherlands)

    Dubbeld, J.; Hoekstra, H.; Farid, W.; Ringers, J.; Porte, R. J.; Metselaar, H. J.; Baranski, A. G.; Kazemier, G.; van den Bere, A. P.; van Hoek, B.

    2010-01-01

    Background: The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive

  8. A Thomistic defense of whole-brain death.

    Science.gov (United States)

    Eberl, Jason T

    2015-08-01

    Michel Accad critiques the currently accepted whole-brain criterion for determining the death of a human being from a Thomistic metaphysical perspective and, in so doing, raises objections to a particular argument defending the whole-brain criterion by Patrick Lee and Germain Grisez. In this paper, I will respond to Accad's critique of the whole-brain criterion and defend its continued validity as a criterion for determining when a human being's death has occurred in accord with Thomistic metaphysical principles. I will, however, join Accad in criticizing Lee and Grisez's proposed defense of the whole-brain criterion as potentially leading to erroneous conclusions regarding the determination of human death. Lay summary: Catholic physicians and bioethicists currently debate the legally accepted clinical standard for determining when a human being has died-known as the "wholebrain criterion"-which has also been morally affirmed by the Magisterium. This paper responds to physician Michel Accad's critique of the whole-brain criterion based upon St. Thomas Aquinas's metaphysical account of human nature as a union of a rational soul and a material body. I defend the whole-brain criterion from the same Thomistic philosophical perspective, while agreeing with Accad's objection to an alternative Thomistic defense of whole-brain death by philosophers Patrick Lee and Germain Grisez.

  9. Why brain death is considered death and why there should be no confusion.

    Science.gov (United States)

    Burkle, Christopher M; Sharp, Richard R; Wijdicks, Eelco F

    2014-10-14

    Neurologic determination of brain death is a complex assessment that may be misunderstood by nonspecialists and families. Recent guidelines clarify how to proceed with such an examination and are available to physicians, with the time of death in adults and children being determined by the last defining test-the apnea test. This core principle in neurology has been challenged recently in court and resulted in an unprecedented continuation of care in a 13-year-old child declared dead. This review comments on the medical, legal, and ethical quandaries introduced by this case and highlights the major elements of consensus on matters related to brain death that have been forged over 3 decades of sustained medical and societal debate. A clear appreciation by physicians and the public of the diagnostic determination of death following loss of brain function will help to prevent similar conflicts from occurring in the future.

  10. MRI of 'brain death'

    Energy Technology Data Exchange (ETDEWEB)

    Nishino, Shigeki; Itoh, Takahiko; Tuchida, Shohei; Kinugasa, Kazushi; Asari, Shoji; Nishimoto, Akira (Okayama Univ. (Japan). School of Medicine); Sanou, Kazuo

    1990-12-01

    Magnetic resonance imaging (MRI) was undertaken for two patients who suffered from severe cerebrovascular diseases and were clinically brain dead. The MRI system we used was Resona (Yokogawa Medical Systems, superconductive system 0.5 T) and the CT apparatus was Toshiba TCT-300. Initial CT and MRI were undertaken as soon as possible after admission, and repeated sequentially. After diagnosis of brain death, we performed angiography to determine cerebral circulatory arrest, and MRI obtained at the same time was compared with the angiogram and CT. Case 1 was a 77-year-old man who was admitted in an unconscious state. CT and MRI on the second day after hospitalization revealed cerebellar infarction. He was diagnosed as brain dead on day 4. Case 2 was a 35-year-old man. When he was transferred to our hospital, he was in cardiorespiratory arrested. Cardiac resuscitation was successful but no spontaneous respiration appeared. CT and MRI on admission revealed right intracerebral hemorrhage. Angiography revealed cessation of contrast medium in intracranial vessels in both of the patients. We found no 'flow signal void sign' in the bilateral internal carotid and basilar arteries on MRI images in both cases after brain death. MRI, showing us the anatomical changes of the brain, clearly revealed brain herniations, even though only nuclear findings of 'brain tamponade' were seen on CT. But in Case 1, we could not see the infarct lesions in the cerebellum on MR images obtained after brain death. This phenomenon was caused by the whole brain ischemia masking the initial ischemic lesions. We concluded that MRI was useful not only the anatomical display of lesions and brain herniation with high contrast resolution but for obtaining information on cerebral circulation of brain death. (author).

  11. Imaging Findings of Brain Death on 3-Tesla MRI

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Chul Ho [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Hwa Pyung [Dept. of Occupational and Environmental Medicine, CHA Gumi Medical Center, CHA University, Gumi (Korea, Republic of); Park, Jun Beom [Dept. of Radiology, Korean Armed Force Daejeon Hospital, Daejeon (Korea, Republic of); Chang, Hyuk Won; Kim, Easlmaan; Park, Ui Jun; Kim, Hyoung Tae [Keimyung University College of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of); Kim, Eun Hee [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Ku, Jeong Hun [Dept. of Biomedical Engineering, Keimyung University College of Medicine, Daegu (Korea, Republic of)

    2012-09-15

    To demonstrate the usefulness of 3-tesla (3T) magnetic resonance imaging (MRI) including T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), time-of-flight (TOF) magnetic resonance angiography (MRA), T2*-weighted gradient recalled echo (GRE), and susceptibility weighted imaging (SWI) in diagnosing brain death. Magnetic resonance imaging findings for 10 patients with clinically verified brain death (group I) and seven patients with comatose or stuporous mentality who did not meet the clinical criteria of brain death (group II) were retrospectively reviewed. Tonsilar herniation and loss of intraarterial flow signal voids (LIFSV) on T2WI were highly sensitive and specific findings for the diagnosis of brain death (p < 0.001 and < 0.001, respectively). DWI, TOF-MRA, and GRE findings were statistically different between the two groups (p = 0.015, 0.029, and 0.003, respectively). However, cortical high signal intensities in T2WI and SWI findings were not statistically different between the two group (p = 0.412 and 1.0, respectively). T2-weighted imaging, DWI, and MRA using 3T MRI may be useful for diagnosing brain death. However, SWI findings are not specific due to high false positive findings.

  12. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    OpenAIRE

    2011-01-01

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cel...

  13. Pitfalls in brain death diagnosis: a case report.

    Science.gov (United States)

    Ruess, Daniel; Rieger, Bernhard; Goldbrunner, Roland; Schlacke, Hans-Peter

    2013-05-01

    Although there are distinct guidelines in nearly all countries, a reliable secure assessment of brain death in cases with open head injury can be challenging. We present a case of a 32-year-old man with severe head injury after intracranial penetration of a grindstone fragment. As the injury led to destruction of nearly the whole greater wing of the right sphenoid bone and parts of the right orbit, the examination of brainstem reflexes and the confirmation of brain death was unfeasible. On day 2, all clinical criteria of brain death (coma, absence of brainstem reflexes, apnea) were fulfilled. In addition, there was an extinction of brainstem auditory (BAEP) and cerebral (N20) components of median nerve somatosensory evoked potentials, while electroencephalogram (EEG) activity was still present. In the following days, a persisting EEG activity was obtained. Thus, an irreversible loss of whole brain functions could not be proved. As the patient had agreed to organ donation in case of brain death several years ago, ancillary methods to test the cessation of cerebral blood flow were mandatory. However, in this patient these methods turned out either to be doubtful or unavailable. For example, values of transcranial Doppler ultrasonography are not reliable in cases with open head injury. Due to a progressive septic state, time was running out to get the radiopharmaceutical agent for a cerebral scintigraphy (delivery time about 7 days, as the radiopharmaceutical agent was not in stock). Referring to the actual German guidelines, we had no legitimating indication for a cerebral angiography. Finally, the patient died of sepsis. We discuss the widening of the German guidelines in assessing brain death with the fast and low-risk method of cerebral computed tomography-angiography (CTA) to confirm diagnosis of brain death.

  14. Brain death and marginal grafts in liver transplantation.

    Science.gov (United States)

    Jiménez-Castro, M B; Gracia-Sancho, J; Peralta, C

    2015-06-04

    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.

  15. Death Associated Protein Kinases: Molecular Structure and Brain Injury

    OpenAIRE

    Claire Thornton; Carina Mallard; Rajanikant Krishnamurthy; Syam Nair; Henrik Hagberg

    2013-01-01

    Perinatal brain damage underlies an important share of motor and neurodevelopmental disabilities, such as cerebral palsy, cognitive impairment, visual dysfunction and epilepsy. Clinical, epidemiological, and experimental studies have revealed that factors such as inflammation, excitotoxicity and oxidative stress contribute considerably to both white and grey matter injury in the immature brain. A member of the death associated protein kinase (DAPk) family, DAPk1, has been implicated in cerebr...

  16. Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS. Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

  17. Drugs and brain death: drug assay perspectives.

    Science.gov (United States)

    Morris, R G

    1996-08-01

    The ability to make any meaningful interpretation of a drug assay result is very dependent upon a knowledge of the limitations of the method(s) used (sensitivity, specificity etc.), and the concentration that may be measured in plasma and its relationship to CNS effects. We need more information about 'critical' concentrations for each drug and sedation in the setting of the brain-injured patient before meaningful interpretation can be applied to such data. While the above discussion is critical of screen-type assays, the alternative specific assays are not easily provided for, as obviously the resourcing of laboratories to be able to deliver such specialized services for a range of therapeutic drugs, in addition to 'social' drugs or other toxins (e.g. glues, pesticides, solvents, environmental substances etc), becomes an increasingly complex issue in the current economic climate. Hence, the analytical laboratory can offer valuable support to the clinical team however, the interpretation of such results must be assessed in the light of many limitations of such assay methods and not seen as the 'gold standard' for assessment of brain function.

  18. Guideline of procedures 2003 for the gammagraphic study of brain death; Guia de procedimientos 2003 para el estudio gammagrafico de muerte cerebral

    Energy Technology Data Exchange (ETDEWEB)

    Mora R, R.A. [Instituto Nacional de Pediatria, Mexico D.F. (Mexico)

    2003-07-01

    The diagnosis of brain death is a clinical diagnosis that is sometimes made with the help of cerebral perfusion scintigraphy. It is important that all physicians be knowledgeable about the clinical requirements for the diagnosis of brain death, especially the need to establish irreversible cessation of all function of the cerebrum and brain stem. Institutions performing scintigraphy for the evaluation of possible brain death should develop clinical guidelines and procedures for the clinical diagnosis that incorporate both clinical evaluations and the integration of ancillary tests such as perfusion scintigraphy. (Author)

  19. Brain death in ICU patients: Clinical significance of endocrine changes

    Directory of Open Access Journals (Sweden)

    Sukhminder Jit Singh Bajwa

    2014-01-01

    Full Text Available Numerous studies have been carried out among patients admitted in intensive care unit (ICU having primary endocrine pathology, endocrine manifestations of systemic diseases or post-endocrine tissue surgery. However, minimal literary evidence is available highlighting the endocrine changes occurring during brain death in critically ill patients. A precise and timely diagnosis of brain death is required to convey the relatives about the prognosis and also to possibly plan for organ retrieval for transplantation purposes. The diagnosis of this condition as of today remains largely a clinical one. Brain death is associated with a multitude of endocrinological alterations which are yet to be completely unraveled and understood. Evaluating these endocrinological modifications lends us an added vista to add to the existing clinical parameters which might help us to confirm the diagnosis of brain death with a higher degree of precision. Moreover, since the efficacy of hormone replacement therapy to benefit in organ retrieval remains yet unproven, newer diagnostic modalities and research studies are definitely called for to strategize the optimal dosage and duration of such therapies.

  20. Interplay between autophagy and programmed cell death in mammalian neural stem cells

    Directory of Open Access Journals (Sweden)

    Kyung Min Chung

    2013-08-01

    Full Text Available Mammalian neural stem cells (NSCs are of particular interestbecause of their role in brain development and function. Recentfindings suggest the intimate involvement of programmed celldeath (PCD in the turnover of NSCs. However, the underlyingmechanisms of PCD are largely unknown. Although apoptosis isthe best-defined form of PCD, accumulating evidence hasrevealed a wide spectrum of PCD encompassing apoptosis,autophagic cell death (ACD and necrosis. This mini-reviewaims to illustrate a unique regulation of PCD in NSCs. Theresults of our recent studies on autophagic death of adulthippocampal neural stem (HCN cells are also discussed. HCNcell death following insulin withdrawal clearly provides areliable model that can be used to analyze the molecularmechanisms of ACD in the larger context of PCD. Moreresearch efforts are needed to increase our understanding of themolecular basis of NSC turnover under degenerating conditions,such as aging, stress and neurological diseases. Efforts aimed atprotecting and harnessing endogenous NSCs will offer novelopportunities for the development of new therapeutic strategiesfor neuropathologies. [BMB Reports 2013; 46(8: 383-390

  1. Life and death of neurons in the aging brain

    Science.gov (United States)

    Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

  2. Stem Cells and the Origin and Propagation of Brain Tumors

    OpenAIRE

    2008-01-01

    In recent years there has been a flood of interest in the relationship between brain tumors and stem cells. Some investigators have focused on the sensitivity of normal stem cells to transformation, others have described phenotypic or functional similarities between tumor cells and stem cells, and still others have suggested that tumors contain a subpopulation of “cancer stem cells” that is crucial for tumor maintenance or propagation. While all these concepts are interesting and provide insi...

  3. Milrinone in Enterovirus 71 Brain Stem Encephalitis

    Science.gov (United States)

    Wang, Shih-Min

    2016-01-01

    Enterovirus 71 (EV71) was implicated in a widespread outbreak of hand-foot-and-mouth disease (HFMD) across the Asia Pacific area since 1997 and has also been reported sporadically in patients with brain stem encephalitis. Neurogenic shock with pulmonary edema (PE) is a fatal complication of EV71 infection. Among inotropic agents, milrinone is selected as a therapeutic agent for EV71- induced PE due to its immunopathogenesis. Milrinone is a type III phosphodiesterase inhibitor that has both inotropic and vasodilator effects. Its clinical efficacy has been shown by modulating inflammation, reducing sympathetic over-activity, and improving survival in patients with EV71-associated PE. Milrinone exhibits immunoregulatory and anti-inflammatory effects in the management of systemic inflammatory responses in severe EV71 infection. PMID:27065870

  4. Milrinone in Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    SHIH-MIN eWANG

    2016-03-01

    Full Text Available Enterovirus 71 (EV71 was implicated in a widespread outbreak of hand-foot-and-mouth disease (HFMD across the Asia Pacific area since 1997 and has also been reported sporadically in patients with brain stem encephalitis. Neurogenic shock with pulmonary edema (PE is a fatal complication of EV71 infection. Among inotropic agents, milrinone is selected as a therapeutic agent for EV71- induced PE due to its immunopathogenesis. Milrinone is a type III phosphodiesterase inhibitor that has both inotropic and vasodilator effects. Its clinical efficacy has been shown by modulating inflammation, reducing sympathetic over-activity, and improving survival in patients with EV71-associated PE. Milrinone exhibits immunoregulatory and anti-inflammatory effects in the management of systemic inflammatory responses in severe EV71 infection.

  5. Islam, brain death, and transplantation: culture, faith, and jurisprudence.

    Science.gov (United States)

    Arbour, Richard; AlGhamdi, Hanan Mesfer Saad; Peters, Linda

    2012-01-01

    A significant gap exists between availability of organs for transplant and patients with end-stage organ failure for whom organ transplantation is the last treatment option. Reasons for this mismatch include inadequate approach to potential donor families and donor loss as a result of refractory cardiopulmonary instability during and after brainstem herniation. Other reasons include inadequate cultural competence and sensitivity when communicating with potential donor families. Clinicians may not have an understanding of the cultural and religious perspectives of Muslim families of critically ill patients who may be approached about brain death and organ donation. This review analyzes Islamic cultural and religious perspectives on organ donation, transplantation, and brain death, including faith-based directives from Islamic religious authorities, definitions of death in Islam, and communication strategies when discussing brain death and organ donation with Muslim families. Optimal family care and communication are highlighted using case studies and backgrounds illustrating barriers and approaches with Muslim families in the United States and in the Kingdom of Saudi Arabia that can improve cultural competence and family care as well as increase organ availability within the Muslim population and beyond.

  6. Pathological characteristics of liver allografts from donation after brain death followed by cardiac death in pigs.

    Science.gov (United States)

    Ye, Hui; Wang, Dong-Ping; Zhang, Chuan-Zhao; Zhang, Long-Juan; Wang, Hao-Chen; Li, Zhuo-Hui; Chen, Zhen; Zhang, Tao; Cai, Chang-Jie; Ju, Wei-Qiang; Ma, Yi; Guo, Zhi-Yong; He, Xiao-Shun

    2014-10-01

    Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

  7. Gadolinium-enhanced magnetic resonance angiography in brain death

    Science.gov (United States)

    Luchtmann, M.; Beuing, O.; Skalej, M.; Kohl, J.; Serowy, S.; Bernarding, J.; Firsching, R.

    2014-01-01

    Confirmatory tests for the diagnosis of brain death in addition to clinical findings may shorten observation time required in some countries and may add certainty to the diagnosis under specific circumstances. The practicability of Gadolinium-enhanced magnetic resonance angiography to confirm cerebral circulatory arrest was assessed after the diagnosis of brain death in 15 patients using a 1.5 Tesla MRI scanner. In all 15 patients extracranial blood flow distal to the external carotid arteries was undisturbed. In 14 patients no contrast medium was noted within intracerebral vessels above the proximal level of the intracerebral arteries. In one patient more distal segments of the anterior and middle cerebral arteries (A3 and M3) were filled with contrast medium. Gadolinium-enhanced MRA may be considered conclusive evidence of cerebral circulatory arrest, when major intracranial vessels fail to fill with contrast medium while extracranial vessels show normal blood flow.

  8. [Transient brain ischemia: NMDA receptor modulation and delayed neuronal death].

    Science.gov (United States)

    Benquet, Pascal; Gee, Christine E; Gerber, Urs

    2008-02-01

    Transient global ischemia induces delayed neuronal death in certain cell types and brain regions while sparing cells in other areas. A key process through which oxygen-glucose deprivation triggers cell death is the excessive accumulation of the neurotransmitter glutamate leading to over excitation of neurons. In certain neurons this increase in glutamate will potentiate the NMDA type of glutamate receptor, which can then initiate cell death. This review provides an update of the neurophysiological, cellular and molecular mechanisms inducing post-ischemic plasticity of NMDA receptors, focusing on the sensitive CA1 pyramidal neurons in the hippocampus as compared to the relatively resistant neighboring CA3 neurons. Both a change in the equilibrium between protein tyrosine kinases/phosphatases and an increased density of surface NMDA receptors in response to ischemia may explain the selective vulnerability of specific cell types. Implications for the treatment of stroke and reasons for the failures of human clinical trials utilizing NMDA receptor antagonists are also discussed.

  9. An empirical EEG analysis in brain death diagnosis for adults.

    Science.gov (United States)

    Chen, Zhe; Cao, Jianting; Cao, Yang; Zhang, Yue; Gu, Fanji; Zhu, Guoxian; Hong, Zhen; Wang, Bin; Cichocki, Andrzej

    2008-09-01

    Electroencephalogram (EEG) is often used in the confirmatory test for brain death diagnosis in clinical practice. Because EEG recording and monitoring is relatively safe for the patients in deep coma, it is believed to be valuable for either reducing the risk of brain death diagnosis (while comparing other tests such as the apnea) or preventing mistaken diagnosis. The objective of this paper is to study several statistical methods for quantitative EEG analysis in order to help bedside or ambulatory monitoring or diagnosis. We apply signal processing and quantitative statistical analysis for the EEG recordings of 32 adult patients. For EEG signal processing, independent component analysis (ICA) was applied to separate the independent source components, followed by Fourier and time-frequency analysis. For quantitative EEG analysis, we apply several statistical complexity measures to the EEG signals and evaluate the differences between two groups of patients: the subjects in deep coma, and the subjects who were categorized as brain death. We report statistically significant differences of quantitative statistics with real-life EEG recordings in such a clinical study, and we also present interpretation and discussions on the preliminary experimental results.

  10. Death Associated Protein Kinases: Molecular Structure and Brain Injury

    Directory of Open Access Journals (Sweden)

    Claire Thornton

    2013-07-01

    Full Text Available Perinatal brain damage underlies an important share of motor and neurodevelopmental disabilities, such as cerebral palsy, cognitive impairment, visual dysfunction and epilepsy. Clinical, epidemiological, and experimental studies have revealed that factors such as inflammation, excitotoxicity and oxidative stress contribute considerably to both white and grey matter injury in the immature brain. A member of the death associated protein kinase (DAPk family, DAPk1, has been implicated in cerebral ischemic damage, whereby DAPk1 potentiates NMDA receptor-mediated excitotoxicity through interaction with the NR2BR subunit. DAPk1 also mediate a range of activities from autophagy, membrane blebbing and DNA fragmentation ultimately leading to cell death. DAPk mRNA levels are particularly highly expressed in the developing brain and thus, we hypothesize that DAPk1 may play a role in perinatal brain injury. In addition to reviewing current knowledge, we present new aspects of the molecular structure of DAPk domains, and relate these findings to interacting partners of DAPk1, DAPk-regulation in NMDA-induced cerebral injury and novel approaches to blocking the injurious effects of DAPk1.

  11. Death associated protein kinases: molecular structure and brain injury.

    Science.gov (United States)

    Nair, Syam; Hagberg, Henrik; Krishnamurthy, Rajanikant; Thornton, Claire; Mallard, Carina

    2013-07-04

    Perinatal brain damage underlies an important share of motor and neurodevelopmental disabilities, such as cerebral palsy, cognitive impairment, visual dysfunction and epilepsy. Clinical, epidemiological, and experimental studies have revealed that factors such as inflammation, excitotoxicity and oxidative stress contribute considerably to both white and grey matter injury in the immature brain. A member of the death associated protein kinase (DAPk) family, DAPk1, has been implicated in cerebral ischemic damage, whereby DAPk1 potentiates NMDA receptor-mediated excitotoxicity through interaction with the NR2BR subunit. DAPk1 also mediate a range of activities from autophagy, membrane blebbing and DNA fragmentation ultimately leading to cell death. DAPk mRNA levels are particularly highly expressed in the developing brain and thus, we hypothesize that DAPk1 may play a role in perinatal brain injury. In addition to reviewing current knowledge, we present new aspects of the molecular structure of DAPk domains, and relate these findings to interacting partners of DAPk1, DAPk-regulation in NMDA-induced cerebral injury and novel approaches to blocking the injurious effects of DAPk1.

  12. Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ji Hye [Dept. of Radiology, Kyung Hee University College of Medicine, Seoul (Korea, Republic of); Choi, Woo Suk; Kim, Eui Jong [Dept. of Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Yoon, Sung Sang; Heo, Sung Hyuk [Dept. of Neurology, Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2012-01-15

    Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

  13. Brain death and management of a potential organ donor in the intensive care unit.

    Science.gov (United States)

    Youn, Teddy S; Greer, David M

    2014-10-01

    The concept of brain death developed with the advent of mechanical ventilation, and guidelines for determining brain death have been refined over time. Organ donation after brain death is a common source of transplant organs in Western countries. Early identification and notification of organ procurement organizations are essential. Management of potential organ donors must take into consideration specific pathophysiologic changes for medical optimization. Future aims in intensive and neurocritical care medicine must include reducing practice variability in the operational guidelines for brain death determination, as well as improving communication with families about the process of determining brain death.

  14. Training stem cells for treatment of malignant brain tumors

    Institute of Scientific and Technical Information of China (English)

    Shengwen; Calvin; Li; Mustafa; H; Kabeer; Long; T; Vu; Vic; Keschrumrus; Hong; Zhen; Yin; Brent; A; Dethlefs; Jiang; F; Zhong; John; H; Weiss; William; G; Loudon

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for pa-tients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution(i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

  15. Transcranial amelioration of inflammation and cell death after brain injury

    Science.gov (United States)

    Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.

    2014-01-01

    Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.

  16. The preventive effects of neural stem cells and mesenchymal stem cells intra-ventricular injection on brain stroke in rats

    Directory of Open Access Journals (Sweden)

    Seyed Mojtaba Hosseini

    2015-01-01

    Full Text Available Introduction: Stroke is one of the most important causes of disability in developed countries and, unfortunately, there is no effective treatment for this major problem of central nervous system (CNS; cell therapy may be helpful to recover this disease. In some conditions such as cardiac surgeries and neurosurgeries, there are some possibilities of happening brain stroke. Inflammation of CNS plays an important role in stroke pathogenesis, in addition, apoptosis and neural death could be the other reasons of poor neurological out come after stroke. In this study, we examined the preventive effects of the neural stem cells (NSCs and mesenchymal stem cells (MSCs intra-ventricular injected on stroke in rats. Aim: The aim of this study was to investigate the preventive effects of neural and MSCs for stroke in rats. Materials and Methods: The MSCs were isolated by flashing the femurs and tibias of the male rats with appropriate media. The NSCs were isolated from rat embryo ganglion eminence and they cultured NSCs media till the neurospheres formed. Both NSCs and MSCs were labeled with PKH26-GL. One day before stroke, the cells were injected into lateral ventricle stereotactically. Results: During following for 28 days, the neurological scores indicated that there are better recoveries in the groups received stem cells and they had less lesion volume in their brain measured by hematoxylin and eosin staining. Furthermore, the activities of caspase-3 were lower in the stem cell received groups than control group and the florescent microscopy images showed that the stem cells migrated to various zones of the brains. Conclusion: Both NSCs and MSCs are capable of protecting the CNS against ischemia and they may be good ways to prevent brain stroke consequences situations.

  17. [The German Ethics Council and the Brain Death--Some Clinical Remarks].

    Science.gov (United States)

    Mindach, M

    2015-08-01

    In February 2015, the German Ethics Council released a statement on brain death and organ removal. The Council has decided to adhere to the criterion of brain death as a condition for organ removal, and the majority of the Council holds the view of brain death as the criterion of death. The German medical associations have welcomed this statement, but there is room for further discussion of some aspects of this statement from a clinical point of view.

  18. Brain Death and Human Organismal Integration: A Symposium on the Definition of Death.

    Science.gov (United States)

    Moschella, Melissa

    2016-06-01

    Does the ability of some brain dead bodies to maintain homeostasis with the help of artificial life support actually imply that those bodies are living human organisms? Or might it be possible that a brain dead body on life support is a mere collection of still-living cells, organs and tissues which can coordinate with one another, but which lack the genuine integration that is the hallmark of a unified human organism as a whole? To foster further study of these difficult and timely questions, a Symposium on the Definition of Death was held at The Catholic University of America in June 2014. The Symposium brought together scholars from a variety of disciplines-law, medicine, biology, philosophy and theology-who all share a commitment to the dead donor rule and to a biological definition of death, but who have differing opinions regarding the validity of neurological criteria for human death. The papers found in this special issue are among the fruits of this Symposium.

  19. Mesenchymal Stem Cell Transplantation Attenuates Brain Injury After Neonatal Stroke

    NARCIS (Netherlands)

    van Velthoven, Cindy T. J.; Sheldon, R. Ann; Kavelaars, Annemieke; Derugin, Nikita; Vexler, Zinaida S.; Willemen, Hanneke L. D. M.; Maas, Mirjam; Heijnen, Cobi J.; Ferriero, Donna M.

    2013-01-01

    Background and Purpose-Brain injury caused by stroke is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. Mesenchymal stem cells (MSC) have been shown to improve outcome after neonatal hypoxic-ischemic brain injury mainly by secretion of growth factors stimulati

  20. Apnoea testing to confirm brain death in clinical practice.

    Science.gov (United States)

    van Donselaar, C A; Meerwaldt, J D; van Gijn, J

    1986-01-01

    In six patients an apnoea test was carried out to confirm brain death according to a protocol recommended in the USA. After ten minutes' apnoea the pCO2 did not reach the target value of 7.98 kPa (60 mm Hg) in any of these patients. This was caused by the low initial value and the slow increase of the pCO2. Moreover, we could not confirm the belief that the necessary duration of the apnoea test can be predicted by assuming a rise of the pCO2 of 0.33 kPa (2.5 mm Hg) per minute. PMID:3093640

  1. Apnoea testing to confirm brain death in clinical practice.

    OpenAIRE

    van Donselaar, C. A.; Meerwaldt, J D; van Gijn, J

    1986-01-01

    In six patients an apnoea test was carried out to confirm brain death according to a protocol recommended in the USA. After ten minutes' apnoea the pCO2 did not reach the target value of 7.98 kPa (60 mm Hg) in any of these patients. This was caused by the low initial value and the slow increase of the pCO2. Moreover, we could not confirm the belief that the necessary duration of the apnoea test can be predicted by assuming a rise of the pCO2 of 0.33 kPa (2.5 mm Hg) per minute.

  2. Apnoea testing to confirm brain death in clinical practice.

    Science.gov (United States)

    van Donselaar, C A; Meerwaldt, J D; van Gijn, J

    1986-09-01

    In six patients an apnoea test was carried out to confirm brain death according to a protocol recommended in the USA. After ten minutes' apnoea the pCO2 did not reach the target value of 7.98 kPa (60 mm Hg) in any of these patients. This was caused by the low initial value and the slow increase of the pCO2. Moreover, we could not confirm the belief that the necessary duration of the apnoea test can be predicted by assuming a rise of the pCO2 of 0.33 kPa (2.5 mm Hg) per minute.

  3. Brain stem hypoplasia associated with Cri-du-Chat syndrome.

    Science.gov (United States)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  4. Brain stem hypoplasia associated with Cri-du-Chat syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu [Dept. of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

    2013-12-15

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  5. Considering ethical dilemmas related to brain death in newborns

    Directory of Open Access Journals (Sweden)

    Ilias Chatziioannidis

    2014-01-01

    Full Text Available Brain death (BD, as the irreversible and permanent loss of cerebral and brainstem function, is relatively uncommon among newborns who need life support. It is considered the result of an acute and irreversible central nervous system insult. Asphyxia, severe intracranial hemorrhage and infection are the most common causes of  BD in children. BD diagnosis is usually based on clinical criteria. Dilemmas about life prolonging treatment for severely compromised infants – as brain dead infants are – has become challenging since neonatal intensive care unit (NICU care has developed, quality of life and resource issues are nowadays continuously underlined. Caring for premature babies is expensive and costs have risen especially since an increased number of infants with handicaps survives. Intensivists’ main duty is first to save lives and then to interrupt treatment in certain conditions like detrimental brain damage. The objective of this article is to present ethical decisions regarding brain dead newborns in order to balance between organ donation necessities and withholding/withdrawing treatment, with respect to the important role of infants’ parents in the process.

  6. Opinions on the Legitimacy of Brain Death Among Sunni and Shi'a Scholars.

    Science.gov (United States)

    Miller, Andrew C

    2016-04-01

    The concept of brain death poses a great challenge to clinicians who may be required to bridge the interface of culture, religion, law, and medicine. This review discusses and applies Islamic jurisprudence to the question of whether brain death is accepted as true death under Islamic law. Among the five sources of Islamic law, the Qur'an and Sunnah do not directly address brain death. Scholarly consensus (Ijmā') does not exist, and Qiya does not apply. When applying Ijtihad, the identified collection of non-binding fatwā offer conflicting results. Debate continues as to the validity of brain-death criteria within Islamic circles.

  7. Are there fetal stem cells in the maternal brain?

    Institute of Scientific and Technical Information of China (English)

    Osman Demirhan; Necmi (C)ekin; Deniz Ta(s)temir; Erdal Tun(c); Ali irfan Güzel; Demet Meral; Bülent Demirbek

    2013-01-01

    Fetal cells can enter maternal blood during pregnancy but whether they can also cross the blood-brain barrier to enter the maternal brain remains poorly understood. Previous results suggest that fetal cells are summoned to repair damage to the mother's brain. If this is confirmed, it would open up new and safer avenues of treatment for brain damage caused by strokes and neural diseases. In this study, we aimed to investigate whether a baby's stem cells can enter the maternal brain during pregnancy. Deceased patients who had at least one male offspring and no history of abortion and blood transfusion were included in this study. DNA was extracted from brain tissue samples of deceased women using standard phenol-chloroform extraction and ethanol precipitation methods. Genomic DNA was screened by quantitative fluorescent-polymerase chain reaction amplification together with short tandem repeat markers specific to the Y chromosome, and 13, 18, 21 and X. Any foreign DNA residues that could be used to interpret the presence of fetal stem cells in the maternal brain were monitored. Results indicated that fetal stem cells can not cross the blood-brain barrier to enter the maternal brain.

  8. Hypothalamic-Pituitary Function in Brain Death: A Review.

    Science.gov (United States)

    Nair-Collins, Michael; Northrup, Jesse; Olcese, James

    2016-01-01

    The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord.

  9. EEG guidelines in the diagnosis of brain death.

    Science.gov (United States)

    Szurhaj, W; Lamblin, M-D; Kaminska, A; Sediri, H

    2015-03-01

    In France, for the determination and diagnostic validation of brain death the law requires either two EEG recordings separated by a 4-hour observation period, both showing electrocerebral inactivity; or cerebral angiography examination. Since EEG is available in most hospitals and clinics, it is often used in this indication, at the patient's bedside, especially in the context of organ donation. However, very precise methodology must be followed. The last French guidelines date back to 1989, before the development of digital EEG recording. We present the new guidelines from the Société de Neurophysiologie Clinique de Langue Française. Electrocerebral inactivity may be confirmed when a 30-minute good quality EEG recording shows complete electrocerebral silence, defined as no cerebral activity greater than 2 uV, having first ruled out the possible influence of sedative drugs, metabolic disorders or hypothermia. In the presence of sedative drugs, CT brain angiography will be the gold standard test for this diagnosis. In the newborn, the utmost caution is indicated since electrocerebral inactivity can be observed in the absence of cerebral death. In the infant, the criterion for the observation period to be respected between both EEG recordings needs to be more clearly refined.

  10. Signal Transduction Pathways Involved in Brain Death-Induced Renal Injury

    NARCIS (Netherlands)

    Bouma, H. R.; Ploeg, R. J.; Schuurs, T. A.

    2009-01-01

    Kidneys derived from brain death organ donors show an inferior survival when compared to kidneys derived from living donors. Brain death is known to induce organ injury by evoking an inflammatory response in the donor. Neuronal injury triggers an inflammatory response in the brain, leading to endoth

  11. Drosophila neural stem cells in brain development and tumor formation.

    Science.gov (United States)

    Jiang, Yanrui; Reichert, Heinrich

    2014-01-01

    Neuroblasts, the neural stem cells in Drosophila, generate the complex neural structure of the central nervous system. Significant progress has been made in understanding the mechanisms regulating the self-renewal, proliferation, and differentiation in Drosophila neuroblast lineages. Deregulation of these mechanisms can lead to severe developmental defects and the formation of malignant brain tumors. Here, the authors review the molecular genetics of Drosophila neuroblasts and discuss some recent advances in stem cell and cancer biology using this model system.

  12. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  13. Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.

    Science.gov (United States)

    Kelpke, Stacey S; Chen, Bo; Bradley, Kelley M; Teng, Xinjun; Chumley, Phillip; Brandon, Angela; Yancey, Brett; Moore, Brandon; Head, Hughston; Viera, Liliana; Thompson, John A; Crossman, David K; Bray, Molly S; Eckhoff, Devin E; Agarwal, Anupam; Patel, Rakesh P

    2012-08-01

    Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.

  14. Human Brain Stem Structures Respond Differentially to Noxious Heat

    Directory of Open Access Journals (Sweden)

    Alexander eRitter

    2013-09-01

    Full Text Available Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH with noxious heat led to activation in different columns of the midbrain periaqueductal grey (PAG. The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by fMRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM. In a second experiment we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e. the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.

  15. Improving uniformity in brain death determination policies over time

    Science.gov (United States)

    Wang, Hilary H.; Varelas, Panayiotis N.; Henderson, Galen V.; Wijdicks, Eelco F.M.

    2017-01-01

    Objective: To demonstrate that progress has been made in unifying brain death determination guidelines in the last decade by directly comparing the policies of the US News and World Report's top 50 ranked neurologic institutions from 2006 and 2015. Methods: We solicited official hospital guidelines in 2015 from these top 50 institutions, generated summary statistics of their criteria as benchmarked against the American Academy of Neurology Practice Parameters (AANPP) and the comparison 2006 cohort in 5 key categories, and statistically compared the 2 cohorts' compliance with the AANPP. Results: From 2008 to 2015, hospital policies exhibited significant improvement (p = 0.005) in compliance with official guidelines, particularly with respect to criteria related to apnea testing (p = 0.009) and appropriate ancillary testing (p = 0.0006). However, variability remains in other portions of the policies, both those with specific recommendation from the AANPP (e.g., specifics for ancillary tests) and those without firm guidance (e.g., the level of involvement of neurologists, neurosurgeons, or physicians with education/training specific to brain death in the determination process). Conclusions: While the 2010 AANPP update seems to be concordant with progress in achieving greater uniformity in guidelines at the top 50 neurologic institutions, more needs to be done. Whether further interventions come as grassroots initiatives that leverage technological advances in promoting adoption of new guidelines or as top-down regulatory rulings to mandate speedier approval processes, this study shows that solely relying on voluntary updates to professional society guidelines is not enough. PMID:28077490

  16. Brain death is associated with endoplasmic reticulum stress and apoptosis in rat liver.

    Science.gov (United States)

    Cao, S; Wang, T; Yan, B; Lu, Y; Zhao, Y; Zhang, S

    2014-12-01

    Cell death pathways initiated by stress on the endoplasmic reticulum (ER) have been implicated in a variety of common diseases, such as ischemia/reperfusion injury, diabetes, heart disease, and neurodegenerative disorders. However, the contribution of ER stress to apoptosis and liver injury after brain death is not known. In the present study, we found that brain death induces a variety of signature ER stress markers, including ER stress-specific X box-binding protein 1 and up-regulation of glucose-regulated protein 78. Furthermore, brain death causes up-regulation of C/EBP homologous protein and caspase-12. Consistent with this, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling assay and transmission electron microscopy confirmed apoptosis in the liver after brain death. Taken together, the present study provides strong evidence supporting the presence and importance of ER stress and response in mediating brain death-induced apoptosis and liver injury.

  17. Brain death determination in Israel: the first two years experience following changes to the brain death law-opportunities and challenges.

    Science.gov (United States)

    Cohen, J; Ashkenazi, T; Katvan, E; Singer, P

    2012-09-01

    To increase support for the concept of brain death, changes accommodating requirements of the religious authorities were made to the Brain Death Act in Israel. These included (1) considering patient wishes regarding brain death determination (BDD); (2) mandatory performance of apnea and ancillary testing; (3) establishment of an accreditation committee and (4) requirement for physician training courses. We describe the first 2 years experience following implementation (2010-2011). During 2010, the number of BDD decreased from 21.9/million population (during the years 2007-2009) to 16.0 (p brain death testing (27 cases), inability to perform apnea testing (7) and logistic problems related to ancillary testing (26 cases). The number of physicians available to declare brain death also decreased (210 vs. 102). During 2011, BDDs increased to 20.5/million following the introduction of radionuclide angiography as an ancillary test; other reasons for nondetermination persisted (family resistance 26 cases, inability to perform apnea testing 10 cases). Instead of increasing opportunities, many obstacles were encountered following the changes to the Brain Death Act. Although some of these challenges have been met, longer term follow-up is required to assess their complete impact.

  18. Syrinx of the Spinal Cord and Brain Stem

    Science.gov (United States)

    ... Prompt Healthier Eating Scientists Working on Solar-Powered Prosthetic Limbs Health Highlights: March 23, 2017 Fruit Juice for Kids: A Serving a Day OK ALL NEWS > Resources ... may extend downward to affect the entire cord. Syrinxes that extend into or begin in the lower part of the brain stem may compress pathways ...

  19. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...

  20. How important is the duration of the brain death period for the outcome in kidney transplantation?

    NARCIS (Netherlands)

    Nijboer, Willemijn N.; Moers, Cyril; Leuvenink, Henri G. D.; Ploeg, Rutger J.

    2011-01-01

    P>In kidney transplantation, graft survival using grafts from donation after brain death (DBD) donors is inferior to results after living donation. However, little is known about the effect of the duration of brain death (BDdur) on outcome after transplantation. This is a retrospective Organ Procure

  1. Growth hormone (GH), brain development and neural stem cells.

    Science.gov (United States)

    Waters, M J; Blackmore, D G

    2011-12-01

    A range of observations support a role for GH in development and function of the brain. These include altered brain structure in GH receptor null mice, and impaired cognition in GH deficient rodents and in a subgroup of GH receptor defective patients (Laron dwarfs). GH has been shown to alter neurogenesis, myelin synthesis and dendritic branching, and both the GH receptor and GH itself are expressed widely in the brain. We have found a population of neural stem cells which are activated by GH infusion, and which give rise to neurons in mice. These stem cells are activated by voluntary exercise in a GH-dependent manner. Given the findings that local synthesis of GH occurs in the hippocampus in response to a memory task, and that GH replacement improves memory and cognition in rodents and humans, these new observations warrant a reappraisal of the clinical importance of GH replacement in GH deficient states.

  2. "Brain Death" and dead donor rule. Discussion and proposals on the thesis of Truog.

    Science.gov (United States)

    Bruzzone, Paolo

    2015-01-01

    The introduction in 1968 by the "ad hoc" Harvard committee of the concept of "Brain Death" gave birth to the worldwide diffusion of organ transplantation. Recently "Total Brain Failure" has been proposed as preferred term, instead of "Brain Death", by the President's Council on Bioethics. The concepts of "brain death" and of "dead donor rule" remain the ethical and moral support of organ transplantation. However both criteria has been questioned , either separately or all together , by many authors and particularly by Dr. Robert D. Truog.

  3. A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature.

    Science.gov (United States)

    Ravikumar, Sandhya; Poysophon, Poysophon; Poblete, Roy; Kim-Tenser, May

    2016-01-01

    We describe a case report of fulminant Guillain-Barré syndrome (GBS) mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy, a subtype of GBS, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler (TCD) ultrasound showed appropriate blood flow to the brain. GBS rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and TCDs when uncertainty exists about the reliability of the clinical exam.

  4. Extracorporeal Membrane Oxygenation for the Support of a Potential Organ Donor with a Fatal Brain Injury before Brain Death Determination

    Directory of Open Access Journals (Sweden)

    Sung Wook Chang

    2016-05-01

    Full Text Available The shortage of available organ donors is a significant problem and various efforts have been made to avoid the loss of organ donors. Among these, extracorporeal membrane oxygenation (ECMO has been introduced to help support and manage potential donors. Many traumatic brain injury patients have healthy organs that might be eligible for donation for transplantation. However, the condition of a donor with a fatal brain injury may rapidly deteriorate prior to brain death determination; this frequently results in the loss of eligible donors. Here, we report the use of venoarterial ECMO to support a potential donor with a fatal brain injury before brain death determination, and thereby preserve donor organs. The patient successfully donated his liver and kidneys after brain death determination.

  5. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  6. Mesenchymal Stem Cells in the Treatment of Traumatic Brain Injury

    Science.gov (United States)

    Hasan, Anwarul; Deeb, George; Rahal, Rahaf; Atwi, Khairallah; Mondello, Stefania; Marei, Hany Elsayed; Gali, Amr; Sleiman, Eliana

    2017-01-01

    Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. The primary insult to the brain initiates secondary injury cascades consisting of multiple complex biochemical responses of the brain that significantly influence the overall severity of the brain damage and clinical sequelae. The use of mesenchymal stem cells (MSCs) offers huge potential for application in the treatment of TBI. MSCs have immunosuppressive properties that reduce inflammation in injured tissue. As such, they could be used to modulate the secondary mechanisms of injury and halt the progression of the secondary insult in the brain after injury. Particularly, MSCs are capable of secreting growth factors that facilitate the regrowth of neurons in the brain. The relative abundance of harvest sources of MSCs also makes them particularly appealing. Recently, numerous studies have investigated the effects of infusion of MSCs into animal models of TBI. The results have shown significant improvement in the motor function of the damaged brain tissues. In this review, we summarize the recent advances in the application of MSCs in the treatment of TBI. The review starts with a brief introduction of the pathophysiology of TBI, followed by the biology of MSCs, and the application of MSCs in TBI treatment. The challenges associated with the application of MSCs in the treatment of TBI and strategies to address those challenges in the future have also been discussed.

  7. Brain death and organ transplant legislation:analysis of 969 respondents by classroom questionnaire

    Institute of Scientific and Technical Information of China (English)

    Ru-Liang Song; Xiao-Hua Cui; Zhan Gao; Shao-Lin Deng; You-Ping Li

    2009-01-01

    BACKGROUND: China has the largest potential market for organ transplants in the world, but it has not yet established brain death and organ transplant laws. We aimed to investigate the attitudes and suggestions of doctors, pharmacists, and civil servants concerning brain death, organ transplantation, and their respective legislation. METHODS: A questionnaire with 10 sections and 44 questions was designed and distributed. The effective questionnaire data were then recorded and checked for descriptive analysis. RESULTS: In 1400 questionnaires distributed, 1063 were responded and 969 of them were valid and analyzed. The respondents showed an incomplete understanding of brain death and organ transplantation laws. Seventy-four percent of the respondents recognized and accepted the standard of brain death. They agreed that legislation should be involved in the removal of organs for transplantation, the future use of organs, and insurance and compensation for the donor for possible health risks induced by organ removal. Of the 969 respondents, 92%considered it necessary to have legislation in brain death and organ transplantation, and 61% thought that it is time to legislate. CONCLUSIONS: Legislation for brain death and organ transplantation is urgent and timely in China. The laws must include the respective rights and obligations of patients, close relatives, and medical institutions. Educating the public about brain death and organ transplantation should also be encouraged in a variety of ways.

  8. Brain stem auditory evoked responses in chronic alcoholics.

    OpenAIRE

    Chan, Y W; McLeod, J G; Tuck, R R; Feary, P A

    1985-01-01

    Brain stem auditory evoked responses (BAERs) were performed on 25 alcoholic patients with Wernicke-Korsakoff syndrome, 56 alcoholic patients without Wernicke-Korsakoff syndrome, 24 of whom had cerebellar ataxia, and 37 control subjects. Abnormal BAERs were found in 48% of patients with Wernicke-Korsakoff syndrome, in 25% of alcoholic patients without Wernicke-Korsakoff syndrome but with cerebellar ataxia, and in 13% of alcoholic patients without Wernicke-Korsakoff syndrome or ataxia. The mean...

  9. Bioenergetics failure and oxidative stress in brain stem mediates cardiovascular collapse associated with fatal methamphetamine intoxication.

    Directory of Open Access Journals (Sweden)

    Faith C H Li

    Full Text Available BACKGROUND: Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH, the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM, which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH. METHODOLOGY/PRINCIPAL FINDINGS: Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemical events were reversed on microinjection into RVLM of a mobile electron carrier in the mitochondrial respiratory chain, coenzyme Q10; a mitochondria-targeted antioxidant and superoxide anion scavenger, Mito-TEMPO; or an oxidative stress-induced necrotic cell death inhibitor, IM-54. CONCLUSION: We conclude that sustained anoxia and cessation of local blood flow

  10. Stem cell-paved biobridges facilitate stem transplant and host brain cell interactions for stroke therapy.

    Science.gov (United States)

    Duncan, Kelsey; Gonzales-Portillo, Gabriel S; Acosta, Sandra A; Kaneko, Yuji; Borlongan, Cesar V; Tajiri, Naoki

    2015-10-14

    Distinguished by an infarct core encased within a penumbra, stroke remains a primary source of mortality within the United States. While our scientific knowledge regarding the pathology of stroke continues to improve, clinical treatment options for patients suffering from stroke are extremely limited. Tissue plasminogen activator (tPA) remains the sole FDA-approved drug proven to be helpful following stroke. However, due to the need to administer the drug within 4.5h of stroke onset its usefulness is constrained to less than 5% of all patients suffering from ischemic stroke. One experimental therapy for the treatment of stroke involves the utilization of stem cells. Stem cell transplantation has been linked to therapeutic benefit by means of cell replacement and release of growth factors; however the precise means by which this is accomplished has not yet been clearly delineated. Using a traumatic brain injury model, we recently demonstrated the ability of transplanted mesenchymal stromal cells (MSCs) to form a biobridge connecting the area of injury to the neurogenic niche within the brain. We hypothesize that MSCs may also have the capacity to create a similar biobridge following stroke; thereby forming a conduit between the neurogenic niche and the stroke core and peri-infarct area. We propose that this biobridge could assist and promote interaction of host brain cells with transplanted stem cells and offer more opportunities to enhance the effectiveness of stem cell therapy in stroke. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

  11. Danish ethics council rejects brain death as the criterion of death -- commentary 2: return to Elsinore.

    Science.gov (United States)

    Pallis, Christopher

    1990-03-01

    No discussion of when an individual is dead is meaningful in the absence of a definition of death. If human death is defined as the irreversible loss of the capacity for consciousness combined with the irreversible loss of the capacity to breathe spontaneously (and hence to maintain a spontaneous heart beat) the death of the brainstem will be seen to be the necessary and sufficient condition for the death of the individual. Such a definition of death is not something radically new. It is merely the reformulation -- in the language of the neurophysiologist -- of much older concepts such as the 'departure of the (conscious) soul from the body' and the 'loss of the breath of life'. All death -- in this perspective -- is, and always has been, brainstem death....

  12. The Case for Reasonable Accommodation of Conscientious Objections to Declarations of Brain Death.

    Science.gov (United States)

    Johnson, L Syd M

    2016-03-01

    Since its inception in 1968, the concept of whole-brain death has been contentious, and four decades on, controversy concerning the validity and coherence of whole-brain death continues unabated. Although whole-brain death is legally recognized and medically entrenched in the United States and elsewhere, there is reasonable disagreement among physicians, philosophers, and the public concerning whether brain death is really equivalent to death as it has been traditionally understood. A handful of states have acknowledged this plurality of viewpoints and enacted "conscience clauses" that require "reasonable accommodation" of religious and moral objections to the determination of death by neurological criteria. This paper argues for the universal adoption of "reasonable accommodation" policies using the New Jersey statute as a model, in light of both the ongoing controversy and the recent case of Jahi McMath, a child whose family raised religious objections to a declaration of brain death. Public policies that accommodate reasonable, divergent viewpoints concerning death provide a practical and compassionate way to resolve those conflicts that are the most urgent, painful, and difficult to reconcile.

  13. Use of Transcranial Doppler Ultrasound for Diagnosis of Brain Death in Patients with Severe Cerebral Injury.

    Science.gov (United States)

    Li, Yuequn; Liu, Shangwei; Xun, Fangfang; Liu, Zhan; Huang, Xiuying

    2016-06-06

    BACKGROUND The aim of this study was to investigate the use of transcranial Doppler (TCD) for diagnosis of brain death in patients with severe cerebral injury. MATERIAL AND METHODS This retrospective study enrolled 42 patients based on inclusion and exclusion criteria. All patients were divided into either the brain death group or the survival group according to prognosis. Blood flow of the brain was examined by TCD and analyzed for spectrum changes. The average blood flow velocity (Vm), pulse index (PI), and diastolic blood flow in reverse (RDF) were recorded and compared. RESULTS The data demonstrated that the average speed of bilateral middle cerebral artery blood flow in the brain death group was significantly reduced (Pbrain death group increased significantly. Moreover, RDF spectrum and nail-like sharp peak spectrum of the brain death group was higher than in the survival group. CONCLUSIONS Due to its simplicity, high repeatability, and specificity, TCD combined with other methods is highly valuable for diagnosis of brain death in patients with severe brain injury.

  14. Near-death-like experiences without life-threatening conditions or brain disorders: a hypothesis from a case report

    Directory of Open Access Journals (Sweden)

    Enrico eFacco

    2012-11-01

    Full Text Available Near-death experiences (NDEs are profound psychic experiences commonly occurring in life-threatening conditions. They include feeling a sense of peace, of seeing a bright light, encountering deceased relatives or religious figures, and of transcending space and time. To explain them, it has been suggested that they stem from brain disorders and/or psychological reactions to approaching death, a sort of wishful thinking in response to the perceived threat.This is a report on a case with most of the features typical of NDEs except that it occurred entirely without any life-threatening conditions. This evidence is theoretically incompatible with either of the above hypotheses, suggesting that a broader interpretation of the phenomenon is needed.

  15. Delayed cell death associated with mitotic catastrophe in γ-irradiated stem-like glioma cells

    Directory of Open Access Journals (Sweden)

    Esser Norbert

    2011-06-01

    Full Text Available Abstract Background and Purpose Stem-like tumor cells are regarded as highly resistant to ionizing radiation (IR. Previous studies have focused on apoptosis early after irradiation, and the apoptosis resistance observed has been attributed to reduced DNA damage or enhanced DNA repair compared to non-stem tumor cells. Here, early and late radioresponse of patient-derived stem-like glioma cells (SLGCs and differentiated cells directly derived from them were examined for cell death mode and the influence of stem cell-specific growth factors. Materials and methods Primary SLGCs were propagated in serum-free medium with the stem-cell mitogens epidermal growth factor (EGF and fibroblast growth factor-2 (FGF-2. Differentiation was induced by serum-containing medium without EGF and FGF. Radiation sensitivity was evaluated by assessing proliferation, clonogenic survival, apoptosis, and mitotic catastrophe. DNA damage-associated γH2AX as well as p53 and p21 expression were determined by Western blots. Results SLGCs failed to apoptose in the first 4 days after irradiation even at high single doses up to 10 Gy, but we observed substantial cell death later than 4 days postirradiation in 3 of 6 SLGC lines treated with 5 or 10 Gy. This delayed cell death was observed in 3 of the 4 SLGC lines with nonfunctional p53, was associated with mitotic catastrophe and occurred via apoptosis. The early apoptosis resistance of the SLGCs was associated with lower γH2AX compared to differentiated cells, but we found that the stem-cell culture cytokines EGF plus FGF-2 strongly reduce γH2AX levels. Nonetheless, in two p53-deficient SLGC lines examined γIR-induced apoptosis even correlated with EGF/FGF-induced proliferation and mitotic catastrophe. In a line containing CD133-positive and -negative stem-like cells, the CD133-positive cells proliferated faster and underwent more γIR-induced mitotic catastrophe. Conclusions Our results suggest the importance of delayed

  16. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

  17. One or two types of death? Attitudes of health professionals towards brain death and donation after circulatory death in three countries.

    Science.gov (United States)

    Rodríguez-Arias, D; Tortosa, J C; Burant, C J; Aubert, P; Aulisio, M P; Youngner, S J

    2013-08-01

    This study examined health professionals' (HPs) experience, beliefs and attitudes towards brain death (BD) and two types of donation after circulatory death (DCD)--controlled and uncontrolled DCD. Five hundred and eighty-seven HPs likely to be involved in the process of organ procurement were interviewed in 14 hospitals with transplant programs in France, Spain and the US. Three potential donation scenarios--BD, uncontrolled DCD and controlled DCD--were presented to study subjects during individual face-to-face interviews. Our study has two main findings: (1) In the context of organ procurement, HPs believe that BD is a more reliable standard for determining death than circulatory death, and (2) While the vast majority of HPs consider it morally acceptable to retrieve organs from brain-dead donors, retrieving organs from DCD patients is much more controversial. We offer the following possible explanations. DCD introduces new conditions that deviate from standard medical practice, allow procurement of organs when donors' loss of circulatory function could be reversed, and raises questions about "death" as a unified concept. Our results suggest that, for many HPs, these concerns seem related in part to the fact that a rigorous brain examination is neither clinically performed nor legally required in DCD. Their discomfort could also come from a belief that irreversible loss of circulatory function has not been adequately demonstrated. If DCD protocols are to achieve their full potential for increasing organ supply, the sources of HPs' discomfort must be further identified and addressed.

  18. IL-6 deficiency leads to reduced metallothionein-I+II expression and increased oxidative stress in the brain stem after 6-aminonicotinamide treatment

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2000-01-01

    We examined the effects of interleukin-6 (IL-6) deficiency on brain inflammation and the accompanying bone marrow (BM) leukopoiesis and spleen immune reaction after systemic administration of a niacin antagonist, 6-aminonicotinamide (6-AN), which causes both astroglial degeneration/cell death...... in brain stem gray matter areas and BM toxicity. In both normal and genetically IL-6-deficient mice (IL-6 knockout (IL-6KO) mice), the extent of astroglial degeneration/cell death in the brain stem was similar as determined from disappearance of GFAP immunoreactivity. In 6-AN-injected normal mice reactive...... astrocytosis encircled gray matter areas containing astroglial degeneration/cell death, which were infiltrated by several macrophages and some T-lymphocytes. Reactive astrocytes and a few macrophages increased significantly the antioxidants metallothionein-I+II (MT-I+II) and moderately the MT-III isoform. In 6...

  19. Single-photon emission computed tomography imaging for brain death donor counseling

    Directory of Open Access Journals (Sweden)

    Vijayanand Palaniswamy

    2016-01-01

    Full Text Available Organ donation awareness is very poor in India. We have a high demand for transplant organs with poor supply. Apnea test is the confirmatory test for brain death in our country. The Transplantation of Human Organs Act does not support any ancillary testing for the confirmation of brain death in our country. Radionuclide scan is used widely in western countries as a confirmatory test. We in our institution used this as a tool for family counseling with successful conversion rate.

  20. Transcranial Doppler ultransonography as a confirmative diagnostic test in brain death: a review

    OpenAIRE

    Ali Ünal; Babür Dora

    2012-01-01

    Before the invention of modern technologies death was defined as the cessation of cardiac and respiratoty functions. After the advances in mechanical ventilation and cardiopulmonary resucitation techniques the term “brain death” has been used instead and with the worldwide increase in cadaveric organ transplantation this term has increasingly gained importance. Brain death is a state which is diagnosed by neurological examination in patients who fulfill some specific criteria. In patients who...

  1. Apnea testing during brain death assessment: a review of clinical practice and published literature.

    Science.gov (United States)

    Scott, J Brady; Gentile, Michael A; Bennett, Stacey N; Couture, MaryAnn; MacIntyre, Neil R

    2013-03-01

    The diagnosis of brain death is a complex process. Strong knowledge of neurophysiology and an understanding of brain death etiology must be used to confidently determine brain death. The key findings in brain death are unresponsiveness, and absence of brainstem reflexes in the setting of a devastating neurological injury. These findings are coupled with a series of confirmatory tests, and the diagnosis of brain death is established based on consensus recommendations. The drive to breathe in the setting of an intense ventilatory stimulus (ie, respiratory acidosis) is a critical marker of brainstem function. As a consequence, apnea testing is an important component of brain death assessment. This procedure requires close monitoring of a patient as all ventilator support is temporarily removed and Paco2 levels are allowed to rise. A "positive" test is defined by a total absence of respiratory efforts under these conditions. While apnea testing is not new, it still lacks consensus standardization regarding the actual procedure, monitored parameters, and evidence-based safety measures that may be used to prevent complications. The purpose of this report is to provide an overview of apnea testing and discuss issues related to the administration and safety of the procedure.

  2. Brainstem death: A comprehensive review in Indian perspective.

    Science.gov (United States)

    Dhanwate, Anant Dattatray

    2014-09-01

    With the advent of cardiopulmonary resuscitation techniques, the cardiopulmonary definition of death lost its significance in favor of brain death. Brain death is a permanent cessation of all functions of the brain in which though individual organs may function but lack of integrating function of the brain, lack of respiratory drive, consciousness, and cognition confirms to the definition that death is an irreversible cessation of functioning of the organism as a whole. In spite of medical and legal acceptance globally, the concept of brain death and brain-stem death is still unclear to many. Brain death is not promptly declared due to lack of awareness and doubts about the legal procedure of certification. Many brain dead patients are kept on life supporting systems needlessly. In this comprehensive review, an attempt has been made to highlight the history and concept of brain death and brain-stem death; the anatomical and physiological basis of brain-stem death, and criteria to diagnose brain-stem death in India.

  3. Brainstem death: A comprehensive review in Indian perspective

    Directory of Open Access Journals (Sweden)

    Anant Dattatray Dhanwate

    2014-01-01

    Full Text Available With the advent of cardiopulmonary resuscitation techniques, the cardiopulmonary definition of death lost its significance in favor of brain death. Brain death is a permanent cessation of all functions of the brain in which though individual organs may function but lack of integrating function of the brain, lack of respiratory drive, consciousness, and cognition confirms to the definition that death is an irreversible cessation of functioning of the organism as a whole. In spite of medical and legal acceptance globally, the concept of brain death and brain-stem death is still unclear to many. Brain death is not promptly declared due to lack of awareness and doubts about the legal procedure of certification. Many brain dead patients are kept on life supporting systems needlessly. In this comprehensive review, an attempt has been made to highlight the history and concept of brain death and brain-stem death; the anatomical and physiological basis of brain-stem death, and criteria to diagnose brain-stem death in India.

  4. Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study

    Directory of Open Access Journals (Sweden)

    Rafael Simas

    2012-01-01

    Full Text Available OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of Pselectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30%, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70% reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals. CONCLUSION: The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage

  5. Brain death induces the alteration of liver protein expression profiles in rabbits.

    Science.gov (United States)

    Du, Bing; Li, Ling; Zhong, Zhibiao; Fan, Xiaoli; Qiao, Bingbing; He, Chongxiang; Fu, Zhen; Wang, Yanfeng; Ye, Qifa

    2014-08-01

    At present, there is no accurate method for evaluating the quality of liver transplant from a brain-dead donor. Proteomics are used to investigate the mechanisms involved in brain death‑induced liver injury and to identify sensitive biomarkers. In the present study, age‑ and gender‑matched rabbits were randomly divided into the brain death and sham groups. The sham served as the control. A brain‑death model was established using an intracranial progressive pressurized method. The differentially expressed proteins extracted from the liver tissues of rabbits that were brain‑dead for 6 h in the two groups were determined by two‑dimensional gel electrophoresis and matrix‑assisted laser desorption ionization time of flight mass spectrometry. Although there was no obvious functional and morphological difference in 2, 4 and 6 h after brain death, results of the proteomics analysis revealed 973±34 and 987±38 protein spots in the control and brain death groups, respectively. Ten proteins exhibited a ≥2‑fold alteration. The downregulated proteins were: aldehyde dehydrogenase, runt‑related transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate‑cysteine ligase regulatory subunit and microsomal cytochrome B5. By contrast, the expression of dihydropyrimidinase-related protein 4, peroxiredoxin‑6, 3‑phosphoinositide‑dependent protein kinase‑1, 3-mercaptopyruvate and alcohol dehydrogenase were clearly upregulated. Immunohistochemistry and western blot analysis results revealed that the expression of RUNX1 was gradually increased in a time‑dependent manner in 2, 4, and 6 h after brain death. In conclusion, alteration of the liver protein expression profile induced by brain death indicated the occurrence of complex pathological changes even if no functional or morphological difference was identified. Thus, RUNX1 may be a sensitive predict factor for evaluating the quality of brain death donated liver.

  6. Stem cells decreased neuronal cell death after hypoxic stress in primary fetal rat neurons in vitro.

    Science.gov (United States)

    Sakai, Tetsuro; Xu, Yan

    2012-01-01

    To explore stem cell-mediated neuronal protection through extracellular signaling pathways by transplanted stem cells, we sought to identify potential candidate molecules responsible for neuronal protection using an in vitro coculture system. Primary fetal rat hippocampal neurons underwent hypoxia (≤1% oxygen) for 96 h nad then were returned to a normoxic condition. The study group then received rat umbilical cord matrix-derived stem cells, while the control group received fresh media only. The experimental group showed decreased neuronal apoptosis compared to the control group [44.5 ± 1.6% vs. 71.0 ± 4.2% (mean ± SD, p = 0.0005) on day 5] and higher neuronal survival (4.9 ± 1.2 cells/100× field vs. 2.2 ± 0.3, p = 0.02 on day 5). Among 90 proteins evaluated using a protein array, stem cell coculture media showed increased protein secretion of TIMP-1 (5.61-fold), TIMP-2 (4.88), CNTF-Rα (3.42), activin A (2.20), fractalkine (2.04), CCR4 (2.02), and decreased secretion in MIP-2 (0.30-fold), AMPK α1 (0.43), TROY (0.48), and TIMP-3 (0.50). This study demonstrated that coculturing stem cells with primary neurons in vitro decreased neuronal cell death after hypoxia with significantly altered protein secretion. The results suggest that stem cells may offer neuronal protection through extracellular signaling.

  7. Brain and aviation: on the 80th anniversary of Constantin von Economo's (1876-1931) death.

    Science.gov (United States)

    Sak, Jarosław; Grzybowski, Andrzej

    2013-03-01

    2011 marks the 80th anniversary of the death of Constantin Alexander von Economo who conducted advanced research on the cytoarchitectonics of the brain. This Austrian neurologist and the pioneer of aviation described encephalitis lethargica, discovered the spindle neurons, and postulated the existence of the sleep and wakefulness centre in the brain. What is more he realized two of the biggest dreams of humankind: conquering space and getting to know the secrets of the human brain.

  8. Ethical controversies at end of life after traumatic brain injury: defining death and organ donation.

    Science.gov (United States)

    Souter, Michael; Van Norman, Gail

    2010-09-01

    Death is more than a mere biological occurrence. It has important legal, medical, and social ramifications that make it imperative that those who are responsible for determination of death be accurate and above suspicion. The medical and legal definitions of death have evolved to include consideration of such concepts as loss of integration of the whole organism, loss of autonomy, and loss of personhood. Development of the concept of brain death coincided with advances in medical technology that facilitated artificial ventilation and organ transplantation. More recently, the process of "timed" death with subsequent organ donation (controlled donation after cardiac death transplantation) has raised controversial questions having to do with the limits of treatments that facilitate organ transplant but might hasten death, and the duration of cardiac arrest necessary for declaration of death and the commencement of organ procurement. In this review, we discuss the background and ethical ramifications of the concepts of brain death, and of controversies involved in controlled donation after cardiac death organ transplantation.

  9. A Comparison of Brain Death Criteria between China and the United States

    Directory of Open Access Journals (Sweden)

    Ze-Yu Ding

    2015-01-01

    Full Text Available Background: Criteria for determining brain death (BD vary between China and the United States. We reported the results of an investigation designed to compare procedures to determine BD in two countries. Methods: The latest criteria in the United states were published in 2010. The latest criteria in China were published in 2009. We used these two types of BD criteria to evaluate patients who were considered to be BD. The time, cost, and accuracy of the diagnosis were compared. Results: From January 1, 2012 to October 8, 2013, there were 37 patients which were applied for BD evaluation in the Neurological Intensive Care Unit of Beijing Tiantan Hospital. The cause of coma were known as subarachnoid hemorrhage (18 patients, 48.6%, intracerebral hemorrhage (8 patients, 21.6%, cerebral ischemia (9 patients, 24.3%, brain stem tumor (1 patient, 2.7%, and intracranial infection (1 patient, 2.7%. The clinical examinations were done for all of the patients except 1 patient who had low blood pressure. Three patients had brainstem reflexes that were excluded from BD. Twenty-five patients had apnea tests, and 20 tests were completed that were all positive. Confirmatory tests were completed differently: Transcranial Doppler (30 patients, positive rate 86.7%, electroencephalogram (25 patients, positive rate 100%, and somatosensory evoked potential (16 patients, positive rate 100%. Thirty-three patients were diagnosed BD by criteria of the United States. Only 9 patients were diagnosed BD by Chinese criteria. The use of time and money in the USA criteria was obviously fewer than those in Chinese criteria (P = 0.000. Conclusion: Compared with BD criteria of the United States, Chinese criteria were stricter, lower positive rate, more cost in money and time, and more reliable by families and doctors.

  10. Controversies of diffusion weighted imaging in the diagnosis of brain death.

    Science.gov (United States)

    Luchtmann, Michael; Bernarding, Johannes; Beuing, Oliver; Kohl, Jana; Bondar, Imre; Skalej, Martin; Firsching, Raimund

    2013-10-01

    Imaging techniques as confirmatory tests may add safety to the diagnosis of brain death, but are partly not accepted either because they are too invasive, such as conventional arterial angiography, or because there is still lack of evidence of its reliability, such as magnetic resonance angiography. In this study the reliability of diffusion weighted imaging for the diagnosis of brain death was evaluated according in terms of its sensitivity and specificity. The apparent diffusion coefficients (ADC) of 18 brain dead patients were registered from 14 distinct brain areas. The mean ADC values of the brain dead patients were compared with normal controls of physiological ADC values of unaffected brain tissue. Despite a highly significant decrease of the mean ADC value in 16 patients, two patients showed mean ADC values that were within normal physiological range. An explanation may be the pseudonormalization of ADC values seen in stroke patients that depends on the time of the onset of the brain damage. We conclude, diffusion-weighted imaging may provide additional information on damage of the brain tissue but is not a practicable confirmatory test for the reliable diagnosis of brain death.

  11. Brain death and Islam: the interface of religion, culture, history, law, and modern medicine.

    Science.gov (United States)

    Miller, Andrew C; Ziad-Miller, Amna; Elamin, Elamin M

    2014-10-01

    How one defines death may vary. It is important for clinicians to recognize those aspects of a patient's religious beliefs that may directly influence medical care and how such practices may interface with local laws governing the determination of death. Debate continues about the validity and certainty of brain death criteria within Islamic traditions. A search of PubMed, Scopus, EMBASE, Web of Science, PsycNet, Sociological Abstracts, DIALOGUE ProQuest, Lexus Nexus, Google, and applicable religious texts was conducted to address the question of whether brain death is accepted as true death among Islamic scholars and clinicians and to discuss how divergent opinions may affect clinical care. The results of the literature review inform this discussion. Brain death has been acknowledged as representing true death by many Muslim scholars and medical organizations, including the Islamic Fiqh Academies of the Organization of the Islamic Conference and the Muslim World League, the Islamic Medical Association of North America, and other faith-based medical organizations as well as legal rulings by multiple Islamic nations. However, consensus in the Muslim world is not unanimous, and a sizable minority accepts death by cardiopulmonary criteria only.

  12. The degree of certainty in brain death: probability in clinical and Islamic legal discourse.

    Science.gov (United States)

    Qazi, Faisal; Ewell, Joshua C; Munawar, Ayla; Asrar, Usman; Khan, Nadir

    2013-04-01

    The University of Michigan conference "Where Religion, Policy, and Bioethics Meet: An Interdisciplinary Conference on Islamic Bioethics and End-of-Life Care" in April 2011 addressed the issue of brain death as the prototype for a discourse that would reflect the emergence of Islamic bioethics as a formal field of study. In considering the issue of brain death, various Muslim legal experts have raised concerns over the lack of certainty in the scientific criteria as applied to the definition and diagnosis of brain death by the medical community. In contrast, the medical community at large has not required absolute certainty in its process, but has sought to eliminate doubt through cumulative diagnostic modalities and supportive scientific evidence. This has recently become a principal model, with increased interest in data analysis and evidence-based medicine with the intent to analyze and ultimately improve outcomes. Islamic law has also long employed a systematic methodology with the goal of eliminating doubt from rulings regarding the question of certainty. While ample criticism of the scientific criteria of brain death (Harvard criteria) by traditional legal sources now exists, an analysis of the legal process in assessing brain death, geared toward informing the clinician's perspective on the issue, is lacking. In this article, we explore the role of certainty in the diagnostic modalities used to establish diagnoses of brain death in current medical practice. We further examine the Islamic jurisprudential approach vis-à-vis the concept of certainty (yaqīn). Finally, we contrast the two at times divergent philosophies and consider what each perspective may contribute to the global discourse on brain death, understanding that the interdependence that exists between the theological, juridical, ethical, and medical/scientific fields necessitates an open discussion and active collaboration between all parties. We hope that this article serves to continue the

  13. Utilizing pharmacotherapy and mesenchymal stem cell therapy to reduce inlfammation following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Sherwin Mashkouri; Marci G. Crowley; Michael G. Liska; Sydney Corey; Cesar V. Borlongan

    2016-01-01

    The pathologic process of chronic phase traumatic brain injury is associated with spreading inlfamma-tion, cell death, and neural dysfunction. It is thought that sequestration of inlfammatory mediators can facilitate recovery and promote an environment that fosters cellular regeneration. Studies have targeted post-traumatic brain injury inlfammation with the use of pharmacotherapy and cell therapy. These thera-peutic options are aimed at reducing the edematous and neurodegenerative inlfammation that have been associated with compromising the integrity of the blood-brain barrier. Although studies have yielded posi-tive results from anti-inlfammatory pharmacotherapy and cell therapy individually, emerging research has begun to target inlfammation using combination therapy. The joint use of anti-inlfammatory drugs along-side stem cell transplantation may provide better clinical outcomes for traumatic brain injury patients. Despite the promising results in this ifeld of research, it is important to note that most of the studies men-tioned in this review have completed their studies using animal models. Translation of this research into a clinical setting will require additional laboratory experiments and larger preclinical trials.

  14. Experimental study on the establishment and maintenance of brain death model with pigs

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shuijun; SHI Jihua; ZHAI Wenlong; SONG Yan; CHEN Shi

    2007-01-01

    It remains controversial that after the transplantation of using grafts from brain-dead donors,organs injury and rejection can influence the effects of transplantation.This study sought to explore methods of establishing a stable brain death(BD)model using Bama mini pigs and to maintain the brain-dead state for a comparatively long period to provide a model for investigating changes in brain death.Sixteen anesthetized Bama mini pigs were randomized into a control group(n=5)and a BD group(n=11).Intracranial pressure (ICP)was increased in a modified,slow,and intermittent way to establish BD.Respiration and circulation were sustained during the brain-dead state.Hemodynamic changes were monitored during the experiment.In the BD group,10 pigs met the requirements for brain death and 1 died of cardiopulmonary complications following an increase in ICP.Brain death was maintained for more than 48 hours with artificial life support.During the experiment,the heart rate and blood pressure showed characteristic changes due to increased ICP.Prior to BD being established,a"tic reaction"inevitably occurred.We used an improved method of increasing ICP to establish a stable BD model.The BD state could be maintained for more than 48 hours with effective respiratory and circulatory support.Disappearance of the tic reaction was considered to be one of the verified indexes for BD via encephalic pressure increase.

  15. [Determination of irreversibility of clinical brain death. Electroencephalography and evoked potentials].

    Science.gov (United States)

    Buchner, H; Ferbert, A

    2016-02-01

    Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

  16. Mesenteric hypoperfusion and inflammation induced by brain death are not affected by inhibition of the autonomic storm in rats

    Directory of Open Access Journals (Sweden)

    Rafael Simas

    2015-06-01

    Full Text Available OBJECTIVES: Brain death is typically followed by autonomic changes that lead to hemodynamic instability, which is likely associated with microcirculatory dysfunction and inflammation. We evaluated the role of the microcirculation in the hemodynamic and inflammatory events that occur after brain death and the effects of autonomic storm inhibition via thoracic epidural blockade on mesenteric microcirculatory changes and inflammatory responses. METHODS: Male Wistar rats were anesthetized and mechanically ventilated. Brain death was induced via intracranial balloon inflation. Bupivacaine (brain death-thoracic epidural blockade group or saline (brain death group infusion via an epidural catheter was initiated immediately before brain death induction. Sham-operated animals were used as controls (SH group. The mesenteric microcirculation was analyzed via intravital microscopy, and the expression of adhesion molecules was evaluated via immunohistochemistry 180 min after brain death induction. RESULTS: A significant difference in mean arterial pressure behavior was observed between the brain death-thoracic epidural blockade group and the other groups, indicating that the former group experienced autonomic storm inhibition. However, the proportion of perfused small vessels in the brain death-thoracic epidural blockade group was similar to or lower than that in the brain death and SH groups, respectively. The expression of intercellular adhesion molecule 1 was similar between the brain death-thoracic epidural blockade and brain death groups but was significantly lower in the SH group than in the other two groups. The number of migrating leukocytes in the perivascular tissue followed the same trend for all groups. CONCLUSIONS: Although thoracic epidural blockade effectively inhibited the autonomic storm, it did not affect mesenteric hypoperfusion or inflammation induced by brain death.

  17. Donor pretreatment with carbamylated erythropoietin in a brain death model reduces inflammation more effectively than erythropoietin while preserving renal function

    NARCIS (Netherlands)

    Nijboer, Willemijn N.; Ottens, Petra J.; van Dijk, Antony; van Goor, Harry; Ploeg, Rutger J.; Leuvenink, Henri G. D.

    2010-01-01

    Objective: We hypothesized that donor treatment of deceased brain dead donors would lead to a decrease in inflammatory responses seen in brain death and lead to a restoration of kidney function. Design: A standardized slow-induction rat brain death model followed by evaluation of kidney function in

  18. Donor pretreatment with carbamylated erythropoietin in a brain death model reduces inflammation more effectively than erythropoietin while preserving renal function.

    NARCIS (Netherlands)

    Nijboer, W.N.; Ottens, P.J.; Dijk, A.P.J. van; Goor, H. van; Ploeg, R.J.; Leuvenink, H.G.

    2010-01-01

    OBJECTIVE: We hypothesized that donor treatment of deceased brain dead donors would lead to a decrease in inflammatory responses seen in brain death and lead to a restoration of kidney function. DESIGN: A standardized slow-induction rat brain death model followed by evaluation of kidney function in

  19. Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Raul Chavez-Valdez

    2012-01-01

    Full Text Available Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis “continuum” in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3 leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI.

  20. East-West differences in perception of brain death. Review of history, current understandings, and directions for future research.

    Science.gov (United States)

    Yang, Qing; Miller, Geoffrey

    2015-06-01

    The concept of brain death as equivalent to cardiopulmonary death was initially conceived following developments in neuroscience, critical care, and transplant technology. It is now a routine part of medicine in Western countries, including the United States. In contrast, Eastern countries have been reluctant to incorporate brain death into legislation and medical practice. Several countries, most notably China, still lack laws recognizing brain death and national medical standards for making the diagnosis. The perception is that Asians are less likely to approve of brain death or organ transplant from brain dead donors. Cultural and religious traditions have been referenced to explain this apparent difference. In the West, the status of the brain as home to the soul in Enlightenment philosophy, combined with pragmatism and utilitarianism, supports the concept of brain death. In the East, the integration of body with spirit and nature in Buddhist and folk beliefs, along with the Confucian social structure that builds upon interpersonal relationships, argues against brain death. However, it is unclear whether these reasoning strategies are explicitly used when families and medical providers are faced with acknowledging brain death. Their decisions are more likely to involve a prioritization of values and a rationalization of intuitive responses. Why and whether there might be differences between East and West in the acceptance of the brain death concept requires further empirical testing, which would help inform policy-making and facilitate communication between providers and patients from different cultural and ethnic backgrounds.

  1. Apnea testing, a simple prognostic test for diagnosis of brain death

    Directory of Open Access Journals (Sweden)

    Nemat Bilan

    2014-05-01

    Full Text Available Introduction: Brain-death is the end stage of most illnesses that cause brain injury and decrease oxygenation and circulation of brain tissues. Early determination of brain-death isessential to the prevention of expensive modeling in the pediatric intensive care unit (PICUand reserving facilities for patients with good prognosis. Apnea test is one of the importantbrain-death determining methods in clinical evaluation that can be performed easier and fasterthan other methods. Methods: In a cross-sectional study, 75 patients with brain-death criteria were evaluated from2003-2011. Apnea testing was fulfilled through standard methods. Patients who did not develop spontaneous respiration at PaCo level of 60 mmHg or more were confirmed as brain-dead. Results: Mean age of patients was 40 months. All patients were comatose, without brainstemreflexes. Cause of coma was status epilepticus in most patients. All patients that had a positive apnea test died after a mean duration of 8 days.Conclusion: All other confirmative methods, irrespective of their accuracy, need complexinstruments and experienced manpower, and are expensive which makes their preparation impossible in most ICU centers. However, apnea test is a simple prognostic method in braindeathconfirmationwith100%accuracy.​

  2. A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sandhya eRavikumar

    2016-04-01

    Full Text Available We describe a case report of fulminant Guillain-Barré syndrome mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy (AMAN, a subtype of Guillain-Barré syndrome, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler ultrasound showed appropriate blood flow to the brain. Guillain-Barré syndrome rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and transcranial dopplers when uncertainty exists about the reliability of the clinical exam.

  3. A case of a brain stem abscess with a favorable outcome

    NARCIS (Netherlands)

    Bulthuis, Vincent J; Gubler, Felix S; Teernstra, Onno P M; Temel, Yasin

    2015-01-01

    BACKGROUND: A brain stem abscess is a rare and severe medical condition. Here, we present a rare case of a brain stem abscess in a young pregnant woman, requiring acute stereotactic intervention. CASE DESCRIPTION: A 36-year-old woman presented with a headache, nausea, and vomiting, and computed tomo

  4. IS BRAIN DEATH REVERSAL POSSIBLE IN NEAR FUTURE: INTRATHECAL SODIUM NITROPRUSSIDE (SNP SUPERFUSION IN BRAIN DEATH PATIENTS = THE 10,000 FOLD EFFECT

    Directory of Open Access Journals (Sweden)

    Vinod

    2014-05-01

    Full Text Available BACKGROUND: Primary or secondary brain death is accompanied with vasospasm of the perforators & further exaggerating the anoxic damage, in the form of neuropraxia. In normal conditions the excitatory impulse propagates as anterograde neurotransmission (ANT and at the level of synapse, glutamate activates NMDA receptors on postsynaptic membrane. Nitric oxide (NO is produced by Nitric oxide Synthetase (NOS in postsynaptic dendride or cell body and travels backwards across a chemical synapse to bind to the axon terminal of a presynaptic neuron for regulation of ANT this process is called as the retrograde neurotransmission (RNT. Thus the primary function of NO is RNT and the purpose of RNT is regulation of chemical neurotransmission at synapse. For this reason, RNT allows neural circuits to create feedback loops. The haem is the ligand binding site of NO receptor (sGC at presynaptic membrane. The affinity of haem exhibits >10, 000- fold excess for NO than Oxygen (THE 10, 000 FOLD EFFECT. In pathological conditions ANT, normal synaptic activity including RNT is absent. NO donors like sodium nitroprusside (SNP releases NO by activating NOS at the level of postsynaptic area. NO now travels backwards across a chemical synapse to bind to the haem of NO receptor at axon terminal of a presynaptic neuron as in normal condition. NO now acts as impulse generator (at presynaptic membrane thus bypasses the normal ANT. Also the arteriolar perforators are having Nitric Oxide Synthetase (NOS at the adventitial side (outer border on which sodium nitroprusside (SNP acts; causing release of Nitric Oxide (NO which vasodilates the perforators causing gush of blood in brain’s tissue and reversal of brain death. OBJECTIVE: In brain death cases we only think for various transplantations but this study being a pilot study reverses some criteria of brain death by vasodilating the arteriolar perforators. To study the effect of intrathecal sodium nitroprusside (IT SNP in

  5. Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Jindou Jiang; Xingyao Bu; Meng Liu; Peixun Cheng

    2012-01-01

    Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury.

  6. IL-13Ra2- and glioma stem cell-pulsed dendritic cells induce glioma cell death in vitro

    Institute of Scientific and Technical Information of China (English)

    Ying Wang; Ruifan Xie; Hongquan Niu; Ting Lei

    2016-01-01

    Objective Gliomas are the most common malignant tumors in the central nervous system. Despite mul-tiple therapies including surgery, chemotherapy, and radiotherapy, the prognosis of patients remains poor. Immunotherapy is an alternative method of treating glioma, and the use of dendritic cel vaccines is one of the promising treatment options. However, there is no specific tumor cel antigen that can trigger dendritic cel s (DCs). IL-13Ra2 is a specific antigen expressed in glioma cel s; in the current study, we have at-tempted to explore whether IL-13Ra2 could be the antigen that triggers DCs and to envisage its application as potential therapy for glioma. Methods The expression of IL-13Ra2 was detected in U251 glioma cel lines and primary glioma tissues using dif erent methods. DCs from human blood were isolated and pulsed with recombinant IL-13Ra2, fol-lowing which the cytotoxicity of these DCs on glioma cel s was detected and analyzed. Results About 55.9% human glioma tissue cel s expressed IL-13Ra2, while normal brain tissue cel s did not show any expression. DC vaccines loaded with IL-13Ra2, glioma cel antigen, and brain tumor stem cel (BTSC) antigen could significantly stimulate the proliferation of T lymphocytes and induce cel death in the glioma tissue. Compared to other groups, DC vaccines loaded with BTSC antigen showed the strongest ability to activate cytotoxic T lymphocytes (CTLs), while the glioma cel antigen group showed no significant dif erence. Conclusion IL-13Ra2, which is expressed in gliomas and by glioma stem cel s, as wel as IL-13Ra2 could prove to be potential antigens for DC vaccine-based immunotherapy.

  7. Cell death in the injured brain: roles of metallothioneins

    DEFF Research Database (Denmark)

    Pedersen, Mie Ø; Larsen, Agnete; Stoltenberg, Meredin;

    2009-01-01

    oxygen species (ROS). ROS promote oxidative stress, which leads to neurodegeneration and ultimately results in programmed cell death (secondary injury). Since this delayed, secondary tissue loss occurs days to months following the primary injury it provides a therapeutic window where potential......, and caspase inhibitors. However, most of the scientific efforts have failed in translating the experimental results into clinical trials. Despite intensive research, effective neuroprotective therapies are lacking in the clinic, and TBI continues to be a major cause of morbidity and mortality. This paper...

  8. The "hot nose" sign on brain death nuclear scintigraphy: where does the flow really go?

    Science.gov (United States)

    Appelt, Eric A; Song, Won S; Phillips, William T; Metter, Darlene F; Salman, Umber A; Blumhardt, Ralph

    2008-01-01

    Nuclear scintigraphy has been used in patients with brain death since the 1970s. Many studies report a "hot nose" sign as predictive of brain death and lack of cerebral flow. Current nuclear medicine textbooks state that increased flow to the nose occurs secondary to occlusion of the internal carotid artery with flow rerouted to the nose via the external carotid artery. This explanation has been provided for decades assuming that the blood flow is actually increased to the nose. We performed a study to determine whether flow is really seen in the nose when a hot nose sign is present.

  9. [About the introduction the criteria of brain death in Poland in 1984].

    Science.gov (United States)

    Paprocka-Lipińska, Anna

    2016-09-29

    Significant recovery of discussion about the need for the formulation of criteria of death was provoked due to the progress of medicine. Development of anaesthesiology and intensive therapy, introduction of new resuscitation techniques and devices, which are increasingly better able to maintain and sometimes even replace functions of the respiratory or cardiovascular system, which are essential for the survival meant that existing for centuries, socially accepted classical criteria of death, based on cessation of breath and circulation, are no longer sufficient. The criteria of brain death developed by the Ad Hoc Committee - 12-experts commission at Harvard University, published in Journal of American Medical Association in August 1968 and were the breaking point. The concept has been adopted and accepted by society in many countries soon, while in Poland the process of formulating and introduction of criteria for brain death took much more time. Based on the available literature and preserved archival materials, this article describing the process of development of new death criteria, acceptance by the National Team of Specialists and publication in 1984 the announcement by the Minister of Health and Social Welfare about the criteria of brain death.

  10. The profile of head injuries and traumatic brain injury deaths in Kashmir

    Directory of Open Access Journals (Sweden)

    Tabish Amin

    2008-06-01

    Full Text Available Abstract This study was conducted on patients of head injury admitted through Accident & Emergency Department of Sher-i-Kashmir Institute of Medical Sciences during the year 2004 to determine the number of head injury patients, nature of head injuries, condition at presentation, treatment given in hospital and the outcome of intervention. Traumatic brain injury (TBI deaths were also studied retrospectively for a period of eight years (1996 to 2003. The traumatic brain injury deaths showed a steady increase in number from year 1996 to 2003 except for 1999 that showed decline in TBI deaths. TBI deaths were highest in age group of 21–30 years (18.8%, followed by 11–20 years age group (17.8% and 31–40 years (14.3%. The TBI death was more common in males. Maximum number of traumatic brain injury deaths was from rural areas as compared to urban areas. To minimize the morbidity and mortality resulting from head injury there is a need for better maintenance of roads, improvement of road visibility and lighting, proper mechanical maintenance of automobile and other vehicles, rigid enforcement of traffic rules, compulsory wearing of crash helmets by motor cyclist and scooterists and shoulder belt in cars and imparting compulsory road safety education to school children from primary education level. Moreover, appropriate medical care facilities (including trauma centres need to be established at district level, sub-divisional and block levels to provide prompt and quality care to head injury patients

  11. The profile of head injuries and traumatic brain injury deaths in Kashmir.

    Science.gov (United States)

    Yattoo, Gh; Tabish, Amin

    2008-01-01

    This study was conducted on patients of head injury admitted through Accident & Emergency Department of Sher-i-Kashmir Institute of Medical Sciences during the year 2004 to determine the number of head injury patients, nature of head injuries, condition at presentation, treatment given in hospital and the outcome of intervention. Traumatic brain injury (TBI) deaths were also studied retrospectively for a period of eight years (1996 to 2003).The traumatic brain injury deaths showed a steady increase in number from year 1996 to 2003 except for 1999 that showed decline in TBI deaths. TBI deaths were highest in age group of 21-30 years (18.8%), followed by 11-20 years age group (17.8%) and 31-40 years (14.3%). The TBI death was more common in males. Maximum number of traumatic brain injury deaths was from rural areas as compared to urban areas.To minimize the morbidity and mortality resulting from head injury there is a need for better maintenance of roads, improvement of road visibility and lighting, proper mechanical maintenance of automobile and other vehicles, rigid enforcement of traffic rules, compulsory wearing of crash helmets by motor cyclist and scooterists and shoulder belt in cars and imparting compulsory road safety education to school children from primary education level. Moreover, appropriate medical care facilities (including trauma centres) need to be established at district level, sub-divisional and block levels to provide prompt and quality care to head injury patients.

  12. Neural activity control of neural stem cells and SVZ niche response to brain injury

    OpenAIRE

    Páez González, Patricia

    2014-01-01

    Patricia Paez-Gonzalez Kuo Lab, Dept. of Cell Biology, Duke University Medical Center, NC,USA. Date: 11/16/2014 Utilizing stem cells in the adult brain hold great promise for regenerative medicine. Harnessing ability of adult neural stem cells (NSCs) to generate new neurons or other types of brain cells may provide much needed therapies for patients suffering from brain injuries or neuro-degenerative diseases such as Parkinson’s, Scizophrenia, or Alzheimer’s disease. However...

  13. Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure.

    Science.gov (United States)

    Legrand, M; Elie, C; Stefani, J; N Florès; Culeux, C; Delissen, O; Ibanez, C; Lestaevel, P; Eriksson, P; Dinocourt, C

    2016-01-01

    The developing brain is more susceptible to neurotoxic compounds than adult brain. It is also well known that disturbances during brain development cause neurological disorders in adulthood. The brain is known to be a target organ of uranium (U) exposure and previous studies have noted that internal U contamination of adult rats induces behavioral disorders as well as affects neurochemistry and neurophysiological properties. In this study, we investigated whether depleted uranium (DU) exposure affects neurogenesis during prenatal and postnatal brain development. We examined the structural morphology of the brain, cell death and finally cell proliferation in animals exposed to DU during gestation and lactation compared to control animals. Our results showed that DU decreases cell death in the cortical neuroepithelium of gestational day (GD) 13 embryos exposed at 40mg/L and 120mg/L and of GD18 fetuses exposed at 120mg/L without modification of the number of apoptotic cells. Cell proliferation analysis showed an increase of BrdU labeling in the dentate neuroepithelium of fetuses from GD18 at 120mg/L. Postnatally, cell death is increased in the dentate gyrus of postnatal day (PND) 0 and PND5 exposed pups at 120mg/L and is associated with an increase of apoptotic cell number only at PND5. Finally, a decrease in dividing cells is observed in the dentate gyrus of PND21 rats developmentally exposed to 120mg/L DU, but not at PND0 and PND5. These results show that DU exposure during brain development causes opposite effects on cell proliferation and cell death processes between prenatal and postnatal development mainly at the highest dose. Although these modifications do not have a major impact in brain morphology, they could affect the next steps of neurogenesis and thus might disrupt the fine organization of the neuronal network.

  14. Prospects and Limitations of Using Endogenous Neural Stem Cells for Brain Regeneration

    OpenAIRE

    Kazunobu Sawamoto; Eisuke Kako; Naoko Kaneko

    2011-01-01

    Neural stem cells (NSCs) are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunologica...

  15. Protein aggregation in association with delayed neuronal death in rat model of brain ischemia

    Institute of Scientific and Technical Information of China (English)

    Pengfei GE; Tianfei LUG; Shuanglin FU; Wenchen LI; Chonghao WANG; Chuibing ZHOU; Yinan LUO

    2008-01-01

    To investigate the relationship between protein aggregation and delayed neuronal death, we adopted rat models of 20 min ischemia. Brain ischemia was produced using the 2-vessel occlusion (2VO) model in rats Light microscopy, transmission electronic microscopy and Western blot analysis were performed for morphological analysis of neurons, and protein detection. The results showed delayed neuronal death took place at 72 h after ischemia-reperfusion, protein aggregates formed at 4 h after reperfusion and reached the peak at 24 h after reper-fusion, and Western blot analysis was consistent with transmission electronic microscopy. We conclude that protein aggregation is one of the important factors leading to delayed neuronal death.

  16. Objective evaluation of fourth ventricle displacement in brain CT findings. 4 cases of brain stem tumor

    Energy Technology Data Exchange (ETDEWEB)

    Okino, Fumiko; Eguchi, Tsuyako; Shinohara, Teruo; Hatano, Mitsunori (Yamaguchi Univ., Ube (Japan). School of Medicine)

    1983-11-01

    Distance between the ridge of the sella turcica and the anterior wall of the fourth ventricle (a) and the distance between the ridge of the sella and the posterior pole in the occipital region (b) were measured on the slice visualizing the fourth ventricle and sella. The location of the fourth ventricle was expressed by a/b, and its normal value was calculated for comparison with that in a patient group. The a/b values of the control group were in the range of 0.33 and 0.48 with a mean +- SD of 0.41+-0.3 and was not subject to the influences of age, sex distinction, cranial shape or slicing direction. The a/b values of the patient group were all abnormal (more than mean +- 2SD of the control group) on initial CT and showed an increase with progress of the disease activity. Measurement of the a/b on brain CT was thought to serve as a useful indicator for early detection and follow-up of the course of lesions occupying the brain stem (especially brain stem tumors).

  17. Furan fatty acids efficiently rescue brain cells from cell death induced by oxidative stress

    NARCIS (Netherlands)

    Teixeira, A.; Cox, R.C.; Egmond, M.R.

    2013-01-01

    Treatment of rat brain C6 astroglioma cells with furan fatty acid F6 prior to exposure to hydrogen peroxide shows a strong protective effect of F6 against cell death resulting from oxidative stress. This protective effect is obtained only for F6 administered as a free fatty acid and with an intact f

  18. Slow induction of brain death leads to decreased renal function and increased hepatic apoptosis in rats

    NARCIS (Netherlands)

    Rebolledo, Rolando A.; Hoeksma, Dane; Hottenrott, Christina M. V.; Bodar, Yves J. L.; Ottens, Petra J.; Wiersema-Buist, Janneka; Leuvenink, Henri G. D.

    2016-01-01

    Background: Donor brain death (BD) is an independent risk factor for graft survival in recipients. While in some patients BD results from a fast increase in intracranial pressure, usually associated with trauma, in others, intracranial pressure increases more slowly. The speed of intracranial pressu

  19. Beacon signal in transcranial color coded ultrasound: A sign for brain death

    Directory of Open Access Journals (Sweden)

    Mehmet Akif Topçuoğlu

    2014-04-01

    Full Text Available A widely under-recognized brain-death confirming transcranial ultrasonography pattern resembling the red-blue beacon signal was demonstrated. Familiarity to this distinct and characteristic ultrasonic pattern seems to be important in the perspective of point-of-care neurological ultrasound use and knobology.

  20. Donor treatment after pronouncement of brain death: a neglected intensive care problem.

    Science.gov (United States)

    Wijnen, R M; van der Linden, C J

    1991-09-01

    The need for cadaveric organs for transplantation is increasing. To decrease the shortage of organs, identification of potential donors and conditioning of these donors must improve. We present a review of relevant data on body and tissue alterations due to brain death and summarize the recent literature covering experimental and clinical studies on optimal donor management.

  1. A Comparison of Brain Death Criteria between China and the United States

    Institute of Scientific and Technical Information of China (English)

    Ze-Yu Ding; Qian Zhang; Jian-Wei Wu; Zhong-Hua Yang; Xing-Quan Zhao

    2015-01-01

    Background:Criteria for determining brain death (BD) vary between China and the United States.We reported the results of an investigation designed to compare procedures to determine BD in two countries.Methods:The latest criteria in the United states were published in 2010.The latest criteria in China were published in 2009.We used these two types of BD criteria to evaluate patients who were considered to be BD.The time,cost,and accuracy of the diagnosis were compared.Results:From January 1,2012 to October 8,2013,there were 37 patients which were applied for BD evaluation in the Neurological Intensive Care Unit of Beijing Tiantan Hospital.The cause of coma were known as subarachnoid hemorrhage (18 patients,48.6%),intracerebral hemorrhage (8 patients,21.6%),cerebral ischemia (9 patients,24.3%),brain stem tumor (1 patient,2.7%),and intracranial infection (1 patient,2.7%).The clinical examinations were done for all of the patients except 1 patient who had low blood pressure.Three patients had brainstem reflexes that were excluded from BD.Twenty-five patients had apnea tests,and 20 tests were completed that were all positive.Confirmatory tests were completed differently:Transcranial Doppler (30 patients,positive rate 86.7%),electroencephalogram (25 patients,positive rate 100%),and somatosensory evoked potential (16 patients,positive rate 100%).Thirty-three patients were diagnosed BD by criteria of the United States.Only 9 patients were diagnosed BD by Chinese criteria.The use of time and money in the USA criteria was obviously fewer than those in Chinese criteria (P =0.000).Conclusion:Compared with BD criteria of the United States,Chinese criteria were stricter,lower positive rate,more cost in money and time,and more reliable by families and doctors.

  2. Biological effect of velvet antler polypeptides on neural stem cells from embryonic rat brain

    Institute of Scientific and Technical Information of China (English)

    LU Lai-jin; CHEN Lei; MENG Xiao-ting; YANG Fan; ZHANG Zhi-xin; CHEN Dong

    2005-01-01

    Background Velvet antler polypeptides (VAPs), which are derived from the antler velvets, have been reported to maintain survival and promote growth and differentiation of neural cells and, especially the development of neural tissues. This study was designed to explore the influence of VAPs on neural stem cells in vitro derived from embryonic rat brain. Methods Neural stem cells derived from E12-14 rat brain were isolated, cultured, and expanded for 7 days until neural stem cell aggregations and neurospheres were generated. The neurospheres were cultured under the condition of different concentration of VAPs followed by immunocytochemistry to detect the differentiation of neural stem cells. Results VAPs could remarkablely promote differentiation of neural stem cells and most neural stem cells were induced to differentiate towards the direction of neurons under certain concentration of VAPs.Conclusion Neural stem cells can be successfully induced into neurons by VAPs in vitro, which could provide a basis for regeneration of the nervous system.

  3. Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain.

    Science.gov (United States)

    Barbosa, Joana S; Sanchez-Gonzalez, Rosario; Di Giaimo, Rossella; Baumgart, Emily Violette; Theis, Fabian J; Götz, Magdalena; Ninkovic, Jovica

    2015-05-15

    Adult neural stem cells are the source for restoring injured brain tissue. We used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. We observed an imbalance of direct conversion consuming the stem cells and asymmetric and symmetric self-renewing divisions, leading to depletion of stem cells over time. After brain injury, neuronal progenitors are recruited to the injury site. These progenitors are generated by symmetric divisions that deplete the pool of stem cells, a mode of neurogenesis absent in the intact telencephalon. Our analysis revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration.

  4. Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells.

    Science.gov (United States)

    Flygt, Johanna; Gumucio, Astrid; Ingelsson, Martin; Skoglund, Karin; Holm, Jonatan; Alafuzoff, Irina; Marklund, Niklas

    2016-06-01

    Oligodendrocyte (OL) death may contribute to white matter pathology, a common cause of network dysfunction and persistent cognitive problems in patients with traumatic brain injury (TBI). Oligodendrocyte progenitor cells (OPCs) persist throughout the adult CNS and may replace dead OLs. OL death and OPCs were analyzed by immunohistochemistry of human brain tissue samples, surgically removed due to life-threatening contusions and/or focal brain swelling at 60.6 ± 75 hours (range 4-192 hours) postinjury in 10 severe TBI patients (age 51.7 ± 18.5 years). Control brain tissue was obtained postmortem from 5 age-matched patients without CNS disorders. TUNEL and CC1 co-labeling was used to analyze apoptotic OLs, which were increased in injured brain tissue (p number of single-labeled Olig2, A2B5, NG2, and PDGFR-α-positive cells, numbers of Olig2 and A2B5 co-labeled cells were increased in TBI samples (p < 0.05); this was inversely correlated with time from injury to surgery (r = -0.8, p < 0.05). These results indicate that severe focal human TBI results in OL death and increases in OPCs postinjury, which may influence white matter function following TBI.

  5. Kidney Injury Molecule-1 is an Early Noninvasive Indicator for Donor Brain Death-Induced Injury Prior to Kidney Transplantation

    NARCIS (Netherlands)

    Nijboer, W. N.; Schuurs, T. A.; Damman, J.; van Goor, H.; Vaidya, V. S.; van der Heide, J. J. Homan; Leuvenink, H. G. D.; Bonventre, J. V.; Ploeg, R. J.

    2009-01-01

    In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In huma

  6. Factors associated with attitude and hypothetical behaviour regarding brain death and organ transplantation: comparison between medical and other university students.

    Science.gov (United States)

    Ohwaki, Kazuhiro; Yano, Eiji; Shirouzu, Makiko; Kobayashi, Aya; Nakagomi, Tadayoshi; Tamura, Akira

    2006-01-01

    The aim of this study was to investigate the factors, including knowledge, that determine an individual's attitudes and behaviours regarding brain death and organ transplantation using questionnaires among medical and other university students. A total of 522 students (388 medical and 134 other) answered a questionnaire. The survey included the individual's knowledge about brain death, attitudes towards brain death and organ transplantation, and hypothetical behaviours assuming their willingness to donate their own or their family's organs. Medical students were more likely to have knowledge about brain death and to accept brain death and organ transplantation compared with other students, while there was no difference in their willingness to donate their own or their family's organs. Logistic regression analysis was used to assess the effects of various factors on the attitudes and behaviours. In both medical and other students, confidence in brain-death diagnosis by doctors was independently associated with their willingness to donate their own organs after the adjustment for other factors, including knowledge (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.15 to 2.97 and OR, 4.97; 95% CI, 1.01 to 24.39, respectively). An increase in knowledge may cause positive attitudes towards brain death and organ transplant. Meanwhile, reducing uncertainty about the brain-death diagnostic process might have a beneficial effect on the willingness to donate organs.

  7. Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

    Science.gov (United States)

    Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

    2016-01-01

    Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

  8. Analyzing EEG of quasi-brain-death based on dynamic sample entropy measures.

    Science.gov (United States)

    Ni, Li; Cao, Jianting; Wang, Rubin

    2013-01-01

    To give a more definite criterion using electroencephalograph (EEG) approach on brain death determination is vital for both reducing the risks and preventing medical misdiagnosis. This paper presents several novel adaptive computable entropy methods based on approximate entropy (ApEn) and sample entropy (SampEn) to monitor the varying symptoms of patients and to determine the brain death. The proposed method is a dynamic extension of the standard ApEn and SampEn by introducing a shifted time window. The main advantages of the developed dynamic approximate entropy (DApEn) and dynamic sample entropy (DSampEn) are for real-time computation and practical use. Results from the analysis of 35 patients (63 recordings) show that the proposed methods can illustrate effectiveness and well performance in evaluating the brain consciousness states.

  9. Activation and modulation of cardiac poly-adenosine diphosphate ribose polymerase activity in a rat model of brain death.

    Science.gov (United States)

    Brain, John G; Rostron, Anthony J; Dark, John H; Kirby, John A

    2008-05-15

    DNA damage during transplantation can activate poly-adenosine diphosphate ribose polymerase (PARP) resulting in the generation of polymers of adenosine diphosphate-ribose (PAR). Excessive linkage of PAR to nuclear proteins can induce cell death, thereby limiting the function of transplanted organs. This study uses a rat model of brain death to determine the profile of PARP activation and whether mechanisms that lead to cell death can be ameliorated by appropriate donor resuscitation. The expression of PAR-linked nuclear proteins within cardiac myocytes was greatly increased after the induction of donor brain death. Importantly, infusion of noradrenaline or vasopressin to normalize the chronic hypotension produced by brain death reduced the expression of PAR to a level below baseline. These data suggest that chronic hypotension after donor brain death has the potential to limit cardiac function through the activation of PARP; however, this early cause of graft damage can be mitigated by appropriate donor resuscitation.

  10. Killing by organ procurement: brain-based death and legal fictions.

    Science.gov (United States)

    Veatch, Robert M

    2015-06-01

    The dead donor rule (DDR) governs procuring life-prolonging organs. They should be taken only from deceased donors. Miller and Truog have proposed abandoning the rule when patients have decided to forgo life-sustaining treatment and have consented to procurement. Organs could then be procured from living patients, thus killing them by organ procurement. This proposal warrants careful examination. They convincingly argue that current brain or circulatory death pronouncement misidentifies the biologically dead. After arguing convincingly that physicians already cause death by withdrawing treatment, they claim no bright-line differences preclude organ removal from the living. The argument fails for those who accept the double effect doctrine or other grounds for distinguishing forgoing life support from active, intentional killing. If the goal is determining irreversible loss of somatic function, they correctly label current death pronouncement a "legal fiction." Recognizing a second, public policy meaning of the term death provides grounds for maintaining the DDR without jeopardizing procurement.

  11. NFL-lipid nanocapsules for brain neural stem cell targeting in vitro and in vivo.

    Science.gov (United States)

    Carradori, Dario; Saulnier, Patrick; Préat, Véronique; des Rieux, Anne; Eyer, Joel

    2016-09-28

    The replacement of injured neurons by the selective stimulation of neural stem cells in situ represents a potential therapeutic strategy for the treatment of neurodegenerative diseases. The peptide NFL-TBS.40-63 showed specific interactions towards neural stem cells of the subventricular zone. The aim of our work was to produce a NFL-based drug delivery system able to target neural stem cells through the selective affinity between the peptide and these cells. NFL-TBS.40-63 (NFL) was adsorbed on lipid nanocapsules (LNC) whom targeting efficiency was evaluated on neural stem cells from the subventricular zone (brain) and from the central canal (spinal cord). NFL-LNC were incubated with primary neural stem cells in vitro or injected in vivo in adult rat brain (right lateral ventricle) or spinal cord (T10). NFL-LNC interactions with neural stem cells were different depending on the origin of the cells. NFL-LNC showed a preferential uptake by neural stem cells from the brain, while they did not interact with neural stem cells from the spinal cord. The results obtained in vivo correlate with the results observed in vitro, demonstrating that NFL-LNC represent a promising therapeutic strategy to selectively deliver bioactive molecules to brain neural stem cells.

  12. Phenethyl isothiocyanate upregulates death receptors 4 and 5 and inhibits proliferation in human cancer stem-like cells

    OpenAIRE

    Wang, Dan; Upadhyaya, Bijaya; Liu, Yi; Knudsen, David; Dey, Moul

    2014-01-01

    Background The cytokine TRAIL (tumor necrotic factor-related apoptosis-inducing ligand) selectively induces apoptosis in cancer cells, but cancer stem cells (CSCs) that contribute to cancer-recurrence are frequently TRAIL-resistant. Here we examined hitherto unknown effects of the dietary anti-carcinogenic compound phenethyl isothiocyanate (PEITC) on attenuation of proliferation and tumorigenicity and on up regulation of death receptors and apoptosis in human cervical CSC. Methods Cancer stem...

  13. Electro-Acupuncture for Treatment of Dysequillibrium Due to Cerebellum or Brain Stem Infarction

    Institute of Scientific and Technical Information of China (English)

    赵宏; 刘志顺; 刘效娟

    2003-01-01

    @@ The authors treated 26 cases of dysequillibrium due tocerebellum or brain stem infarction byelectro-acupuncture from Aug 2000 - April 2002. Theresults were quite satisfactory and reported as follows.

  14. Schwann Cells Transplantation Promoted and the Repair of Brain Stem Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    HONG WAN; YI-HUA AN; MEI-ZHEN SUN; YA-ZHUO ZHANG; ZHONG-CHENG WANG

    2003-01-01

    To explore the possibility of Schwann cells transplantation to promote the repair of injured brain stem reticular structure in rats. Methods Schwann cells originated from sciatic nerves of 1 to 2-day-old rats were expanded and labelled by BrdU in vitro, transplanted into rat brain stem reticular structure that was pre-injured by electric needle stimulus. Immunohistochemistry and myelin-staining were used to investigate the expression of BrdU, GAP-43 and new myelination respectively. Results BrdU positive cells could be identified for up to 8 months and their number increased by about 23%, which mainly migrated toward injured ipsilateral cortex. The GAP-43expression reached its peak in 1 month after transplantation and was significantly higher than that in the control group. New myelination could be seen in destructed brain stem areas. Conclusion The transplantation of Schwann cells can promote the restoration of injured brain stem reticular structure.

  15. Ketamine reduces the cell death following inflammatory pain in newborn rat brain.

    Science.gov (United States)

    Anand, Kanwaljeet J S; Garg, Sarita; Rovnaghi, Cynthia R; Narsinghani, Umesh; Bhutta, Adnan T; Hall, Richard W

    2007-09-01

    Premature infants experience untreated repetitive pain that may alter their brain development. Effects of ketamine and repetitive pain on cellular death and subsequent behavior were studied in neonatal rats. Rat pups were randomized to undisturbed controls (C), 4% formalin injection (F), ketamine alone (K, 5 mg/kg) or formalin plus ketamine (KF) and were assessed for neuroactivation with Fos protein, cellular death with FluoroJade-B, cognition with the radial arm maze, and pain thresholds with the hot-plate. Greater Fos expression and cell death occurred in F vs. C groups in defined brain areas at 1 and 4 h in F compared with other groups. Cell death was accentuated 3.3-fold in cortical areas and 1.6-fold in subcortical areas in the F compared with the C group following repetitive pain and sacrifice 18-20 h later. These effects were ameliorated by ketamine. Compared with the F group, all other groups demonstrated greater exploratory and rearing behaviors and decreased time for bait consumption at 1-h and 3-h intervals. Significantly greater thermal pain latencies occurred in the KF and F groups. Repetitive neonatal pain accentuates neuronal excitation and cell death in developmentally regulated cortical and subcortical areas, which decreases the acquisition of visual-spatial clues, short-term and long-term memory, and increases pain latencies. Ketamine analgesia mitigates most of these effects.

  16. Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression.

    Science.gov (United States)

    Behnan, Jinan; Isakson, Pauline; Joel, Mrinal; Cilio, Corrado; Langmoen, Iver A; Vik-Mo, Einar O; Badn, Wiaam

    2014-05-01

    The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal stem cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro and that the non-MSC population is nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic mice and GL261-GFP cells inoculated into wild-type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients.

  17. Possible role of brain stem respiratory neurons in mediating vomiting during space motion sickness

    Science.gov (United States)

    Miller, A. D.; Tan, L. K.

    1987-01-01

    The object of this study was to determine if brain stem expiratory neurons control abdominal muscle activity during vomiting. The activity of 27 ventral respiratory group expiratory neurons, which are known to be of primary importance for control of abdominal muscle activity during respiration, was recorded. It is concluded that abdominal muscle activity during vomiting must be controlled not only by some brain stem expiratory neurons but also by other input(s).

  18. The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course.

    Science.gov (United States)

    Schaefer, Jennifer E

    2016-01-01

    The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented.

  19. Dentate gyrus abnormalities in sudden unexplained death in infants: morphological marker of underlying brain vulnerability.

    Science.gov (United States)

    Kinney, Hannah C; Cryan, Jane B; Haynes, Robin L; Paterson, David S; Haas, Elisabeth A; Mena, Othon J; Minter, Megan; Journey, Kelley W; Trachtenberg, Felicia L; Goldstein, Richard D; Armstrong, Dawna D

    2015-01-01

    Sudden unexplained death in infants, including the sudden infant death syndrome, is likely due to heterogeneous causes that involve different intrinsic vulnerabilities and/or environmental factors. Neuropathologic research focuses upon the role of brain regions, particularly the brainstem, that regulate or modulate autonomic and respiratory control during sleep or transitions to waking. The hippocampus is a key component of the forebrain-limbic network that modulates autonomic/respiratory control via brainstem connections, but its role in sudden infant death has received little attention. We tested the hypothesis that a well-established marker of hippocampal pathology in temporal lobe epilepsy-focal granule cell bilamination in the dentate, a variant of granule cell dispersion-is associated with sudden unexplained death in infants. In a blinded study of hippocampal morphology in 153 infants with sudden and unexpected death autopsied in the San Diego County medical examiner's office, deaths were classified as unexplained or explained based upon autopsy and scene investigation. Focal granule cell bilamination was present in 41.2% (47/114) of the unexplained group compared to 7.7% (3/39) of the explained (control) group (p infants with sudden unexplained death may represent a developmental vulnerability that leads to autonomic/respiratory instability or autonomic seizures, and sleep-related death when the infants are challenged with homeostatic stressors. Importantly, these lesions can be recognized in microscopic sections prepared in current forensic practice. Future research is needed to determine the relationship between hippocampal and previously reported brainstem pathology in sudden infant death.

  20. Mediation of autophagic cell death by type 3 ryanodine receptor (RyR3 in adult hippocampal neural stem cells

    Directory of Open Access Journals (Sweden)

    Kyung Min eChung

    2016-05-01

    Full Text Available Cytoplasmic Ca2+ actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca2+ levels is observed in various neuropathological states including Alzheimer’s and Parkinson’s diseases. Ryanodine receptors (RyRs and IP3 receptors (IP3Rs, the main Ca2+ release channels located in endoplasmic reticulum (ER membranes, are known to direct various cellular events such as autophagy and apoptosis. Here we investigated the intracellular Ca2+-mediated regulation of survival and death of adult hippocampal neural stem (HCN cells utilizing an insulin withdrawal model of autophagic cell death. Despite comparable expression levels of RyR and IP3R transcripts in HCN cells at normal state, the expression levels of RyRs — especially RyR3 — were markedly upregulated upon insulin withdrawal. While treatment with the RyR agonist caffeine significantly promoted the autophagic death of insulin-deficient HCN cells, treatment with its inhibitor dantrolene prevented the induction of autophagy following insulin withdrawal. Furthermore, CRISPR/Cas9-mediated knockout of the RyR3 gene abolished autophagic cell death of HCN cells. This study delineates a distinct, RyR3-mediated ER Ca2+ regulation of autophagy and programmed cell death in neural stem cells. Our findings provide novel insights into the critical, yet understudied mechanisms underlying the regulatory function of ER Ca2+ in neural stem cell biology.

  1. Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease?

    Institute of Scientific and Technical Information of China (English)

    Hyung Ho Yoon; Joongkee Min; Nari Shin; Yong Hwan Kim; Jin-Mo Kim; Yu-Shik Hwang; Jun-Kyo Francis Suh; Onyou Hwang; Sang Ryong Jeon

    2013-01-01

    Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18 F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.

  2. Isolation, cultivation and identification of brain glioma stem cells by magnetic bead sorting

    Institute of Scientific and Technical Information of China (English)

    Xiuping Zhou; Chao Zheng; Qiong Shi; Xiang Li; Zhigang Shen; Rutong Yu

    2012-01-01

    This study describes a detailed process for obtaining brain glioma stem cells from freshly dissected human brain glioma samples using an immunomagnetic bead technique combined with serum-free media pressure screening. Furthermore, the proliferation, differentiation and self-renewal biological features of brain glioma stem cells were identified. Results showed that a small number of CD133 positive tumor cells isolated from brain glioma samples survived as a cell suspension in serum-free media and proliferated. Subcultured CD133 positive cells maintained a potent self-renewal and proliferative ability, and expressed the stem cell-specific markers CD133 and nestin. After incubation with fetal bovine serum, the number of glial fibrillary acidic protein and microtubule associated protein 2 positive cells increased significantly, indicating that the cultured brain glioma stem cells can differentiate into astrocytes and neurons. Western blot analysis showed that tumor suppressor phosphatase and tensin homolog was highly expressed in tumor spheres compared with the differentiated tumor cells. These experimental findings indicate that the immunomagnetic beads technique is a useful method to obtain brain glioma stem cells from human brain tumors.

  3. The prolongation of somatic support in a pregnant woman with brain-death: a case report

    Directory of Open Access Journals (Sweden)

    Amaral Eliana

    2006-04-01

    Full Text Available Abstract Background Medical literature has increasingly reported cases of maternal brain death during pregnancy. This is a rare situation which demands the decision and, depending on the gestational age, the implementation of a set of measures to prolong the homeostasis of the human body after brain death for the purpose of maintaining the foetus alive until its viability. Case presentation A 40 year old woman suffered an intracranial haemorrhage during the 25th week of pregnancy. Despite neurosurgical drainage of a gross intraparenchymatous haematoma, the patient developed brain death. Upon confirmation of this diagnosis, she received full ventilatory and nutritional support, vasoactive drugs, maintenance of normothermia, hormone replacement and other supportive measures required to prolong gestation and improve the survival prognosis of her foetus. All decisions regarding the patient's treatment were taken in consensus with her family. She also received corticosteroids to accelerate foetal lung maturity. During the twenty-five days of somatic support, the woman's condition remained stable; however, during the last seven days the foetus developed oligohydramnios and brain-sparring, which led the medical team to take the decision to perform a Caesarean section at that moment. After delivery, the patient's organs were removed for donation. The male infant was born weighing 815 g, with an Apgar score of 9 and 10 at the first and fifth minutes, respectively. The infant was admitted to the neonatal intensive care unit, but did not require mechanical ventilation and had no major complications. He was discharged at 40 days of life, with no sequelae and weighing 1850 g. Conclusion These results are in accordance with findings from previous studies and case reports suggesting the appropriateness and safety of extended somatic support during pregnancy under certain circumstances. They also suggest the need for prompt diagnosis of brain death before the

  4. Massive cerebral fat embolism leading to brain death: A rare presentation

    Directory of Open Access Journals (Sweden)

    Richa Aggarwal

    2015-01-01

    Full Text Available Fat embolism syndrome (FES typically consists of a triad of neurological, pulmonary, and cutaneous symptoms. There exist few case reports of FES involving central nervous system (CNS only without pulmonary involvement. In most of such cases, CNS involvement is partial, and patients recover fully neurologically within days. We report a rare and unusual case of massive cerebral fat embolism that led to brain death in trauma patient.

  5. Apnea test in the determination of brain death in patients treated with extracorporeal membrane oxygenation (ECMO).

    Science.gov (United States)

    Saucha, Wojciech; Sołek-Pastuszka, Joanna; Bohatyrewicz, Romuald; Knapik, Piotr

    2015-01-01

    Extracorporeal Membrane Oxygenation (ECMO) is a well-established method of support in patients with severe respiratory and/or circulatory failure. Unfortunately, this invasive method of treatment is associated with a high risk of neurological complications including brain death. Proper diagnosis of brain death is crucial for the termination of futile medical care. Currently, the legal system in Poland does not provide an accepted protocol for apnea tests for patients on ECMO support. Veno-arterial ECMO is particularly problematic in this regard because it provides both gas exchange and circulatory support. CO₂ elimination by ECMO prevents hypercapnia, which is required to perform an apnea test. Several authors have described a safe apnea test procedure in patients on ECMO. Maximal reduction of the sweep gas flow to the oxygenator should maintain an acceptable haemoglobin oxygenation level and reduce elimination of carbon dioxide. Hypercapnia achieved via this method should allow an apnea test to be conducted in the typical manner. In the case of profound desaturation and an inadequate increase in the arterial CO₂ concentration, the sweep gas flow rate may be increased to obtain the desired oxygenation level, and exogenous carbon dioxide may be added to achieve a target carbon dioxide level. Incorporation of an apnea test for ECMO patients is planned in the next edition of the Polish guidelines on the determination of brain death.

  6. Complications associated with the apnea test in the determination of the brain death

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-liang; FANG Qiang; LI Li; QIU Yun-qing; LUO Ben-yan

    2008-01-01

    Background An apnea test is essentialin the clinical determination of brain death.This study was conducted to analyse complications associated with the apnea test in the determination of the brain death.Methods On 93 adult patients In coma in Zhejiang Province of China from January 2003 to December 2006,179 apnea tests were performed as a part of the determination of brain death.Potential risk conditions and complications were analysed during apnea tests.Results During apnea,sedous cardiac arrhythmia did not occur in all patients.Complications occurred in 37 of 179 (21%)apnea tests.Hypotension occurred in 30 patients(17%)and it was obsewed in 8/94(9%)tests with baseline value of systolic arterial blood pressure not less than 120 mmHg,and 22/85(26%)lass than 120 mmHg(P<0.05).Severe hypoxaemia occurred in 10 patients(6%)of which 3/138(2%)tests with baseline value of arterial oxygen pressure not less than 200 mmHg,and 7/41(17%)less than 200 mmHg(P<0.05).Conclusions This study demonstrated that complications occurred mostly in patients with inadequate baseline systolic arterial blood pressure and preoxygenation.Adequate precautions during the apnea tests may reduce the risk of cardiovascular and oxygenation complication.

  7. Latin American consensus on the use of transcranial Doppler in the diagnosis of brain death.

    Science.gov (United States)

    2014-01-01

    Transcranial Doppler evaluates cerebral hemodynamics in patients with brain injury and is a useful technical tool in diagnosing cerebral circulatory arrest, usually present in the brain-dead patient. This Latin American Consensus was formed by a group of 26 physicians experienced in the use of transcranial Doppler in the context of brain death. The purpose of this agreement was to make recommendations regarding the indications, technique, and interpretation of the study of transcranial ultrasonography in patients with a clinical diagnosis of brain death or in the patient whose clinical diagnosis presents difficulties; a working group was formed to enable further knowledge and to strengthen ties between Latin American physicians working on the same topic. A review of the literature, concepts,and experiences were exchanged in two meetings and via the Internet. Questions about pathophysiology, equipment, techniques, findings, common problems, and the interpretation of transcranial Doppler in the context of brain death were answered. The basic consensus statements are the following: cerebral circulatory arrest is the final stage in the evolution of progressive intracranial hypertension, which is visualized with transcranial Doppler as a "pattern of cerebral circulatory arrest". The following are accepted as the standard of cerebral circulatory arrest: reverberant pattern, systolic spikes, and absence of previously demonstrated flow. Ultrasonography should be used - in acceptable hemodynamic conditions - in the anterior circulation bilaterally (middle cerebral artery) and in the posterior (basilar artery) territory. If no ultrasonographic images are found in any or all of these vessels, their proximal arteries are acceptable to be studied to look for a a pattern of cerebral circulatory arrest.

  8. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development

    Directory of Open Access Journals (Sweden)

    Bello Bruno C

    2008-02-01

    Full Text Available Abstract Background In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Results Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Conclusion Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.

  9. Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain.

    Directory of Open Access Journals (Sweden)

    Montserrat C Anguera

    2011-09-01

    Full Text Available The Tsx gene resides at the X-inactivation center and is thought to encode a protein expressed in testis, but its function has remained mysterious. Given its proximity to noncoding genes that regulate X-inactivation, here we characterize Tsx and determine its function in mice. We find that Tsx is actually noncoding and the long transcript is expressed robustly in meiotic germ cells, embryonic stem cells, and brain. Targeted deletion of Tsx generates viable offspring and X-inactivation is only mildly affected in embryonic stem cells. However, mutant embryonic stem cells are severely growth-retarded, differentiate poorly, and show elevated cell death. Furthermore, male mice have smaller testes resulting from pachytene-specific apoptosis and a maternal-specific effect results in slightly smaller litters. Intriguingly, male mice lacking Tsx are less fearful and have measurably enhanced hippocampal short-term memory. Combined, our study indicates that Tsx performs general functions in multiple cell types and links the noncoding locus to stem and germ cell development, learning, and behavior in mammals.

  10. Stem cells modified by brain-derived neurotrophic fac-tor to promote stem cells differentiation into neurons and enhance neuromotor function after brain injury

    Institute of Scientific and Technical Information of China (English)

    ZHANG Sai; LIU Xiao-zhi; LIU Zhen-lin; WANG Yan-min; HU Qun-liang; MA Tie-zhu; SUN Shi-zhong

    2009-01-01

    Objective: To promote stem cells differentiation into neurons and enhance neuromotor function after brain in-jury through brain-derived neurotrophic factor (BDNF) induction.Methods: Recombinant adenovirus vector was ap-plied to the transfection of BDNF into human-derived um-bilical cord mesenchymal stem cells (UCMSCs). Enzyme linked immunosorbent assay (ELISA) was used to deter-mine the secretion phase of BDNF. The brain injury model of athymic mice induced by hydraulic pressure percussion was established for transplantation of stem cells into the edge of injury site. Nerve function scores were obtained, and the expression level of transfected and non-transfected BDNF, proportion of neuron specific enolase (NSE) andglial fibrillary acidic protein (GFAP), and the number of apoptosis cells were compared respectively. Results: The BDNF expression achieved its stabiliza-tion at a high level 72 hours after gene transfection. The mouse obtained a better score of nerve function, and the proportion of the NSE-positive cells increased significantly (P<0.05), but GFAP-positive cells decreased in BDNF-UCMSCs group compared with the other two groups (P<0.05). At the site of high expression of BDNF, the number of apoptosis cells decreased markedly.Conclusion: BDNF gene can promote the differentia-tion of the stem cells into neurons rather than gliai cells, and enhance neuromotor function after brain injury.

  11. Prospects and Limitations of Using Endogenous Neural Stem Cells for Brain Regeneration

    Directory of Open Access Journals (Sweden)

    Kazunobu Sawamoto

    2011-01-01

    Full Text Available Neural stem cells (NSCs are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunological, and ethical problems. Recent studies have revealed that NSCs also reside in the adult brain. The endogenous NSCs are activated in response to disease or trauma, and produce new neurons and glia, suggesting they have the potential to regenerate damaged brain tissue while avoiding the above-mentioned problems. Here we present an overview of the possibility and limitations of using endogenous NSCs in regenerative medicine.

  12. Prospects and limitations of using endogenous neural stem cells for brain regeneration.

    Science.gov (United States)

    Kaneko, Naoko; Kako, Eisuke; Sawamoto, Kazunobu

    2011-01-14

    Neural stem cells (NSCs) are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunological, and ethical problems. Recent studies have revealed that NSCs also reside in the adult brain. The endogenous NSCs are activated in response to disease or trauma, and produce new neurons and glia, suggesting they have the potential to regenerate damaged brain tissue while avoiding the above-mentioned problems. Here we present an overview of the possibility and limitations of using endogenous NSCs in regenerative medicine.

  13. Amelioration of renal damage by administration of anti-thymocyte globulin to potential donors in a brain death rat model.

    Science.gov (United States)

    Cicora, F; Stringa, P; Guerrieri, D; Roberti, J; Ambrosi, N; Toniolo, F; Cicora, P; Palti, G; Vásquez, D; Raimondi, C

    2012-09-01

    Brain death (BD), a non-immunological factor of renal injury, triggers an inflammatory process causing pathological signs of cell death in the kidney, such as necrosis and apoptosis. Kidneys from brain dead donors show lower success rates than kidneys from living donors and one strategy to improve transplantation outcome is to precondition the donors. For the first time, anti-rat thymoglobulin (rATG) was administered in an experimental brain death animal model to evaluate if it could ameliorate histopathological damage and improve organ function. Animals were divided into three groups: V (n=5) ventilated for 2h; BD (n=5) brain death and ventilated for 2h; and BD+rATG (n=5) brain death, ventilated for 2h, rATG was administered during brain death (10mg/kg). We observed lower creatinine levels in treatment groups (means): V, 0·88±0·22 mg/dl; BD, 1·37±0·07 mg/dl; and BD+rATG, 0·64±0·02 mg/dl (BD versus BD+rATG, Pbrain death setting (V: 32±7·5 versus BD: 129±18). Findings suggest that rATG administered to potential donors may ameliorate renal damage caused by BD. These findings could contribute in the search for specific cytoprotective interventions to improve the quality and viability of transplanted organs.

  14. Origins and clinical implications of the brain tumor stem cell hypothesis

    OpenAIRE

    2009-01-01

    With the advent of the cancer stem cell hypothesis, the field of cancer research has experienced a revolution in how we think of and approach cancer. The discovery of “brain tumor stem cells” has offered an explanation for several long-standing conundrums on why brain tumors behave the way they do to treatment. Despite the great amount of research that has been done in order to understand the molecular aspects of malignant gliomas, the prognosis of brain tumors remains dismal. The slow progre...

  15. Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro.

    Science.gov (United States)

    Aleksandrova, M A; Poltavtseva, R A; Marei, M V; Sukhikh, G T

    2016-05-01

    Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.

  16. Motricidade reflexa na morte cerebral The reflex activity in the brain death

    Directory of Open Access Journals (Sweden)

    Wilson L. Sanvito

    1972-03-01

    Full Text Available O diagnóstico de morte cerebral está baseado em critérios clínicos, eletrencefalográficos e angiográficos. Do ponto de vista clínico deve ser evidenciado o seguinte quadro: coma profundo, midríase paralítica bilateral, ausência de reação a qualquer estímulo externo, apnéia, arreflexia superficial e profunda. Do ponto de vista eletrencefalográfico são necessários dois registros, separados por um intervalo de 24 horas, evidenciando traçados iselétricos. No presente trabalho são estudados 15 pacientes com morte cerebral comprovada do ponto de vista clínico e eletrencefalográfico. Em 8 pacientes havia persistência de atividade reflexa durante a fase de morte cerebral (reflexos profundos e/ou superficiais. Fenômenos de automatismos medulares também foram verificados em 3 pacientes.The diagnosis of brain death is based in clinical, electroencephalographic and angiographic data. The criteria for diagnosis of brain death are: deep coma with unreceptivity and unresponsiveness, no movements or breathing (the patient's respiration must be maintained artificially, bilateral dilated and fixed pupils, absence of corneal reflexes, no response to caloric test, absence of deep tendon reflexes and of the superficial abdominal and plantar reflexes, isoelectric EEG maintained for twenty-four hours. The purpose of this study was to observe the natural clinical courses of 15 patients with brain death, specially the data concerning the deep and superficial reflexes. From 15 patients fulfilling the criteria of brain death, 8 maintained spinal reflexes up to the time of cardiac arrest; in five of these patients the superficial abdominal reflexes were present and the reflexes of spinal automatism could be elicited. These results show that the absence of deep and superficial reflexes can't be considered as essencial for the diagnosis of brain death.

  17. Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation

    OpenAIRE

    Hrydziuszko, Olga; Perera, M. Thamara P. R; Laing, Richard; Kirwan, Jennifer; Silva, Michael A; Richards, Douglas A.; Murphy, Nick; Mirza, Darius F; Viant, Mark R.

    2016-01-01

    Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27...

  18. Expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats, and to observe the temporal patterns of its expressions following percussion.METHODS: Male Sprague-Dawley rats were divided into normal control, sham operation control and injury groups. The rats of injury group subjected to moderate lateral fluid percussion injury (0.2 mPa), and then were subdivided into 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h and 12 h groups according to the time elapsed after injury. The expression of c-jun was studied by immunohistochemistry and in situ hybridization. RESULTS: After percussion for 15 min, Jun positive neurons increased in brain stem progressively, and peaked at 12h. At 5min after percussion, the induction of c-jun mRNA was increased, and remained elevated up to 1h-2h after brain injury. CONCLUSION: The induction and expression of the c-jun in brain stem after fluid percussion brain injury were increased rapidly and lasted for a long time.

  19. PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation.

    Science.gov (United States)

    Trapp, Stefan; Cork, Simon C

    2015-10-15

    Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation.

  20. Mesenteric hypoperfusion and inflammation induced by brain death are not affected by inhibition of the autonomic storm in rats

    OpenAIRE

    Rafael Simas; Ferreira,Sueli G.; Laura Menegat; Zanoni,Fernando L.; Cristiano J. Correia; Silva, Isaac A; Paulina Sannomiya; Moreira,Luiz F.P.

    2015-01-01

    OBJECTIVES: Brain death is typically followed by autonomic changes that lead to hemodynamic instability, which is likely associated with microcirculatory dysfunction and inflammation. We evaluated the role of the microcirculation in the hemodynamic and inflammatory events that occur after brain death and the effects of autonomic storm inhibition via thoracic epidural blockade on mesenteric microcirculatory changes and inflammatory responses. METHODS: Male Wistar rats were anesthetized and me...

  1. Redefining Death

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The results of 20 years of research on brain death will be released to the public, the Chinese Ministry of Health reported in early April. A special ministry team has drafted the criteria for brain death in Criteria for the Diagnosis of Brain Death in Adults (Revised Edition) and Technical Specifications for the Diagnosis

  2.  Liver transplantation in the critically ill: donation after cardiac death compared to donation after brain death grafts.

    Science.gov (United States)

    Taner, C Burcin; Bulatao, Ilynn G; Arasi, Lisa C; Perry, Dana K; Willingham, Darrin L; Sibulesky, Lena; Rosser, Barry G; Canabal, Juan M; Nguyen, Justin H; Kramer, David J

    2012-01-01

     Patients with end stage liver disease may become critically ill prior to LT requiring admission to the intensive care unit (ICU). The high acuity patients may be thought too ill to transplant; however, often LT is the only therapeutic option. Choosing the correct liver allograft for these patients is often difficult and it is imperative that the allograft work immediately. Donation after cardiac death (DCD) donors provide an important source of livers, however, DCD graft allocation remains a controversial topic, in critically ill patients. Between January 2003-December 2008, 1215 LTs were performed: 85 patients at the time of LT were in the ICU. Twelve patients received DCD grafts and 73 received donation after brain dead (DBD) grafts. After retransplant cases and multiorgan transplants were excluded, 8 recipients of DCD grafts and 42 recipients of DBD grafts were included in this study. Post-transplant outcomes of DCD and DBD liver grafts were compared. While there were differences in graft and survival between DCD and DBD groups at 4 month and 1 year time points, the differences did not reach statistical significance. The graft and patient survival rates were similar among the groups at 3-year time point. There is need for other large liver transplant programs to report their outcomes using liver grafts from DCD and DBD donors. We believe that the experience of the surgical, medical and critical care team is important for successfully using DCD grafts for critically ill patients.

  3. Stem cell therapy for neonatal brain injury : Perspectives and Challenges

    NARCIS (Netherlands)

    Titomanlio, Luigi; Kavelaars, Annemieke; Dalous, Jeremie; Mani, Shyamala; El Ghouzzi, Vincent; Heijnen, Cobi; Baud, Olivier; Gressens, Pierre

    2011-01-01

    Cerebral palsy is a major health problem caused by brain damage during pregnancy, delivery, or the immediate postnatal period. Perinatal stroke, intraventricular hemorrhage, and asphyxia are the most common causes of neonatal brain damage. Periventricular white matter damage (periventricular leukoma

  4. Spinal shock and brain death': somatic pathophysiological equivalence and implications for the integrative-unity rationale.

    Science.gov (United States)

    Shewmon, D A

    1999-05-01

    The somatic pathophysiology of high spinal cord injury (SCI) not only is of interest in itself but also sheds light on one of the several rationales proposed for equating 'brain death' (BD) with death, namely that the brain confers integrative unity upon the body, which would otherwise constitute a mere conglomeration of cells and tissues. Insofar as the neuropathology of BD includes infarction down to the foramen magnum, the somatic pathophysiology of BD should resemble that of cervico-medullary junction transection plus vagotomy. The endocrinologic aspects can be made comparable either by focusing on BD patients without diabetes insipidus or by supposing the victim of high SCI to have pre-existing therapeutically compensated diabetes insipidus. The respective literatures on intensive care for BD organ donors and high SCI corroborate that the two conditions are somatically virtually identical. If SCI victims are alive at the level of the 'organism as a whole', then so must be BD patients (the only significant difference being consciousness). Comparison with SCI leads to the conclusion that if BD is to be equated with death, a more coherent reason must be adduced than that the body as a biological organism is dead.

  5. Problems associated with the apnea test in the diagnosis of brain death

    Directory of Open Access Journals (Sweden)

    Saposnik Gustavo

    2004-07-01

    Full Text Available Background: Brain death is the absence of all cortical functions, including the brainstem. The apnea test (AT is a necessary requisite to complete this diagnosis. Anecdotal reports describing hypotension and acidosis due to apnea test have been reported. However, there are few studies that evaluate complications or difficulties related to this procedure. Objective: To analyze medical problems associated with the apnea test. Methods and Patients: We analyzed clinical features, potential risk conditions, and problems in 129 brain dead patients during the apnea test. The diagnosis of brain death was made according to the American Academy of Neurology recommendations. Results: Clinical problems during the apnea test were detected in more than two thirds of patients, including: arterial hypotension (12%, acidosis (68%, and hypoxemia (23%. Four patients developed major complications, including: pneumothorax, cardiac arrest, bradycardia, atrial fibrillation and myocardial infarction. Conclusion: The apnea test is not an innocuous procedure. Complications during the AT are more common than reported and limit organ procurement for transplantation. Guidelines for performing the AT should be followed in order to avoid clinical complications.

  6. [Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

    Science.gov (United States)

    Aleksandrova, M A; Marey, M V

    2015-01-01

    Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

  7. Mesenchymal Stem Cells Expressing Brain-Derived Neurotrophic Factor Enhance Endogenous Neurogenesis in an Ischemic Stroke Model

    Directory of Open Access Journals (Sweden)

    Chang Hyun Jeong

    2014-01-01

    Full Text Available Numerous studies have reported that mesenchymal stem cells (MSCs can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs, we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF gene via adenoviral transduction mediated by cell-permeable peptides and investigated whether BDNF-modified hBM-MSCs (MSCs-BDNF contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO. Transplantation of MSCs induced the proliferation of 5-bromo-2′-deoxyuridine (BrdU- positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX- positive neuroblasts and Neuronal Nuclei (NeuN- positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis.

  8. Mesenchymal stem cells expressing brain-derived neurotrophic factor enhance endogenous neurogenesis in an ischemic stroke model.

    Science.gov (United States)

    Jeong, Chang Hyun; Kim, Seong Muk; Lim, Jung Yeon; Ryu, Chung Heon; Jun, Jin Ae; Jeun, Sin-Soo

    2014-01-01

    Numerous studies have reported that mesenchymal stem cells (MSCs) can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs), we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF) gene via adenoviral transduction mediated by cell-permeable peptides and investigated whether BDNF-modified hBM-MSCs (MSCs-BDNF) contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO). Transplantation of MSCs induced the proliferation of 5-bromo-2'-deoxyuridine (BrdU-) positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX-) positive neuroblasts and Neuronal Nuclei (NeuN-) positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS) or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis.

  9. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Fatemeh Anbari; Mohammad Ali Khalili; Ahmad Reza Bahrami; Arezoo Khoradmehr; Fatemeh Sadeghian; Farzaneh Fesahat; Ali Nabi

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intrave-nous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and ad-ministered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significant-ly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells.

  10. Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate.

    Science.gov (United States)

    Tovar-y-Romo, Luis B; Penagos-Puig, Andrés; Ramírez-Jarquín, Josué O

    2016-01-01

    Neuronal survival depends on multiple factors that comprise a well-fueled energy metabolism, trophic input, clearance of toxic substances, appropriate redox environment, integrity of blood-brain barrier, suppression of programmed cell death pathways and cell cycle arrest. Disturbances of brain homeostasis lead to acute or chronic alterations that might ultimately cause neuronal death with consequent impairment of neurological function. Although we understand most of these processes well when they occur independently from one another, we still lack a clear grasp of the concerted cellular and molecular mechanisms activated upon neuronal damage that intervene in protecting damaged neurons from death. In this review, we summarize a handful of endogenously activated mechanisms that balance molecular cues so as to determine whether neurons recover from injury or die. We center our discussion on mechanisms that have been identified to participate in stroke, although we consider different scenarios of chronic neurodegeneration as well. We discuss two central processes that are involved in endogenous repair and that, when not regulated, could lead to tissue damage, namely, trophic support and neuroinflammation. We emphasize the need to construct integrated models of neuronal degeneration and survival that, in the end, converge in neuronal fate after injury. Under neurodegenerative conditions, endogenously activated mechanisms balance out molecular cues that determine whether neurons contend toxicity or die. Many processes involved in endogenous repair may as well lead to tissue damage depending on the strength of stimuli. Signaling mediated by trophic factors and neuroinflammation are examples of these processes as they regulate different mechanisms that mediate neuronal demise including necrosis, apoptosis, necroptosis, pyroptosis and autophagy. In this review, we discuss recent findings on balanced regulation and their involvement in neuronal death.

  11. Transcriptional profiling of adult neural stem-like cells from the human brain.

    Science.gov (United States)

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  12. Control of abdominal muscles by brain stem respiratory neurons in the cat

    Science.gov (United States)

    Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

    1985-01-01

    The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

  13. Anencefalia e morte cerebral (neurológica Anencephaly and brain death

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    Maria Lúcia Fernandes Penna

    2005-06-01

    Full Text Available Vem-se discutindo no país a ética da interrupção da gravidez no caso de fetos anencéfalos. Os opositores ao aborto nesses casos apontam, entre outros argumentos, que não se trata de morte cerebral devido à presença de tronco encefálico. Neste artigo discutimos o conceito de morte cerebral e sua aplicação no que tange à anencefalia. Apontamos alguns aspectos históricos do desenvolvimento desse conceito e a importância de ser considerada a diferença entre conceito e critérios. A morte neurológica é a perda definitiva e total da consciência, enquanto a presença do tronco cerebral é apenas um critério a ser usado nos casos de lesão encefálica em encéfalos antes perfeitos. O conceito de morte cerebral se aplica completamente à ausência de córtex dos anencéfalos, o que sem dúvida permite sua retirada do útero materno. Manter juridicamente a criminalização desse procedimento é uma interferência religiosa no Estado laico e democrático, que impede o exercício de escolha pelos indivíduos segundo seu credo.Brazilian society has recently discussed the ethics of interrupting pregnancy in the case of an anencephalic fetus. In such cases, anti-abortionists contend that anencephaly is not the same as brain death, since a brainstem is present. This article discusses the concept of brain death and its application to the issue of anencephaly. We point to key historical aspects in the development of this concept and the importance of considering the difference between concept and criteria. Neurological death is the definitive and complete loss of consciousness, while the presence of a brainstem is merely a criterion to be used in cases of head injury in previously intact brains. The concept of brain death is totally applicable to the absence of cortex in a fetus with anencephaly, which without a doubt allows such a fetus to be removed from the uterus. To maintain the criminalization of this procedure by legal means represents

  14. Organ donation after brain death in India: A trained intensivist is the key to success

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    Vijayanand Palaniswamy

    2016-01-01

    Full Text Available Organ donation after brain death in India is gaining momentum but only in a few states. Tamil Nadu is leading in the country in this regard. Certain cities have performed well compared to Chennai′s results. A single tertiary hospital performed 28 donations in a 17 months period with a team of an intensivist and a transplant coordinator. An intensivist needs training and interest in this noble cause. There is no formal training program in this noble cause for doctors in India. A structured formal training needs to be introduced and made mandatory for the doctors in intensive care to make this donation process a successful program.

  15. Patient-derived stem cells: pathways to drug discovery for brain diseases

    Directory of Open Access Journals (Sweden)

    Alan eMackay-Sim

    2013-03-01

    Full Text Available The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS. The second is patient-derived stem cells for modelling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprogramming of somatic cells into induced pluripotent stem cells (iPSCs. There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson’s disease. Some genetic diseases are also modelled in embryonic stem cells generated from blastocysts rejected during in vitro fertilisation. Neural stem cells have been isolated from post-mortem brain of Alzheimer’s patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson’s disease. High content screening is already in use to find small molecules for the generation and differentiation of embryonic stem cells and induced pluripotent stem cells. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for high

  16. Furan fatty acids efficiently rescue brain cells from cell death induced by oxidative stress.

    Science.gov (United States)

    Teixeira, Antoinette; Cox, Ruud C; Egmond, Maarten R

    2013-08-01

    Treatment of rat brain C6 astroglioma cells with furan fatty acid F6 prior to exposure to hydrogen peroxide shows a strong protective effect of F6 against cell death resulting from oxidative stress. This protective effect is obtained only for F6 administered as a free fatty acid and with an intact furan ring. It is proposed that brain cells are rescued by F6 scavenging radicals elicited by lipid peroxidation within the cell membrane. Oxidative processes outside the cell membrane, such as protein carbonylation, are not affected by F6. Furan fatty acids such as those present in fish oils and marine organisms are likely beneficial for consumption in reducing the risk of diseases that have been implicated to arise from oxidative stress, such as Alzheimer's disease.

  17. Correlation of auditory brain stem response and the MRI measurements in neuro-degenerative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Hidekazu (Tokyo Women' s Medical Coll. (Japan))

    1989-06-01

    The purpose of this study is to elucidate correlations of several MRI measurements of the cranium and brain, functioning as a volume conductor, to the auditory brain stem response (ABR) in neuro-degenerative disorders. The subjects included forty-seven patients with spinocerebellar degeneration (SCD) and sixteen of amyotrophic lateral sclerosis (ALS). Statistically significant positive correlations were found between I-V and III-V interpeak latencies (IPLs) and the area of cranium and brain in the longitudinal section of SCD patients, and between I-III and III-V IPLs and the area in the longitudinal section of those with ALS. And, also there were statistically significant correlations between the amplitude of the V wave and the area of brain stem as well as that of the cranium in the longitudinal section of SCD patients, and between the amplitude of the V wave and the area of the cerebrum in the longitudinal section of ALS. In conclusion, in the ABR, the IPLs were prolonged and the amplitude of the V wave was decreased while the MRI size of the cranium and brain increased. When the ABR is applied to neuro-degenerative disorders, it might be important to consider not only the conduction of the auditory tracts in the brain stem, but also the correlations of the size of the cranium and brain which act as a volume conductor. (author).

  18. Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.

    Science.gov (United States)

    Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Vemuri, Mohan C

    2013-11-01

    Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

  19. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

    Directory of Open Access Journals (Sweden)

    Ninette Amariglio

    2009-02-01

    Full Text Available BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

  20. How stem cells speak with host immune cells in inflammatory brain diseases.

    Science.gov (United States)

    Pluchino, Stefano; Cossetti, Chiara

    2013-09-01

    Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

  1. End-of-life and brain death in acute coma and disorders of consciousness.

    Science.gov (United States)

    Greer, David M; Curiale, Gioacchino G

    2013-04-01

    Consulting neurologists are often asked to evaluate patients in acute nontraumatic coma. The authors review prognostication of functional outcomes, determining brain death, and managing end-of-life care. Prognostication of outcome after cardiac arrest in comatose patients is a frequently encountered scenario with high-stakes implications. However, current guidelines are limited by a failure to address the use of therapeutic hypothermia and thus may lead to overly pessimistic outcome prediction. Pupillary light responses and corneal reflexes remain highly predictive clinical signs of a poor prognosis. Motor responses have a high false-positive rate for predicting a poor outcome, especially in patients treated with therapeutic hypothermia. Ancillary testing with electroencephalography, somatosensory evoked potentials, serum neuron-specific enolase, and neuroimaging is often useful in predicting outcomes. Brain death is a clinical condition of irreversible coma of known cause with absent brainstem reflexes and apnea. An understanding of the value of confirmatory testing and the potential for confounding factors is essential in making a correct diagnosis. As coma carries a high mortality rate, neurologists must be capable of guiding goals of care, discussing end-of-life issues, and understanding organ-procurement procedures.

  2. Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells.

    Science.gov (United States)

    Spéder, Pauline; Brand, Andrea H

    2014-08-11

    Neural stem cells in the adult brain exist primarily in a quiescent state but are reactivated in response to changing physiological conditions. How do stem cells sense and respond to metabolic changes? In the Drosophila CNS, quiescent neural stem cells are reactivated synchronously in response to a nutritional stimulus. Feeding triggers insulin production by blood-brain barrier glial cells, activating the insulin/insulin-like growth factor pathway in underlying neural stem cells and stimulating their growth and proliferation. Here we show that gap junctions in the blood-brain barrier glia mediate the influence of metabolic changes on stem cell behavior, enabling glia to respond to nutritional signals and reactivate quiescent stem cells. We propose that gap junctions in the blood-brain barrier are required to translate metabolic signals into synchronized calcium pulses and insulin secretion.

  3. Transgenic over-expression of slit2 enhances disruption of blood-brain barrier and increases cell death after traumatic brain injury in mice.

    Science.gov (United States)

    Li, Shuai; Li, Hang; He, Xiao-Fei; Li, Ge; Zhang, Qun; Liang, Feng-Ying; Jia, Huan-Huan; Li, Jiang-Chao; Huang, Ren; Pei, Zhong; Wang, Li-Jing; Zhang, Yu

    2016-09-19

    Traumatic brain injury (TBI) is the leading cause of mortality and disability among male adolescents and young adults; and mild traumatic brain injury is the most common type of traumatic brain injury. The disruption of blood-brain barrier (BBB) plays an important role in brain trauma. Previously, we have found that slit2, a member of slit protein family, increases permeability of BBB. In the present study, we examined the role of slit2 in the pathogenesis of mild TBI in a mouse model of micro TBI. Rhodamine BandPI (PropidiumIodide) staining were used to detect the permeability of BBB and cell death, respectively. The leakage of Rhodamine B and cell death were significantly increased in Slit2-Tg mice than in C57 control mice after micro TBI. The present results suggest that over expression of slit2 plays a detrimental role in the pathophysiology of mild TBI.

  4. Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, Brandon M.; Leix, Kyle Alexander [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ji, Yajing [Department of Biomedical Science and Medicine, Michigan State University, East Lansing, MI 48824 (United States); Glaves, Richard Samuel Elliot [Department of Biology, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ash, David E. [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Mohanty, Dillip K., E-mail: Mohan1dk@cmich.edu [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States)

    2014-07-18

    Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well.

  5. Physics strategies for sparing neural stem cells during whole-brain radiation treatments

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J. [Department of Radiation Oncology, University of California San Francisco, San Francisco, California 94143-1708 (United States)

    2011-10-15

    Purpose: Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Methods: Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. Results: The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Conclusions: Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  6. Nuclear trafficking of Pten after brain injury leads to neuron survival not death.

    Science.gov (United States)

    Goh, Choo-Peng; Putz, Ulrich; Howitt, Jason; Low, Ley-Hian; Gunnersen, Jenny; Bye, Nicole; Morganti-Kossmann, Cristina; Tan, Seong-Seng

    2014-02-01

    There is controversy whether accumulation of the tumor suppressor PTEN protein in the cell nucleus under stress conditions such as trauma and stroke causes cell death. A number of in vitro studies have reported enhanced apoptosis in neurons possessing nuclear PTEN, with the interpretation that its nuclear phosphatase activity leads to reduction of the survival protein phospho-Akt. However, there have been no in vivo studies to show that nuclear PTEN in neurons under stress is detrimental. Using a mouse model of injury, we demonstrate here that brain trauma altered the nucleo-cytoplasmic distribution of Pten, resulting in increased nuclear Pten but only in surviving neurons near the lesion. This event was driven by Ndfip1, an adaptor and activator of protein ubiquitination by Nedd4 E3 ligases. Neurons next to the lesion with nuclear PTEN were invariably negative for TUNEL, a marker for cell death. These neurons also showed increased Ndfip1 which we previously showed to be associated with neuron survival. Biochemical assays revealed that overall levels of Pten in the affected cortex were unchanged after trauma, suggesting that Pten abundance globally had not increased but rather Pten subcellular location in affected neurons had changed. Following experimental injury, the number of neurons with nuclear Pten was reduced in heterozygous mice (Ndfip1(+/-)) although lesion volumes were increased. We conclude that nuclear trafficking of Pten following injury leads to neuron survival not death.

  7. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

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    Kanoto, Masafumi, E-mail: mkanoto@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Hosoya, Takaaki, E-mail: thosoya@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Toyoguchi, Yuuki, E-mail: c-elegans_0201g@mail.goo.ne.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Oda, Atsuko, E-mail: a.oda@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan)

    2013-01-15

    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis.

  8. Carvedilol protects bone marrow stem cells against hydrogen peroxide-induced cell death via PI3K-AKT pathway.

    Science.gov (United States)

    Chen, Meihui; Chen, Shudong; Lin, Dingkun

    2016-03-01

    Carvedilol, a nonselective β-adrenergic receptor blocker, has been reported to exert potent anti-oxidative activities. In the present study, we aimed to investigate the effects of carvedilol against hydrogen peroxide (H2O2)-induced bone marrow-derived mesenchymal stem cells (BMSCs) death, which imitate the microenvironment surrounding transplanted cells in the injured spinal cord in vitro. Carvedilol significantly reduced H2O2-induced reactive oxygen species production, apoptosis and subsequent cell death. LY294002, the PI3K inhibitor, blocked the protective effects and up-regulation of Akt phosphorylation of carvedilol. Together, our results showed that carvedilol protects H2O2-induced BMSCs cell death partly through PI3K-Akt pathway, suggesting carvedilol could be used in combination with BMSCs for the treatment of spinal cord injury by improving the cell survival and oxidative stress microenvironments.

  9. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

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    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  10. Quality of Care of Nursing from Brain Death Patient in ICU Wards

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    Seyedeh Toktam Masoumian Hoseini

    2015-04-01

    Full Text Available Introduction: Nowadays, Intensive Care Unit (ICU nurses play a significant and key role in the care of brain dead patients and their families, therefore their Practice extremely important to the success of organ donation. To assess ICU nurse's practice in relation to nurse's role in the organ donation process from brain dead patients in Iran. Materials and Methods:In a cross-sectional analytical study 90 ICU nurses in Ghaem and Imam Reza Hospitals in Mashhad through stratified random sampling allocation method were selected. Data collection tools included a questionnaire on demographic information, factors influencing nurse's practice during the organ donation process and surveying "nurse's practice in relation to their roles in the organ donation process." Results: 90 nurses participated in this study. (70.0% of the research subjects had spoken with their own families about organ donation, and (20.0% had organ donation cards. Practice scores were calculated on a scale of 100. The mean score of nurses' practice was (6.04± 3.66. 96.7% of nurses’ weak practice in terms of their roles in the organ donation process. Conclusion: As a result, they do not have adequate practice regard nurse's role in organ donation process and in relation to brain death patient and their families. Therefore it is suggested to include nursing courses in the organ donation process and organ transplantation as well as educational programs to acquaint nurses with their roles in the process to improve their practice by different training methods.

  11. Reconstruction of brain circuitry by neural transplants generated from pluripotent stem cells.

    Science.gov (United States)

    Thompson, Lachlan H; Björklund, Anders

    2015-07-01

    Pluripotent stem cells (embryonic stem cells, ESCs, and induced pluripotent stem cells, iPSCs) have the capacity to generate neural progenitors that are intrinsically patterned to undergo differentiation into specific neuronal subtypes and express in vivo properties that match the ones formed during normal embryonic development. Remarkable progress has been made in this field during recent years thanks to the development of more refined protocols for the generation of transplantable neuronal progenitors from pluripotent stem cells, and the access to new tools for tracing of neuronal connectivity and assessment of integration and function of grafted neurons. Recent studies in brains of neonatal mice or rats, as well as in rodent models of brain or spinal cord damage, have shown that ESC- or iPSC-derived neural progenitors can be made to survive and differentiate after transplantation, and that they possess a remarkable capacity to extend axons over long distances and become functionally integrated into host neural circuitry. Here, we summarize these recent developments in the perspective of earlier studies using intracerebral and intraspinal transplants of primary neurons derived from fetal brain, with special focus on the ability of human ESC- and iPSC-derived progenitors to reconstruct damaged neural circuitry in cortex, hippocampus, the nigrostriatal system and the spinal cord, and we discuss the intrinsic and extrinsic factors that determine the growth properties of the grafted neurons and their capacity to establish target-specific long-distance axonal connections in the damaged host brain.

  12. Conductive Hearing Loss during Infancy: Effects on Later Auditory Brain Stem Electrophysiology.

    Science.gov (United States)

    Gunnarson, Adele D.; Finitzo, Terese

    1991-01-01

    Long-term effects on auditory electrophysiology from early fluctuating hearing loss were studied in 27 children, aged 5 to 7 years, who had been evaluated originally in infancy. Findings suggested that early fluctuating hearing loss disrupts later auditory brain stem electrophysiology. (Author/DB)

  13. Paediatric brain-stem gliomas: MRI, FDG-PET and histological grading correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jong Won; Kim, In-One; Cheon, Jung-Eun; Kim, Woo Sun; Moon, Sung Gyu; Kim, Tae Jung; Yeon, Kyung Mo [Seoul National University Hospital, Department of Radiology, Seoul (Korea); Chi, Je Geun [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea); Wang, Kyu-Chang [Seoul National University College of Medicine, Department of Neurosurgery, Seoul (Korea); Chung, June Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea)

    2006-09-15

    MRI and FDG-PET may predict the histological grading of paediatric brain-stem gliomas. To assess MRI findings and metabolic imaging using FDG-PET of brain-stem gliomas based on histological grading. Included in the study were 20 paediatric patients (age 3-14 years, mean 8.2 years) with brain-stem glioma (five glioblastomas, ten anaplastic astrocytomas and five low-grade astrocytomas). MR images were assessed for the anatomical site of tumour origin, focality, pattern of tumour growth, and enhancement. All glioblastomas were located in the pons and showed diffuse pontine enlargement with focally exophytic features. Eight anaplastic astrocytomas were located in the pons and demonstrated diffuse pontine enlargement without exophytic features. Low-grade astrocytomas were located in the pons, midbrain or medulla and showed focally exophytic growth features and peripheral enhancement. In 12 patients in whom FDG-PET was undertaken, glioblastomas showed hypermetabolic or hypometabolic lesions, anaplastic astrocytomas showed no metabolic change or hypometabolic lesions and low-grade astrocytomas showed hypometabolism compared with the cerebellum. MRI findings correlated well with histological grading of brain-stem gliomas and MRI may therefore predict the histological grading. FDG-PET may be helpful in differentiating between anaplastic astrocytoma and glioblastomas among high-grade tumours. (orig.)

  14. Intranasal mesenchymal stem cell treatment for neonatal brain damage : long-term cognitive and sensorimotor improvement

    NARCIS (Netherlands)

    Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; van Bel, Frank; Kas, Martien J H; Kavelaars, Annemieke; Heijnen, Cobi J

    2013-01-01

    Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic wi

  15. Auditory Brain Stem Processing in Reptiles and Amphibians: Roles of Coupled Ears

    DEFF Research Database (Denmark)

    Willis, Katie L.; Christensen-Dalsgaard, Jakob; Carr, Catherine

    2014-01-01

    of anurans (frogs), reptiles (including birds), and mammals should all be more similar within each group than among the groups. Although there is large variation in the peripheral auditory system, there is evidence that auditory brain stem nuclei in tetrapods are homologous and have similar functions among...

  16. Infrequent near death experiences in severe brain injury survivors - A quantitative and qualitative study

    Directory of Open Access Journals (Sweden)

    Yongmei Hou

    2013-01-01

    Full Text Available Background: Near death experiences (NDE are receiving increasing attention by the scientific community because not only do they provide a glimpse of the complexity of the mind-brain interactions in ′near-death′ circumstances but also because they have significant and long lasting effects on various psychological aspects of the survivors. The over-all incidence-reports of NDEs in literature have varied widely from a modest Figure of 10% to around 35%, even up to an incredible Figure of 72% in persons who have faced close brush with death. Somewhat similar to this range of difference in incidences are the differences prevalent in the opinions that theorists and researchers harbor around the world for explaining this phenomena. None the less, objective evidences have supported physiological theories the most. A wide range of physiological processes have been targeted for explaining NDEs. These include cerebral anoxia, chemical alterations like hypercapnia, presence of endorphins, ketamine, and serotonin, or abnormal activity of the temporal lobe or the limbic system. In spite of the fact that the physiological theories of NDEs have revolved around the derangements in brain, no study till date has taken up the task of evaluating the experiences of near-death in patients where specific injury has been to brain. Most of them have evaluated NDEs in cardiac-arrest patients. Post-traumatic coma is one such state regarding which the literature seriously lacks any information related to NDEs. Patients recollecting any memory of their post-traumatic coma are valuable assets for NDE researchers and needs special attention. Materials and Methods: Our present study was aimed at collecting this valuable information from survivors of severe head injury after a prolonged coma. The study was conducted in the head injury department of Guangdong 999 Brain hospital, Guangzhou, China. Patients included in the study were the ones Recovered from the posttraumatic

  17. Analysis on the training effect of criteria and practical guidance for determination of brain death: electroencephalogram

    Directory of Open Access Journals (Sweden)

    Wei-bi CHEN

    2015-12-01

    Full Text Available Objective To analyze the training results of electroencephalogram (EEG for brain death determination and to improve the training program. Methods A total of 114 trainees received theoretical training, simulation skills training, bedside skills training and test analysis. The composition of the trainees and the results of EEG tests were analyzed. The error rates of 5 knowledge points of EEG tests were calculated. Univariate and multivariate backward Logistic regression analyses were used to analyze the influence of factors including sex, age, specialty, professional category, professional qualification and hospital level on the error rates. Results All of 114 trainees came from 72 hospitals. Among them, 91 trainees (79.82% were between 30-49 years old, 108 trainees (94.74% came from third grade, grade A hospitals, and most of them were from Department of Neurology (57.89% , 66/114 and Electrophysiology (19.30% , 22/114. There were 98 clinicians (85.96% and 52 trainees (45.61% had intermediate certificate. Of the 5 knowledge points, the total error rate was 9.19% (204/2221. Among them, the error rate of parameter setting was the highest (11.40% , 26/228, followed by those of result determination (10.44%, 80/766, recording techniques (10.25%, 69/673, environmental requirements (7.46%, 17/228 and pitfalls (3.68%, 12/326. The error rate of trainees who were older than 50 was significantly higher than that in other ages (P = 0.000, for all. The error rate of technicians was higher than that of clinicians (P = 0.039. Univariate and multivariate Logistic regression analyses showed that age was independent risk factor associated with high error rates (OR = 1.382, 95%CI: 1.156-1.652; P = 0.000. Conclusions Among the trainees, degree of mastering the knowledge points is different. The training program should be optimized according to the trainees. More attention should be paid to the difference of EEG between brain death determination and routine check to

  18. Transcranial Doppler ultrasound in the diagnosis of brain death. Is it useful or does it delay the diagnosis?

    Science.gov (United States)

    Escudero, D; Otero, J; Quindós, B; Viña, L

    2015-05-01

    Transcranial Doppler ultrasound is able to demonstrate cerebral circulatory arrest associated to brain death, being especially useful in sedated patients, or in those in which complete neurological exploration is not possible. Transcranial Doppler ulstrasound is a portable, noninvasive and high-availability technique. Among its limitations, mention must be made of the absence of acoustic windows and false-negative cases. In patients clinically diagnosed with brain death, with open skulls or with anoxia as the cause of death, cerebral blood flow can be observed by ultrasound, since cerebral circulatory arrest is not always synchronized to the clinical diagnosis. The diagnostic rate is therefore time-dependent, and this fact that must be recognized in order to avoid delays in death certification. Despite its limitations, transcranial Doppler ulstrasound helps solve common diagnostic problems, avoids the unnecessary consumption of resources, and can optimize organ harvesting for transplantation.

  19. Tropism mechanism of stem cells targeting injured brain tissues by stromal cell-derived factor-1

    Institute of Scientific and Technical Information of China (English)

    ZHANG Sai; LIU Xiao-zhi; LIU Zhen-lin; SHANG Chong-zhi; HU Qun-liang

    2009-01-01

    Objective: To explore the role and function of stromal cell-derived factor- 1 (SDF- 1) in stem cells migrating into injured brain area.Methods: Rat-derived nerve stem cells (NSCs) were isolated and cultured routinely. Transwell system was used to observe the migration ability of NSCs into injured nerve cells. Immunocytochemistry was used to explore the expression of chemotactic factor receptor-4 (CXCR-4) in NSCs. In vivo, we applied immunofluorescence technique to observe the migration of NSCs into injured brain area. Immunofluorescence technique and Western blotting were used to test expression level of SDF- 1. After AMD3100 (a special chemical blocker) blocking CXCR-4, the migration ability of NSCs was tested in vivo and in vitro, respectively.Results: NSCs displayed specific tropism for injured nerve cells or traumatic brain area in vivo and in vitro. The expression level of SDF-1 in traumatic brain area increased remarkably and the expression level of CXCR-4 in the NSCs increased simultaneously. After AMD3100 blocking the expression of CXCR-4, the migration ability of NSCs decreased significantly both in vivo and in vitro.Conclusions: SDF-1 may play a key role in stem cells migrating into injured brain area through specially combining with CXCR-4.

  20. MRI measurements of the brain stem and cerebellum in high functioning autistic children

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Toshiaki; Tayama, Masanobu; Miyazaki, Masahito; Murakawa, Kazuyoshi; Kuroda, Yasuhiro (Tokushima Univ. (Japan). School of Medicine)

    1994-01-01

    To determine involvements of the brain stem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. The development of the cerebellar vermis area was delayed in autistic children as compared with that in the control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children. (author).

  1. [Deceased organ donors, legal regulations governing diagnosis of brain death, overview of donors and liver transplants in the Czech Republic].

    Science.gov (United States)

    Pokorná, E

    2013-08-01

    The key restriction of transplantation medicine globally, as well as in the Czech Republic, concerns the lack of organs. The number of deceased donors, and thus the availability of organ transplants, has been stagnating in our country. The paper describes current legal regulations governing the dia-gnosis of brain death and primary legal and medical criteria for the contraindication of the deceased for organ explantation, gives an overview of the number of liver transplants, age structure, and diagnosis resulting in brain death of the deceased liver donors in the Czech Republic.

  2. Complement mediated renal inflammation induced by donor brain death : role of renal C5a-C5aR interaction

    NARCIS (Netherlands)

    van Werkhoven, M. B.; Damman, J.; van Dijk, M. C. R. F.; Daha, M. R.; de Jong, I. J.; Leliveld, A.; Krikke, C.; Leuvenink, H. G.; van Goor, H.; van Son, W. J.; Olinga, P.; Hillebrands, J. -L.; Seelen, M. A. J.

    2013-01-01

    Kidneys retrieved from brain-dead donors have impaired allograft function after transplantation compared to kidneys from living donors. Donor brain death (BD) triggers inflammatory responses, including both systemic and local complement activation. The mechanism by which systemic activated complemen

  3. Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ozelame, Rodrigo V.; Shroff, Manohar; Wood, Bradley; Bouffet, Eric; Bartels, Ute; Drake, James M.; Hawkins, Cynthia; Blaser, Susan [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, Ontario (Canada)

    2006-04-15

    Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. (orig.)

  4. [A case of a child who developed Cushing reflex after a clinical diagnosis of brain death].

    Science.gov (United States)

    Enoki, Hideo

    2007-01-01

    The author presents a case of brain death caused by salmonella encephalopathy in a 1-year-old girl. The patient suffered from fever, convulsive status, and coma. On the 5th day, her respiration was arrested. At that time, we confirmed the absence of brainstem reflexes. An electroencephalogram (EEG) showed a flat pattern. Only wave I was recordable in auditory brainstem responses (ABR). On the 6th day, we obtained a flat EEG and a disappearance of all components of ABR. A simultaneous elevation of her heart rate and blood pressure was observed 14 to 18 hours after the respiratory arrest. This phenomenon was equivalent to the Cushing reflex, which represents an autoregulation against increased intracranial pressure. Our case suggested that the activity of a part of the brainstem was preserved in spite of the absence of activities in EEG, ABR and brainstem reflexes at 14 hours after the onset of apnea.

  5. Potential brain death organ donors - challenges and prospects: A single center retrospective review

    Directory of Open Access Journals (Sweden)

    Yousef Al-Maslamani

    2014-01-01

    Full Text Available Organ donation after brain death (BD is a major source for obtaining transplantable organs for patients with end-stage organ disease (ESOD. This retrospective, descriptive study was carried out on all potential BD patients admitted in different intensive care units (ICUs of the Hamad medical Corporation (HMC, Doha, Qatar during a period from January 2011 to April 2012. Our aim was to evaluate various demographic criteria and challenges of organ donation among potential BD organ donors and plan a strategy to improve the rate of organ donation in Qatar. Various aspects of BD patients in the ICUs and their possible effects on organ donation were studied. The time intervals analyzed to determine the possible causes of delay of organ retrieval were: time of diagnosing fixed dilated pupils in the ICU, to performing the first BD test, then to the second BD test, to family approach, to organ retrieval and/or circulatory death (CD without organ retrieval. There were a total of 116 potential BD organ donors of whom 96 (82.75% were males and 20 (17.25% were females. Brain hemorrhage and head injury contributed to 37 (31.9% and 32 (27.6% BD cases, respectively. Time interval between diagnosing fixed dilated pupil and performing the first test of BD was delayed >24 h in 79% of the cases and between the first and second BD tests was >6 h in 70.8% of the cases. This delay is not compatible with the Hamad Medical Corporation (HMC policy for BD diagnosis and resulted in a low number of organs retrieved. BD organ donation, a potential source for organs to save patients with ESOD has several pitfalls and every effort should be made to increase the awareness of the public as well as medical personnel to optimize donation efficacy.

  6. Does State Merit-Based Aid Stem Brain Drain?

    Science.gov (United States)

    Zhang, Liang; Ness, Erik C.

    2010-01-01

    In this study, the authors use college enrollment and migration data to test the brain drain hypothesis. Their results suggest that state merit scholarship programs do indeed stanch the migration of "best and brightest" students to other states. In the aggregate and on average, the implementation of state merit aid programs increases the…

  7. Stem Cells Expand Insights into Human Brain Evolution.

    Science.gov (United States)

    Dyer, Michael A

    2016-04-07

    Substantial expansion in the number of cerebral cortex neurons is thought to underlie cognitive differences between humans and other primates, although the mechanisms underlying this expansion are unclear. Otani et al. (2016) utilize PSC-derived brain organoids to study how species-specific differences in cortical progenitor proliferation may underlie cortical evolution.

  8. Aberrant brain-stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Lee JH

    2016-08-01

    Full Text Available Ji Han Lee,1 Won Sang Jung,2 Woo Hee Choi,3 Hyun Kook Lim4 1Washington University in St Louis, St Louis, MO, USA; 2Department of Radiology, 3Department of Nuclear Medicine, 4Department of Psychiatry, Saint Vincent Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea Objective: Among patients with Alzheimer’s disease (AD, sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD.Materials and methods: In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology.Results: Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group.Conclusion: This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings. Keywords: Alzheimer’s disease, sleep, brain stem, MRI, shape analysis

  9. Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury.

    Science.gov (United States)

    Jin, Yichao; Lin, Yingying; Feng, Jun-feng; Jia, Feng; Gao, Guo-yi; Jiang, Ji-yao

    2015-07-15

    Here, we evaluated changes in autophagy after post-traumatic brain injury (TBI) followed by moderate hypothermia in rats. Adult male Sprague-Dawley rats were randomly divided into four groups: sham injury with normothermia group (37 °C); sham injury with hypothermia group (32 °C); TBI with normothermia group (TNG; 37 °C); and TBI with hypothermia group (THG; 32 °C). Injury was induced by a fluid percussion TBI device. Moderate hypothermia (32 °C) was achieved by partial immersion in a water bath (0 °C) under general anesthesia for 4 h. All rats were killed at 24 h after fluid percussion TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; terminal deoxynucleoitidyl transferase-mediated nick end labeling staining was used to determine cell death in ipsilateral hippocampus. Immunohistochemistry and western blotting of microtubule-associated protein light chain 3 (LC3), Beclin-1, as well as transmission electron microscopy performed to assess changes in autophagy. At 24 h after TBI, the cell death index was 27.90 ± 2.36% in TNG and 14.90 ± 1.52% in THG. Expression level of LC3 and Beclin-1 were significantly increased after TBI and were further up-regulated after post-TBI hypothermia. Further, ultrastructural observations showed that there was a marked increase of autophagosomes and autolysosomes in ipsilateral hippocampus after post-TBI hypothermia. Our data demonstrated that moderate hypothermia significantly attenuated cell death and increased autophagy in ipsilateral hippocampus after fluid percussion TBI. In conclusion, autophagy pathway may participate in the neuroprotective effect of post-TBI hypothermia.

  10. Classic and novel stem cell niches in brain homeostasis and repair.

    Science.gov (United States)

    Lin, Ruihe; Iacovitti, Lorraine

    2015-12-02

    Neural stem cells (NSCs) critical for the continued production of new neurons and glia are sequestered in distinct areas of the brain called stem cell niches. Until recently, only two forebrain sites, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus, have been recognized adult stem cell niches (Alvarez-Buylla and Lim, 2004; Doetsch et al., 1999a, 1999b; Doetsch, 2003a, 2003b; Lie et al., 2004; Ming and Song, 2005). Nonetheless, the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury (Barnabé-Heider et al., 2010; Carlén et al., 2009; Decimo et al., 2012; Lin et al., 2015; Lindvall and Kokaia, 2008; Robins et al., 2013) or other inductive stimuli (Bennett et al., 2009; Cunningham et al., 2012; Decimo et al., 2011; Kokoeva et al., 2007, 2005; Lee et al., 2012a, 2012b; Migaud et al., 2010; Pencea et al., 2001b; Sanin et al., 2013; Suh et al., 2007; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). This review focuses on the role of these novel and classic brain niches in maintaining adult neurogenesis and gliogenesis in response to normal physiological and injury-related pathological cues. This article is part of a Special Issue entitled SI: Neuroprotection.

  11. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    Science.gov (United States)

    Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

  12. Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Dhruv Sareen

    Full Text Available Spinal muscular atrophy (SMA is a genetic disorder caused by a deletion of the survival motor neuron 1 gene leading to motor neuron loss, muscle atrophy, paralysis, and death. We show here that induced pluripotent stem cell (iPSC lines generated from two Type I SMA subjects-one produced with lentiviral constructs and the second using a virus-free plasmid-based approach-recapitulate the disease phenotype and generate significantly fewer motor neurons at later developmental time periods in culture compared to two separate control subject iPSC lines. During motor neuron development, both SMA lines showed an increase in Fas ligand-mediated apoptosis and increased caspase-8 and-3 activation. Importantly, this could be mitigated by addition of either a Fas blocking antibody or a caspase-3 inhibitor. Together, these data further validate this human stem cell model of SMA, suggesting that specific inhibitors of apoptotic pathways may be beneficial for patients.

  13. Neurogenesis in the brain stem of the rabbit: an autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Oblinger, M.M.; Das, G.D.

    1981-03-20

    With the aid of (/sup 3/H)-thymidine autoradiography, neurogenesis was documented in the nuclear groups of the medulla oblongata, pons, and mid-brain, as well as in the brain stem reticular formation of the rabbit. Following single injections of (/sup 3/H)-thymidine, counts were taken of intensely labeled neurons within the nuclei of the functional columns related to the cranial nerves, nuclei of several other functional classifications, and nuclei that did not fit into a functional category. In the brain stem as a whole, neurogenesis was found to occur between days 10.0 and 18.5 of gestation: however, the majority of nuclei studied contained intensely neurons only between days 12.0 and 15.0. Only in the pontine nucleus and the tectum were intensely labeled cells observed as late as day 18.5. Directional gradients of histogenesis were often observed within, as well as between, various nuclei. Within the nuclear columns related to the cranial nerves, a clear mediolateral spread of neurogenesis was observable such that nuclei of the motor columns reached a peak in neurogenesis before those in the sensory columns. Likewise, a mediolateral proliferation pattern was seen in the brain stem reticular formation. Other individual directional gradients were discernible; however, in the brain stem as a whole, distinct overall gradients were not observable. In many individual nuclei, gradients in neuron size were observed such that large neurons preferentially arose prior to smaller neurons. Information pertaining to gradients in neurogenesis, as well as to relationships among functionally related nuclei, are discussed.

  14. Prophylactic Antiarrhythmic Effect of Anesthetics at Subanesthetic Concentration on Epinephrine-Induced Arrhythmias in Rats after Brain Death

    Directory of Open Access Journals (Sweden)

    Yuka Miyata

    2015-01-01

    Full Text Available The present study using brain death model of rats was designed to examine whether prophylactic administration of volatile anesthetics and propofol prevent the epinephrine-induced arrhythmias. A Fogarty catheter was placed intracranially for induction of brain death. After brain death, the rats were randomly assigned to five groups: the control group (no anesthetics, the sevoflurane group (0.8%, the isoflurane group (0.5%, the halothane group (0.3%, and the propofol group (195 μg·kg−1·min−1. These anesthetics were about 30% of ED50 of each anesthetic. The arrhythmogenic dose of epinephrine was determined in each anesthetic group. In addition, we examined left ventricular levels of connexin 43 phosphorylation 30 min after administration of each anesthetic with Western blot analysis. The arrhythmogenic dose of epinephrine in the sevoflurane group was significantly higher than that in the control group, while the arrhythmogenic dose of epinephrine in any other anesthetic group was not different. On the other hand, the ratio of phosphorylated-connexin 43/total connexin 43 was also similar among the study groups. Thus, prophylactic administration of subanesthetic dose of sevoflurane is effective in preventing epinephrine-induced arrhythmias after brain death, but phosphorylation of connexin is not involved in the antiarrhythmic property of sevoflurane.

  15. Prophylactic antiarrhythmic effect of anesthetics at subanesthetic concentration on epinephrine-induced arrhythmias in rats after brain death.

    Science.gov (United States)

    Miyata, Yuka; Iwasaki, Mitsuo; Yamanaka, Hiroo; Sato, Masanori; Kamibayashi, Takahiko; Fujino, Yuji; Hayashi, Yukio

    2015-01-01

    The present study using brain death model of rats was designed to examine whether prophylactic administration of volatile anesthetics and propofol prevent the epinephrine-induced arrhythmias. A Fogarty catheter was placed intracranially for induction of brain death. After brain death, the rats were randomly assigned to five groups: the control group (no anesthetics), the sevoflurane group (0.8%), the isoflurane group (0.5%), the halothane group (0.3%), and the propofol group (195 μg·kg(-1) ·min(-1)). These anesthetics were about 30% of ED50 of each anesthetic. The arrhythmogenic dose of epinephrine was determined in each anesthetic group. In addition, we examined left ventricular levels of connexin 43 phosphorylation 30 min after administration of each anesthetic with Western blot analysis. The arrhythmogenic dose of epinephrine in the sevoflurane group was significantly higher than that in the control group, while the arrhythmogenic dose of epinephrine in any other anesthetic group was not different. On the other hand, the ratio of phosphorylated-connexin 43/total connexin 43 was also similar among the study groups. Thus, prophylactic administration of subanesthetic dose of sevoflurane is effective in preventing epinephrine-induced arrhythmias after brain death, but phosphorylation of connexin is not involved in the antiarrhythmic property of sevoflurane.

  16. Neural stem cell transplantation with Nogo-66 receptor gene silencing to treat severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Jianjun Zhang; Jingjian Ma; Yuan Mu; Yinghui Zhuang

    2011-01-01

    Inhibition of neurite growth, which is mediated by the Nogo-66 receptor (NgR), affects nerve regeneration following neural stem cell (NSC) transplantation. The present study utilized RNA interference to silence NgR gene expression in NSCs, which were subsequently transplanted into rats with traumatic brain injury. Following transplantation of NSCs transfected with small interfering RNA,typical neural cell-like morphology was detected in injured brain tissues, and was accompanied by absence of brain tissue cavity, increased growth-associated protein 43 mRNA and protein expression,and improved neurological function compared with NSC transplantation alone. Results demonstrated that NSC transplantation with silenced NgR gene promoted functional recovery following brain injury.

  17. Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells.

    Science.gov (United States)

    Lippmann, Ethan S; Azarin, Samira M; Kay, Jennifer E; Nessler, Randy A; Wilson, Hannah K; Al-Ahmad, Abraham; Palecek, Sean P; Shusta, Eric V

    2012-08-01

    The blood-brain barrier (BBB) is crucial to the health of the brain and is often compromised in neurological disease. Moreover, because of its barrier properties, this endothelial interface restricts uptake of neurotherapeutics. Thus, a renewable source of human BBB endothelium could spur brain research and pharmaceutical development. Here we show that endothelial cells derived from human pluripotent stem cells (hPSCs) acquire BBB properties when co-differentiated with neural cells that provide relevant cues, including those involved in Wnt/β-catenin signaling. The resulting endothelial cells have many BBB attributes, including well-organized tight junctions, appropriate expression of nutrient transporters and polarized efflux transporter activity. Notably, they respond to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance (1,450 ± 140 Ω cm2), and they possess molecular permeability that correlates well with in vivo rodent blood-brain transfer coefficients.

  18. TGFβ lengthens the G1 phase of stem cells in aged mouse brain.

    Science.gov (United States)

    Daynac, Mathieu; Pineda, Jose R; Chicheportiche, Alexandra; Gauthier, Laurent R; Morizur, Lise; Boussin, François D; Mouthon, Marc-André

    2014-12-01

    Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells.

  19. Brain-dead patients are not cadavers: the need to revise the definition of death in Muslim communities.

    Science.gov (United States)

    Rady, Mohamed Y; Verheijde, Joseph L

    2013-03-01

    The utilitarian construct of two alternative criteria of human death increases the supply of transplantable organs at the end of life. Neither the neurological criterion (heart-beating donation) nor the circulatory criterion (non-heart-beating donation) is grounded in scientific evidence but based on philosophical reasoning. A utilitarian death definition can have unintended consequences for dying Muslim patients: (1) the expedited process of determining death for retrieval of transplantable organs can lead to diagnostic errors, (2) the equivalence of brain death with human death may be incorrect, and (3) end-of-life religious values and traditional rituals may be sacrificed. Therefore, it is imperative to reevaluate the two different types and criteria of death introduced by the Resolution (Fatwa) of the Council of Islamic Jurisprudence on Resuscitation Apparatus in 1986. Although we recognize that this Fatwa was based on best scientific evidence available at that time, more recent evidence shows that it rests on outdated knowledge and understanding of the phenomenon of human death. We recommend redefining death in Islam to reaffirm the singularity of this biological phenomenon as revealed in the Quran 14 centuries ago.

  20. Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke.

    Science.gov (United States)

    Chang, Alice Y W; Li, Faith C H; Huang, Chi-Wei; Wu, Julie C C; Dai, Kuang-Yu; Chen, Chang-Han; Li, Shau-Hsuan; Su, Chia-Hao; Wu, Re-Wen

    2014-11-01

    Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke-elicited pressor response. Experiments were performed in male adult Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response.

  1. Murine cytomegalovirus infection of neural stem cells alters neurogenesis in the developing brain.

    Directory of Open Access Journals (Sweden)

    Manohar B Mutnal

    Full Text Available BACKGROUND: Congenital cytomegalovirus (CMV brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV and the pattern of injury to the developing brain. METHODOLOGY/PRINCIPAL FINDINGS: We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection. CONCLUSIONS: MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons.

  2. From pluripotent stem cells to multifunctional cordocytic phenotypes in the human brain: an ultrastructural study.

    Science.gov (United States)

    Pais, Viorel; Danaila, Leon; Pais, Emil

    2012-08-01

    Light microscopy and transmission electron microscopy were used to investigate surgical cases in a variety of pathological conditions (thromboses, tumors, cerebrovascular malformations, Moyamoya disease) to identify and characterize different phenotypes belonging to a new interstitial cell recently described ultrastructurally in the brain and here named "cordocyte." Also, this work is an attempt to identify and characterize precursor/stem cells for cordocytic lineage in the perivascular areas, within perivascular nerves and pia mater (now considered a cordocytic-vascular tissue). Unexpected relationships and functions emerge from observations concerning these phenotypes, almost ubiquitous, but not yet fully studied in the brain.

  3. Delayed radiation-induced necrosis of the brain stem; A case report

    Energy Technology Data Exchange (ETDEWEB)

    Yukawa, Osamu; Kodama, Yasunori; Kyoda, Jun; Yuki, Kiyoshi; Taniguchi, Eiji; Katayama, Shoichi; Hiroi, Tadashi (National Kure Hospital, Hiroshima (Japan)); Uozumi, Toru

    1993-03-01

    A 46-year-old man had surgery for a mixed glioma of the frontotemporal lobe. Postoperatively he received 50 Gy of irradiation. Sixteen months later he developed left hemiparesis and left facial palsy. MRI revealed lesion brain stem and basal ganglia. Despite chemotherapy and an additional 50 Gy dose, the patient deteriorated. Autopsy revealed a wide spread radiation-induced necrosis in the right cerebral hemisphere, midbrain and pons. In radiation therapy, great care must be taken to protect the normal brain tissue. (author).

  4. Effect of Acupuncture on the Auditory Evoked Brain Stem Potential in Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    王玲玲; 何崇; 刘跃光; 朱莉莉

    2002-01-01

    @@ Under the auditory evoked brain stem potential (ABP) examination, the latent period of V wave and the intermittent periods of III-V peak and I-V peak were significantly shortened in Parkinson's disease patients of the treatment group (N=29) after acupuncture treatment. The difference of cumulative scores in Webster's scale was also decreased in correlation analysis. The increase of dopamine in the brain and the excitability of the dopamine neurons may contribute to the therapeutic effects, in TCM terms, of subduing the pathogenic wind and tranquilizing the mind.

  5. Effect of acupuncture on the auditory evoked brain stem potential in Parkinson's disease.

    Science.gov (United States)

    Wang, Lingling; He, Chong; Liu, Yueguang; Zhu, Lili

    2002-03-01

    Under the auditory evoked brain stem potential (ABP) examination, the latent period of V wave and the intermittent periods of III-V peak and I-V peak were significantly shortened in Parkinson's disease patients of the treatment group (N = 29) after acupuncture treatment. The difference of cumulative scores in Webster's scale was also decreased in correlation analysis. The increase of dopamine in the brain and the excitability of the dopamine neurons may contribute to the therapeutic effects, in TCM terms, of subduing the pathogenic wind and tranquilizing the mind.

  6. Long-term meditation is associated with increased gray matter density in the brain stem

    DEFF Research Database (Denmark)

    Vestergaard-Poulsen, Peter; Beek, Martijn van; Skewes, Joshua

    2009-01-01

    Extensive practice involving sustained attention can lead to changes in brain structure. Here, we report evidence of structural differences in the lower brainstem of participants engaged in the long-term practice of meditation. Using magnetic resonance imaging, we observed higher gray matter...... density in lower brain stem regions of experienced meditators compared with age-matched nonmeditators. Our findings show that long-term practitioners of meditation have structural differences in brainstem regions concerned with cardiorespiratory control. This could account for some...... of the cardiorespiratory parasympathetic effects and traits, as well as the cognitive, emotional, and immunoreactive impact reported in several studies of different meditation practices....

  7. Integrated But Not Whole? Applying an Ontological Account of Human Organismal Unity to the Brain Death Debate.

    Science.gov (United States)

    Moschella, Melissa

    2016-10-01

    As is clear in the 2008 report of the President's Council on Bioethics, the brain death debate is plagued by ambiguity in the use of such key terms as 'integration' and 'wholeness'. Addressing this problem, I offer a plausible ontological account of organismal unity drawing on the work of Hoffman and Rosenkrantz, and then apply that account to the case of brain death, concluding that a brain dead body lacks the unity proper to a human organism, and has therefore undergone a substantial change. I also show how my view can explain hard cases better than one in which biological integration (as understood by Alan Shewmon and the President's Council) is taken to imply ontological wholeness or unity.

  8. Endovascular treatment of brain-stem arteriovenous malformations: safety and efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, H.M.; Wang, Y.H.; Chen, Y.F.; Huang, K.M. [Department of Medical Imaging, National Taiwan University Hospital, 7 Chung-Shan South Road, 10016, Taipei (Taiwan); Tu, Y.K. [Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Road, 1001, Taipei (Taiwan)

    2003-09-01

    Our purpose was to evaluate the safety and efficacy of endovascular treatment of brain-stem arteriovenous malformations (AVMs), reviewing six cases managed in the last 5 years. There were four patients who presented with bleeding, one with a progressive neurological deficit and one with obstructive hydrocephalus. Of the six patients, one showed 100%, one 90%, two 75% and two about 50% angiographic obliteration of the AVM after embolisation; the volume decreased about 75% on average. Five patients had a good outcome and one an acceptable outcome, with a mild postprocedure neurological deficit; none had further bleeding during midterm follow-up. Endovascular management of a brain-stem AVM may be an alternative to treatment such as radiosurgery and microsurgery in selected cases. It may be not as risky as previously thought. Embolisation can reduce the size of the AVM and possibly make it more treatable by radiosurgery and decrease the possibility of radiation injury. (orig.)

  9. Microinjection of membrane-impermeable molecules into single neural stem cells in brain tissue.

    Science.gov (United States)

    Wong, Fong Kuan; Haffner, Christiane; Huttner, Wieland B; Taverna, Elena

    2014-05-01

    This microinjection protocol allows the manipulation and tracking of neural stem and progenitor cells in tissue at single-cell resolution. We demonstrate how to apply microinjection to organotypic brain slices obtained from mice and ferrets; however, our technique is not limited to mouse and ferret embryos, but provides a means of introducing a wide variety of membrane-impermeable molecules (e.g., nucleic acids, proteins, hydrophilic compounds) into neural stem and progenitor cells of any developing mammalian brain. Microinjection experiments are conducted by using a phase-contrast microscope equipped with epifluorescence, a transjector and a micromanipulator. The procedure normally takes ∼2 h for an experienced researcher, and the entire protocol, including tissue processing, can be performed within 1 week. Thus, microinjection is a unique and versatile method for changing and tracking the fate of a cell in organotypic slice culture.

  10. Robotics, Stem Cells and Brain Computer Interfaces in Rehabilitation and Recovery from Stroke; Updates and Advances

    Science.gov (United States)

    Boninger, Michael L; Wechsler, Lawrence R.; Stein, Joel

    2014-01-01

    Objective To describe the current state and latest advances in robotics, stem cells, and brain computer interfaces in rehabilitation and recovery for stroke. Design The authors of this summary recently reviewed this work as part of a national presentation. The paper represents the information included in each area. Results Each area has seen great advances and challenges as products move to market and experiments are ongoing. Conclusion Robotics, stem cells, and brain computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial PMID:25313662

  11. Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma - a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Lau, S.K.; Wei, W.I.; Sham, J.S.T.; Choy, D.T.K.; Hui, Y. (Queen Mary Hospital, Hong Kong (Hong Kong))

    1992-10-01

    A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway. (Author).

  12. Characteristics of brain stem auditory evoked potentials in children with hearing impairment due to infectious diseases.

    Science.gov (United States)

    Ječmenica, Jovana Radovan; Opančina, Aleksandra Aleksandar Bajec

    2015-05-01

    Among objective audiologic tests, the most important were tests of brain stem auditory evoked potentials. The objective of the study was to test the configuration, degree of hearing loss, and response characteristics of auditory brain stem evoked potentials in children with hearing loss occurred due to infectious disease. A case control study design was used. The study group consisted of 54 patients referred for a hearing test because of infectious diseases caused by other agents or that occurred as congenital infection. Infectious agents have led to the emergence of various forms of sensorineural hearing loss. We have found deviations from the normal values of absolute and interwave latencies in some children in our group. We found that in the group of children who had the diseases such as purulent meningitis, or were born with rubella virus and cytomegalovirus infection, a retrocochlear damage was present in children with and without cochlear damage.

  13. Evaluation of normal and pathologic appearance in skull base and brain stem with metrizamide CT cisternography

    Energy Technology Data Exchange (ETDEWEB)

    Morimura, Tatsuo; Nakano, Masaru; Maeda, Yukio; Yokota, Masayuki; Kokubu, Kiyokazu; Shimada, Tatsuji (Hyogo College of Medicine (Japan))

    1985-02-01

    Metrizamide CT cisternography was performed in accordance with prone 60/sup 0/ head-down method, to study the normal anatomy of the skull base and brain stem. Cases of empty sellae, Rathke's cleft cyst, mucocele trigeminal neurinoma, pons glioma, acoustic neurinoma and jugular foramen tumor were studied together. As side effects of MCTC there were headache, vomiting and appearance of slow waves on EEG, but no convulsion. Transient encephalopathy was noted when 250 mgI/ml, 12 ml, was used. Using MCTC, it is possible to identify the vertebral artery, posterior inferior cerebellar artery, basillar artery, vessels forming Willis ring as well as II, III, V, VII and VIII cranial nerves. Further, by measuring the brain stem parts on various levels, it may become possible to detect early changes of degenerative disease.

  14. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation.

    NARCIS (Netherlands)

    Scheper, G.C.; Klok, T. van der; Andel, R.J. van; Berkel, C.G. van; Sissler, M.; Smet, J.; Muravina, T.I.; Serkov, S.V.; Uziel, G.; Bugiani, M.; Schiffmann, R.; Krageloh-Mann, I.; Smeitink, J.A.M.; Florentz, C.; Coster, R. van; Pronk, J.C.; Knaap, M.S. van der

    2007-01-01

    Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) has recently been defined based on a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. LBSL is an autosomal recessive disease, most often manifesti

  15. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

    Science.gov (United States)

    Alvarim, Larissa T; Nucci, Leopoldo P; Mamani, Javier B; Marti, Luciana C; Aguiar, Marina F; Silva, Helio R; Silva, Gisele S; Nucci-da-Silva, Mariana P; DelBel, Elaine A; Gamarra, Lionel F

    2014-01-01

    The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson’s disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain. PMID:25143726

  16. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review.

    Science.gov (United States)

    Alvarim, Larissa T; Nucci, Leopoldo P; Mamani, Javier B; Marti, Luciana C; Aguiar, Marina F; Silva, Helio R; Silva, Gisele S; Nucci-da-Silva, Mariana P; DelBel, Elaine A; Gamarra, Lionel F

    2014-01-01

    The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.

  17. Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

    We have studied the action of deltamethrin on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the hypoglossal motoneurons, increased the background synaptic noise and reduced the frequency and amplitude of current elicited action...

  18. Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

    Directory of Open Access Journals (Sweden)

    Lars eRoll

    2014-08-01

    Full Text Available The limited regeneration capacity of the adult central nervous system requires strategies to improve recovery of patients. In this context, the interaction of endogenous as well as transplanted stem cells with their environment is crucial. An understanding of the molecular mechanisms could help to improve regeneration by targeted manipulation.In the course of reactive gliosis, astrocytes upregulate Glial fibrillary acidic protein (GFAP and start, in many cases, to proliferate. Beside GFAP, subpopulations of these astroglial cells coexpress neural progenitor markers like Nestin. Although cells express these markers, the proportion of cells that eventually give rise to neurons is limited in many cases in vivo compared to the situation in vitro. In the first section, we present the characteristics of endogenous progenitor-like cells and discuss the differences in their neurogenic potential in vitro and in vivo.As the environment plays an important role for survival, proliferation, migration, and other processes, the second section of the review describes changes in the extracellular matrix (ECM, a complex network that contains numerous signaling molecules. It appears that signals in the damaged central nervous system lead to an activation and de-differentiation of astrocytes, but do not effectively promote neuronal differentiation of these cells. Factors that influence stem cells during development are upregulated in the damaged brain as part of an environment resembling a stem cell niche. We give a general description of the ECM composition, with focus on stem cell-associated factors like the glycoprotein Tenascin-C.Stem cell transplantation is considered as potential treatment strategy. Interaction of transplanted stem cells with the host environment is critical for the outcome of stem cell-based therapies. Possible mechanisms involving the ECM by which transplanted stem cells might improve recovery are discussed in the last section.

  19. The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors.

    Directory of Open Access Journals (Sweden)

    Jin Xu

    Full Text Available The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD. The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD, we aimed to understand how ischemia/reperfusion (I/R injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration.Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13 and DBD (n = 10 livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22 and DBD (n = 13 livers.When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05 and C22 ceramide (p<0.05 were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST of DCD allografts had significantly increased.These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation.

  20. Neurons Differentiated from Transplanted Stem Cells Respond Functionally to Acoustic Stimuli in the Awake Monkey Brain.

    Science.gov (United States)

    Wei, Jing-Kuan; Wang, Wen-Chao; Zhai, Rong-Wei; Zhang, Yu-Hua; Yang, Shang-Chuan; Rizak, Joshua; Li, Ling; Xu, Li-Qi; Liu, Li; Pan, Ming-Ke; Hu, Ying-Zhou; Ghanemi, Abdelaziz; Wu, Jing; Yang, Li-Chuan; Li, Hao; Lv, Long-Bao; Li, Jia-Li; Yao, Yong-Gang; Xu, Lin; Feng, Xiao-Li; Yin, Yong; Qin, Dong-Dong; Hu, Xin-Tian; Wang, Zheng-Bo

    2016-07-26

    Here, we examine whether neurons differentiated from transplanted stem cells can integrate into the host neural network and function in awake animals, a goal of transplanted stem cell therapy in the brain. We have developed a technique in which a small "hole" is created in the inferior colliculus (IC) of rhesus monkeys, then stem cells are transplanted in situ to allow for investigation of their integration into the auditory neural network. We found that some transplanted cells differentiated into mature neurons and formed synaptic input/output connections with the host neurons. In addition, c-Fos expression increased significantly in the cells after acoustic stimulation, and multichannel recordings indicated IC specific tuning activities in response to auditory stimulation. These results suggest that the transplanted cells have the potential to functionally integrate into the host neural network.

  1. Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

    Directory of Open Access Journals (Sweden)

    Hadar Arien-Zakay

    2010-09-01

    Full Text Available The use of stem cells for reparative medicine was first proposed more than three decades ago. Hematopoietic stem cells from bone marrow, peripheral blood and human umbilical cord blood (CB have gained major use for treatment of hematological indications. CB, however, is also a source of cells capable of differentiating into various non-hematopoietic cell types, including neural cells. Several animal model reports have shown that CB cells may be used for treatment of neurological injuries. This review summarizes the information available on the origin of CB-derived neuronal cells and the mechanisms proposed to explain their action. The potential use of stem/progenitor cells for treatment of ischemic brain injuries is discussed. Issues that remain to be resolved at the present stage of preclinical trials are addressed.

  2. Combined Striatum, Brain Stem, and Optic Nerve Involvement due to Mycoplasma pneumoniae in an Ambulatory Child

    Directory of Open Access Journals (Sweden)

    Jin-Won Bae

    2011-05-01

    Full Text Available In children, Mycoplasma pneumoniae encephalitis has been characterized by acute onset of an encephalopathy associated with extrapyramidal symptoms and symmetric basal ganglia with or without brain stem involvement on magnetic resonance imaging. Our case, showing unilateral optic neuritis, ophthalmoplegia, no extrapyramidal symptoms, and typical striatal involvement on magnetic resonance imaging, broadens the spectrum of varying clinical manifestations of childhood M. pneumoniae-associated encephalopathy.

  3. The Regenerative Response of Endogenous Neural Stem/Progenitor Cells to Traumatic Brain Injury

    Science.gov (United States)

    2014-06-09

    neural stem cells in the adjacent SVZ, the largest germinal zone in the mammalian CNS. Ex vivo and in vivo DTI were combined with post-imaging...faults accrued over 50 steps was counted for each hind limb. Controlled Cortical Impact (CCI), which involves craniotomy and impact onto the dura...the subventricular zone (SVZ), a major germinal zone in the adult brain, have potential repair capacity that is not well understood relative to the

  4. [Trismus, trigeminal motor dyssynergy with brain stem lesions (author's transl)].

    Science.gov (United States)

    Jelasic, F; Freitag, V

    1975-08-01

    Paradox activity of masticatory muscles was observed clinically and electromyographically in 4 patients with brain steem lesions who had trismus. There was no activity in the elevators of the jaw on the side affected during voluntary biting, as if the muscles were paralyzed. There was strong activity of the elevators on the side of the trismus on opening the mouth, inactivity on the unaffected side, or inverse activity appeared on both sides. In view of the trigeminal anesthesia on the side of paradox activation, and the absence of pyramidal signs, a stretch reflex mechanism and abolition of inhibition can not be the only basis for these phenomena; so, a disturbance of bilateral synergism, in the sense of an internuclear lesion, is postulated. In one case of motor and sensory paralysis after the extirpation of a meningioma of the cerebellopontine angle, intensive paradox activity was observed, without trismus.

  5. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jinqiao, E-mail: jinqiao1977@163.com [Institute of Pediatrics, Children' s Hospital of Fudan University (China); Sha, Bin [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Zhou, Wenhao, E-mail: zhou_wenhao@yahoo.com.cn [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Yang, Yi [Institute of Pediatrics, Children' s Hospital of Fudan University (China)

    2010-03-26

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  6. Liver transplant outcomes using ideal donation after circulatory death livers are superior to using older donation after brain death donor livers.

    Science.gov (United States)

    Scalea, Joseph R; Redfield, Robert R; Foley, David P

    2016-09-01

    Multiple reports have demonstrated that liver transplantation following donation after circulatory death (DCD) is associated with poorer outcomes when compared with liver transplantation from donation after brain death (DBD) donors. We hypothesized that carefully selected, underutilized DCD livers recovered from younger donors have excellent outcomes. We performed a retrospective study of the United Network for Organ Sharing database to determine graft survivals for patients who received liver transplants from DBD donors of age ≥ 60 years, DBD donors  60 years old. Careful donor organ and recipient selection can lead to excellent results, despite previous reports suggesting otherwise. Increased acceptance of these DCD livers would lead to shorter wait list times and increased national liver transplant rates. Liver Transplantation 22 1197-1204 2016 AASLD.

  7. Brain stem global gene expression profiles in human spina bifida embryos

    Institute of Scientific and Technical Information of China (English)

    Hong Zhao; Xiang Li; Wan-I Lie; Quanren He; Ting Zhang; Xiaoying Zheng; Ran Zhou; Jun Xie

    2011-01-01

    Environmental and genetic factors influence the occurrence of neural tube defects, such as spina bifida.Specific disease expression patterns will help to elucidate the pathogenesis of disease.However, results obtained from animal models, which often exhibit organism specificity, do not fully explain the mechanisms of human spina bifida onset.In the present study, three embryos with a gestational age of approximately 17 weeks and a confirmed diagnosis of spina bifida, as well as 3 age-matched normal embryos, were obtained from abortions.Fetal brain stem tissues were dissected for RNA isolation, and microarray analyses were conducted to examine profiles of gene expression in brain stems of spina bifida and normal embryos using Affymetrix HG-U1 33A 2.0 GeneChip arrays.Of the 14 500 gene transcripts examined, a total of 182 genes exhibited at least 2.5-fold change in expression, including 140 upregulated and 42 downregulated genes.These genes were placed into 19 main functional categories according to the Gene Ontology Consortium database for biological functions.Of the 182 altered genes, approximately 50% were involved in cellular apoptosis, growth, adhesion, cell cycle, stress, DNA replication and repair, signal transduction, nervous system development, oxidoreduction, immune responses, and regulation of gene transcription.Gene expression in multiple biological pathways was altered in the brain stem of human spina bifida embryos.

  8. HTLV-I associated myelopathy with multiple spotty areas in cerebral white matter and brain stem by MRI

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    Hara, Yasuo; Takahashi, Mitsuo; Yoshikawa, Hiroo; Yorifuji, Shirou; Tarui, Seiichiro

    1988-01-01

    A 48-year-old woman was admitted with complaints of urinary incontinence and gait disturbance, both of which had progressed slowly without any sign of remission. Family history was not contributory. Neurologically, extreme spasticity was recoginized in the lower limbs. Babinski sign was positive bilaterally. Flower-like atypical lymphocytes were seen in blood. Positive anti-HTLV-I antibody was confirmed in serum and spinal fluid by western blot. She was diagnosed as having HTLV-I associated myelopathy (HAM). CT reveald calcification in bilateral globus pallidus, and MRI revealed multiple spotty areas in cerebral white matter and brain stem, but no spinal cord lesion was detectable. Electrophysiologically, brain stem auditory evoked potential (BAEP) suggested the presence of bilateral brain stem lesions. Neither median nor posterior tibial nerve somatosensory evoked potentials were evoked, a finding suggesting the existence of spinal cord lesion. In this case, the lesion was not confined to spinal cord, it was also observed in brain stem and cerebral white matter. Such distinct lesions in cerebral white matter and brain stem have not been reported in patients with HAM. It is suggested that HTLV-I is probably associated with cerebral white matter and brain stem.

  9. Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia

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    Corna Melissa F

    2011-07-01

    Full Text Available Abstract Background Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia. Methods Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments. Results Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells. Conclusions We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.

  10. The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation.

    Science.gov (United States)

    Kalisvaart, Marit; de Haan, Jubi E; Hesselink, Dennis A; Polak, Wojciech G; Hansen, Bettina E; IJzermans, Jan N M; Gommers, Diederik; Metselaar, Herold J; de Jonge, Jeroen

    2016-11-19

    Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06-4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.

  11. Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size.

    Science.gov (United States)

    Chen, Jian-Fu; Zhang, Ying; Wilde, Jonathan; Hansen, Kirk C; Lai, Fan; Niswander, Lee

    2014-05-30

    Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly.

  12. Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain

    Science.gov (United States)

    Fierens, Igor; Rocha-Ferreira, Eridan; Hristova, Mariya; Ezzati, Mojgan; Rostami, Jamshid; Alonso-Alconada, Daniel; Chaban, Badr; Hassell, Jane; Fleiss, Bobbi; Gressens, Pierre; Sanders, Robert D.; Robertson, Nicola J.

    2017-01-01

    In a range of animal species, exposure of the brain to general anaesthesia without surgery during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex but include an increase in brain cell death. In humans, attempts to link adverse cognitive development to infantile anaesthesia exposure have yielded ambiguous results. One caveat that may influence the interpretation of human studies is that infants are not exposed to general anaesthesia without surgery, raising the possibility that surgery itself, may contribute to adverse cognitive development. Using piglets, we investigated whether a minor surgical procedure increases cell death and disrupts neuro-developmental and cognitively salient gene transcription in the neonatal brain. We randomly assigned neonatal male piglets to a group who received 6h of 2% isoflurane anaesthesia or a group who received an identical anaesthesia plus 15 mins of surgery designed to replicate an inguinal hernia repair. Compared to anesthesia alone, surgery-induced significant increases in cell death in eight areas of the brain. Using RNAseq data derived from all 12 piglets per group we also identified significant changes in the expression of 181 gene transcripts induced by surgery in the cingulate cortex, pathway analysis of these changes suggests that surgery influences the thrombin, aldosterone, axonal guidance, B cell, ERK-5, eNOS and GABAA signalling pathways. This suggests a number of novel mechanisms by which surgery may influence neural and cognitive development independently or synergistically with the effects of anaesthesia. PMID:28355229

  13. Characteristic of brain perfusion imaging in children brain death patients%儿童脑死亡患者脑血流灌注显像特点

    Institute of Scientific and Technical Information of China (English)

    杨吉刚; 庄红明

    2012-01-01

    Objective To investigate characteristics of brain perfusion imaging of patients with brain death. Methods 77 pediatric patients with clinical suspicion brain death were received brain perfusion imaging, Eventually, 77 patients were died within twenty four hours after last brain perfusion imaging. These data were retrospectively analyzed. Results In the 15 patients (19.5%), the images revealed minimal radioactivity in the brain, which can be seen clearly part of the brain of patients with radioactive distribution. The other patients can be seen a small number of radioactivity distribution. While 62 patients (80.5%) with cerebral perfusion imaging showed brain no radioactive distribution. Conclusion Patients with brain perfusion imaging of the brain no radioactive distribution is the performance of the typical brain-dead, brain no radioactive distribution must not survive. However, the brain radioactivity distribution of patients is not indicative of patient survival.%目的 研究儿童脑死亡患者脑血流灌注显像特点.方法 77例临床怀疑脑死亡的患者行脑血流灌注显像,最终77例患者全部于最后一次脑血流灌注显像后24 h内死亡.本研究回顾性分析脑血流灌注显像的特点.结果 15例(19.5%)患者脑血流灌注显像示脑内可见放射性分布,其中部分患者脑内可见明显放射性分布,其余患者可见少量放射性分布;62例(80.5%)患者脑血流灌注显像示脑内未见放射性分布.临床随访证实77例患者最终全部死亡.结论 脑血流灌注显像示脑内未见放射性分布是典型脑死亡的表现,脑内未见放射性分布的患者一定不能存活,但脑内有放射性分布的患者并不预示患者存活.

  14. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

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    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  15. Analysis of the reports of high-level commissions that have comprehensively reviewed US public policy on brain death.

    Science.gov (United States)

    Kofke, W Andrew

    2014-12-01

    The notion of brain death from its inception has not been uniformly understood with many grisly conceptions of it as it pertains to reliability and to organ donation. Accordingly, the aforementioned recitation of statutes and commission reports has served a useful societal role in addressing controversies and misconceptions while promulgating unifying foundational concepts and guidance in practical translation to clinical practice. There is clearly a consensus that statutory uniformity across jurisdictions is important and that there are two ways to define death. The first is the traditional cardiopulmonary criteria of cessation of cardiac function and breathing. The second is through established procedures to reliably determine the presence of total brain death with the presence of a comatose state which is irreversible. Another common thread through the ethically focused reports has been recognition that organ donation and death are temporally and geographically associated but there is emphasis that the processes of determination of death(by somatic or cerebral criteria) must be logically, ethically, and procedurally separate from the procedures for performing organ harvesting and transplantation.

  16. A narrative review of the empirical evidence on public attitudes on brain death and vital organ transplantation: the need for better data to inform policy.

    Science.gov (United States)

    Shah, Seema K; Kasper, Kenneth; Miller, Franklin G

    2015-04-01

    Vital organ transplantation is premised on 'the dead donor rule': donors must be declared dead according to medical and legal criteria prior to donation. However, it is controversial whether individuals diagnosed as 'brain dead' are really dead in accordance with the established biological conception of death-the irreversible cessation of the functioning of the organism as a whole. A basic understanding of brain death is also relevant for giving valid, informed consent to serve as an organ donor. There is therefore a need for reliable empirical data on public understanding of brain death and vital organ transplantation. We conducted a review of the empirical literature that identified 43 articles with approximately 18,603 study participants. These data demonstrate that participants generally do not understand three key issues: (1) uncontested biological facts about brain death, (2) the legal status of brain death and (3) that organs are procured from brain dead patients while their hearts are still beating and before their removal from ventilators. These data suggest that, despite scholarly claims of widespread public support for organ donation from brain dead patients, the existing data on public attitudes regarding brain death and organ transplantation reflect substantial public confusion. Our review raises questions about the validity of consent for vital organ transplantation and suggests that existing data are of little assistance in developing policy proposals for organ transplantation from brain dead patients. New approaches to rigorous empirical research with educational components and evaluations of understanding are urgently needed.

  17. Strategies for Regenerating Striatal Neurons in the Adult Brain by Using Endogenous Neural Stem Cells

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    Kanako Nakaguchi

    2011-01-01

    Full Text Available Currently, there is no effective treatment for the marked neuronal loss caused by neurodegenerative diseases, such as Huntington's disease (HD or ischemic stroke. However, recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ of the adult mammalian brain, including the human brain. Because some of these new neurons migrate to the injured striatum and differentiate into mature neurons, such new neurons may be able to replace degenerated neurons and improve or repair neurological deficits. To establish a neuroregenerative therapy using this endogenous system, endogenous regulatory mechanisms that can be co-opted for efficient regenerative interventions must be understood, along with any potential drawbacks. Here, we review current knowledge on the generation of new neurons in the adult brain and discuss their potential for use in replacing striatal neurons lost to neurodegenerative diseases, including HD, and to ischemic stroke.

  18. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

    Science.gov (United States)

    Pathak, Sen; Multani, Asha S; Banerji, Pratip; Banerji, Prasanta

    2003-10-01

    Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.

  19. Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

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    Paris Jafari

    Full Text Available Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i 3-OHGA causes the death of astrocytes, (ii deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I.

  20. Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

    Science.gov (United States)

    Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

    2016-04-01

    Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy.

  1. Absence of Doppler signal in transcranial color-coded ultrasonography may be confirmatory for brain death: A case report

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    Mehmet Akif Topçuoğlu

    2015-08-01

    Full Text Available Transcranial Doppler ultrasonography (TCD is a valuable tool for demonstrating cerebral circulatory arrest (CCA in the setting of brain death. Complete reversal of diastolic flow (to-and-fro flow and systolic spikes in bilateral terminal internal carotid arteries and vertebrobasilar circulation are considered as specific sonogram configurations supporting the diagnosis of CCA. Because of the possibility of sonic bone window impermeability, absence of any waveform in TCD is not confirmatory for CCA unless there is documentation of disappearance of a previously well detected signal by the same recording settings. Transcranial color-coded sonography (TCCS with B-mode imaging can reliably detect adequacy of bone windows with clarity contralateral skull and ipsilateral planum temporale visualization. Therefore, absence of detectable intracranial Doppler signal along with available ultrasound window in TCCS can confirm clinical diagnosis of brain death. We herein discuss this entity from the frame of a representative case.

  2. Benefits of combination of electroencephalography, short latency somatosensory evoked potentials, and transcranial Doppler techniques for confirming brain death

    Institute of Scientific and Technical Information of China (English)

    Kang WANG; Yuan YUAN; Zi-qi XU; Xiao-liang WU; Ben-yan LUO

    2008-01-01

    Objective: Optimization of combining electroencephalography (EEG), short latency somatosensory evoked potentials (SLSEP) and transcranial Doppler (TCD) techniques to diagnose brain death. Methods: One hundred and eleven patients (69 males, 42 females) from the major hospitals of Zhejiang Province were examined with portable EEG, SLSEP and TCD devices. Re-examinations occurred ≤12 h later. Results: The first examination revealed that the combination of SLSEP and EEG led to more sensitive diagnoses than the combination of SLSEP and TCD. Re-examination confirmed this and also revealed that the combination of TCD and EEG was the most sensitive. Conclusion: The results show that using multiple techniques to diagnose brain death is superior to using single method, and that the combination of SLSEP and EEG is better than other combinations.

  3. Amelioration of penetrating ballistic-like brain injury induced cognitive deficits after neuronal differentiation of transplanted human neural stem cells.

    Science.gov (United States)

    Spurlock, Markus S; Ahmed, Aminul Islam; Rivera, Karla N; Yokobori, Shoji; Lee, Stephanie W; Sam, Pingdewinde N; Shear, Deborah A; Hefferan, Michael P; Hazel, Thomas G; Johe, Karl K; Gajavelli, Shyam; Tortella, Frank C; Bullock, Ross

    2017-03-01

    Penetrating traumatic brain injury (PTBI) is one of the major cause of death and disability worldwide. Previous studies in penetrating ballistic-like brain injury (PBBI), a PTBI rat model revealed widespread peri-lesional neurodegeneration, similar to that seen in humans following gunshot wound to head, which is unmitigated by any available therapies to date. Therefore, we evaluated human neural stem cell (hNSC) engraftment to putatively exploit the potential of cell therapy that has been seen in other central nervous system injury models. Towards this, green fluorescent protein (GFP) labeled hNSCs (400,000 per animal) were transplanted in immunosuppressed Sprague Dawley (SD), Fisher, and athymic (ATN) PBBI rats one week after injury. Tacrolimus (3mg/kg two days prior to transplantation, then 1mg/kg/day), Methylprednisolone (10mg/kg on day of transplant, 1mg/kg/week thereafter), and Mycophenolate mofetil (30mg/kg/day) for seven days following transplantation were used to confer immunosuppression. Engraftment in SD and ATN was comparable at 8-weeks post transplantation. Evaluation of hNSC differentiation and distribution revealed increased neuronal differentiation of transplanted cells with time. At 16-weeks post-transplantation neither cell proliferation nor glial lineage markers expression was detected. Transplanted cell morphology was similar to neighboring host neurons and there was relatively little migration of cells from the peri-transplant site. By 16 weeks, GFP positive processes extended both rostro-caudally and bilaterally into parenchyma, spreading along host white matter tracts, traversing internal capsule, extending ~13 mm caudally from transplantation site reaching into the brain stem. In a Morris water maze test at 8-weeks post-transplantation, animals with transplants had shorter latency to platform compared to vehicle treated animals. However, weak injury-induced cognitive deficits in the control group at the delayed time point confounded benefits

  4. comparative study on effective factors on consent to organ donation among families of brain death victims in Isfahan, 2013

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    Fereshte Zamani

    2015-05-01

    Full Text Available Introduction: According to the previous studies, several social, cultural, and organizational factors are involved in the decision of families of brain death victims for organ donation. The present study was performed to determine the effective factors in the decision of organ donation among families of brain death victims. Methods: In this descriptive-comparative study data were gathered through a self-made questionnaire. The reliability of questionnaire was determined by calculating Cronbach’s alpha (0.81 and the face and content validity were studied and approved by a number of experts. Statistical population included all family members of brain death victims in Isfahan/Iran during 2012-2013. They were divided into two groups of with and without consent to organ donation. The whole population was considered as the study sample. Data analysis were done through SPSS using independent T-test, ANOVA, and Chi-square tests. Results: According to the present study, age and marital status of the victims have no effect on their families’ consent to organ donation (P> 0.05; but sex, duration of hospitalization in the emergency department, having organ donation card ,and personal opinion of the brain death victim showed significant relationship with consent to organ donation (P< 0.05. Conclusion: Since the rate of awareness, knowledge, and attitude of family members are effective in their decision for organ donation, improving cultural backgrounds required for this decision and increasing awareness and knowledge of people can improve the attitude of people in this regard and facilitate the acceptance of family members

  5. Possibility of influence of midazolam sedation on the diagnosis of brain death: concentrations of active metabolites after cessation of midazolam.

    Science.gov (United States)

    Hirata, Kiyotaka; Matsumoto, Yoshiaki; Kurokawa, Akira; Onda, Miho; Shimizu, Makiko; Fukuoka, Masamichi; Hirano, Masaaki; Yamamoto, Yasuhiro

    2003-09-01

    Midazolam and its active metabolites have a depressant effect on respiration and consciousness level, and therefore their effects should be considered in all patients for whom brain death testing is contemplated. The concentrations of midazolam and its active metabolites were measured in critically ill patients on a ventilator during and after continuous intravenous infusion of midazolam. Three days after cessation of midazolam infusion, the concentrations of midazolam and 1-hydroxymidazolam decreased to below the therapeutic range (100-1000 ng/ml) in all patients, although the concentrations of 1-hydroxymidazolam glucuronide remained extremely high in a patient who showed deteriorating renal function. The concentrations of 1-hydroxymidazolam glucuronide (19,497-29,761 ng/ml) were measured in this patient. When it is impossible to confirm factors consistent with irreversible brain death, such as the lack of cerebral blood flow, until 3 days after cessation of midazolam infusion, monitoring of the concentration of these substances should be carried out in all patients in whom suspicion exists prior to the evaluation of brain death. It is particularly imperative that monitoring of the 1-hydroxymidazolam glucuronide concentration be carried out in patients with poor renal function.

  6. Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients

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    S T Camargos

    2011-01-01

    Full Text Available Machado-Joseph disease, or spinocerebellar ataxia type 3(MJD/SCA3, is the most frequent late onset spinocerebellar ataxia and results from a CAG repeat expansion in the ataxin-3 gene. Previous studies have found correlation between atrophy of cerebellum and brainstem with age and CAG repeats, although no such correlation has been found with disease duration and clinical manifestations. In this study we test the hypothesis that atrophy of cerebellum and brainstem in MJD/SCA3 is related to clinical severity, disease duration and CAG repeat length as well as to other variables such as age and ICARS (International Cooperative Ataxia Rating Scale. Whole brain high resolution MRI and volumetric measurement with cranial volume normalization were obtained from 15 MJD/SCA3 patients and 15 normal, age and sex-matchedcontrols. We applied ICARS and compared the score with volumes and CAG number, disease duration and age. We found significant correlation of both brain stem and cerebellar atrophy with CAG repeat length, age, disease duration and degree of disability. The Spearman rank correlation was stronger with volumetric reduction of the cerebellum than with brain stem. Our data allow us to conclude that volumetric analysis might reveal progressive degeneration after disease onset, which in turn is linked to both age and number of CAG repeat expansions in SCA 3.

  7. Brain vascular pericytes following ischemia have multipotential stem cell activity to differentiate into neural and vascular lineage cells.

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    Nakagomi, Takayuki; Kubo, Shuji; Nakano-Doi, Akiko; Sakuma, Rika; Lu, Shan; Narita, Aya; Kawahara, Maiko; Taguchi, Akihiko; Matsuyama, Tomohiro

    2015-06-01

    Brain vascular pericytes (PCs) are a key component of the blood-brain barrier (BBB)/neurovascular unit, along with neural and endothelial cells. Besides their crucial role in maintaining the BBB, increasing evidence shows that PCs have multipotential stem cell activity. However, their multipotency has not been considered in the pathological brain, such as after an ischemic stroke. Here, we examined whether brain vascular PCs following ischemia (iPCs) have multipotential stem cell activity and differentiate into neural and vascular lineage cells to reconstruct the BBB/neurovascular unit. Using PCs extracted from ischemic regions (iPCs) from mouse brains and human brain PCs cultured under oxygen/glucose deprivation, we show that PCs developed stemness presumably through reprogramming. The iPCs revealed a complex phenotype of angioblasts, in addition to their original mesenchymal properties, and multidifferentiated into cells from both a neural and vascular lineage. These data indicate that under ischemic/hypoxic conditions, PCs can acquire multipotential stem cell activity and can differentiate into major components of the BBB/neurovascular unit. Thus, these findings support the novel concept that iPCs can contribute to both neurogenesis and vasculogenesis at the site of brain injuries.

  8. Stemming the impact of health professional brain drain from Africa: a systemic review of policy options

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    Edward Zimbudzi

    2013-06-01

    Full Text Available Africa has been losing professionally trained health workers who are the core of the health system of this continent for many years. Faced with an increased burden of disease and coupled by a massive exodus of the health workforce, the health systems of many African nations are risking complete paralysis. Several studies have suggested policy options to reduce brain drain from Africa. The purpose of this paper is to review possible policies, which can stem the impact of health professional brain drain from Africa. A systemic literature review was conducted. Cinahl, Science Direct and PubMed databases were searched with the following terms: health professional brain drain from Africa and policies for reducing impact of brain drain from Africa. References were also browsed for relevant articles. A total of 425 articles were available for the study but only 23 articles met the inclusion criteria. The review identified nine policy options, which were being implemented in Africa, but the most common was task shifting which had success in several African countries. This review has demonstrated that there is considerable consensus on task shifting as the most appropriate and sustainable policy option for reducing the impact of health professional brain drain from Africa.

  9. Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt

    Directory of Open Access Journals (Sweden)

    Kuo Selena Z

    2012-11-01

    Full Text Available Abstract Background Cancer stem cells (CSC are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC stem cells. Methods MTS and TUNEL assays were used to study cell proliferation and apoptosis as a function of salinomycin exposure in JLO-1, a putative HNSCC stem cell culture. MTS and trypan blue dye exclusion assays were performed to investigate potential drug interactions between salinomycin and cisplatin or paclitaxel. Stem cell-like phenotype was measured by mRNA expression of stem cell markers, sphere-forming capacity, and matrigel invasion assays. Immunoblotting was also used to determine expression of epithelial-mesenchymal transition (EMT markers and Akt phosphorylation. Arrays by Illumina, Inc. were used to profile microRNA expression as a function of salinomycin dose. Results In putative HNSCC stem cells, salinomycin was found to significantly inhibit cell viability, induce a 71.5% increase in levels of apoptosis, elevate the Bax/Bcl-2 ratio, and work synergistically with cisplatin and paclitaxel in inducing cell death. It was observed that salinomycin significantly inhibited sphere forming-capability and repressed the expression of CD44 and BMI-1 by 3.2-fold and 6.2-fold, respectively. Furthermore, salinomycin reduced invasion of HNSCC stem cells by 2.1 fold. Contrary to expectations, salinomycin induced the expression of EMT markers Snail, vimentin, and Zeb-1, decreased expression of E-cadherin, and also induced phosphorylation of Akt and its downstream targets GSK3-β and mTOR. Conclusions These results demonstrate that in HNSCC cancer stem cells, salinomycin can cause cell death and

  10. Activation of endogenous neural stem cells in experimental intracerebral hemorrhagic rat brains

    Institute of Scientific and Technical Information of China (English)

    唐涛; 黎杏群; 武衡; 罗杰坤; 张花先; 罗团连

    2004-01-01

    Background Many researchers suggest that adult mammalian central nervous system (CNS) is incapable of completing self-repair or regeneration. And there are accumulating lines of evidence which suggest that endogenous neural stem cells (NSCs) are activated in many pathological conditions, including stroke in the past decades, which might partly account for rehabilitation afterwards. In this study, we investigated whether there was endogenous neural stem cell activation in intracerebral hemorrhagic (ICH) rat brains.Methods After ICH induction by stereotactical injection of collagenase type Ⅶ into globus pallidus, 5-Bromo-2 Deoxyuridine (BrdU) was administered intraperitoneally to label newborn cells. Immunohistochemical method was used to detect Nestin, a marker for neural stem cells, and BrdU.Results Nestin-positive or BrdU-Labeled cells were predominantly located at 2 sites: basal ganglion around hemotoma, ependyma and nearby subventricular zone (SVZ). No positive cells for the 2 markers were found in the 2 sites of normal control group and sham group, as well as in non-leisoned parenchyma, both hippocampi and olfactory bulbs in the 4 groups. Nestin+ cells presented 4 types of morphology, and BrdU+ nucleus were polymorphologic. Postive cell counting around hemotoma showed that at day 2, Nestin+ cells were seen around hemotoma in model group , the number of which increased at day 4, day 7(P<0.01), peaked at day 14(P<0.05), and reduced significantly by day 28(P<0.01).Conclusion Endogenous neural stem cells were activated in experimental intracerebral hemorrhagic rat brains.

  11. Comparitive Study Between Cnventional and Hyperfractionaltion Radiation Therapy for The Treatment of Brain Stem Tumors

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    Laila Fares * (MD, Mamdouh Salama** (MD Manal Moawad

    2001-06-01

    Full Text Available Brain stem tumors are special challenge because primarily of their location and the neurologic effect caused by these groups of tumors (Paul 1997. Radiation therapy improves survival for brain stem tumors and stabilizes or reverses neurologic dysfunction in 75-90% of patients. The main domain of applicability of hyperfractionation would be in tumor sites where the dose limiting tissue is late reacting and whose effective control requires the delivery of doses beyond tolerance (Awwad, 1990, hence the rationale for the use of hyperfractionation in brain stem lesions. The purpose of this work is to find out the best radiation protocol in this group of patients comparing conventional fractionation and hyperafractionation. This study included 46 patients which brainstem tumors treated in Radiation Oncology and Neurosurgery Departments Ain Shams University between February 1998 and May 2000. These patients had been randomly distributed in 2 groups A and B. The first group treated by conventional radiotherapy protocol and the second group treated by hyperfractionation radiation protocol. By the end of the study, the median over all survival and median time for disease progression were calculated for each group. Age, neurologic status at presentation and anatomical location were significant prognostic factors. By the end of this study clicinal evalualion had no significant difference between both groups but the median over all survival for the two groups was 10.5 months, the median survival for group A was 9.4 months and that for group B was 11.5 months which was statistically significant P < 0.02. On the other hand the percentage of patient with one year survival for group A & B (22%, 32% respectively. The rate of acute (early reaction of radiation is slightly higher in hyperfracticmaticm than conventional fractionation but the late reactions occur with same frequency with both regimens.

  12. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI.

    Science.gov (United States)

    Jubault, Thomas; Brambati, Simona M; Degroot, Clotilde; Kullmann, Benoît; Strafella, Antonio P; Lafontaine, Anne-Louise; Chouinard, Sylvain; Monchi, Oury

    2009-12-10

    Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia). Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC) matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution) and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3) in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.

  13. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI.

    Directory of Open Access Journals (Sweden)

    Thomas Jubault

    Full Text Available Idiopathic Parkinson's disease (PD is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia. Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3 in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.

  14. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

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    Xianchao Li; Wensheng Hou; Xiaoying Wu; Wei Jiang; Haiyan Chen; Nong Xiao; Ping Zhou

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hy-poxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efifciencies are relatively low. Red or near-infrared light from 600-1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migra-tion and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2, an increasing number of green lfuorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 106 bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2 for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental ifndings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypox-ic-ischemic brain damage.

  15. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment.

    Science.gov (United States)

    Li, Xianchao; Hou, Wensheng; Wu, Xiaoying; Jiang, Wei; Chen, Haiyan; Xiao, Nong; Zhou, Ping

    2014-02-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600-1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2), an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 10(6) bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2) for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage.

  16. Thermal treatment of bentonite reduces aflatoxin b1 adsorption and affects stem cell death.

    Science.gov (United States)

    Nones, Janaína; Nones, Jader; Riella, Humberto Gracher; Poli, Anicleto; Trentin, Andrea Gonçalves; Kuhnen, Nivaldo Cabral

    2015-10-01

    Bentonites are clays that highly adsorb aflatoxin B1 (AFB1) and, therefore, protect human and animal cells from damage. We have recently demonstrated that bentonite protects the neural crest (NC) stem cells from the toxicity of AFB1. Its protective effects are due to the physico-chemical properties and chemical composition altered by heat treatment. The aim of this study is to prepare and characterize the natural and thermal treatments (125 to 1000 °C) of bentonite from Criciúma, Santa Catarina, Brazil and to investigate their effects in the AFB1 adsorption and in NC cell viability after challenging with AFB1. The displacement of water and mineralogical phases transformations were observed after the thermal treatments. Kaolinite disappeared at 500 °C and muscovite and montmorillonite at 1000 °C. Slight changes in morphology, chemical composition, and density of bentonite were observed. The adsorptive capacity of the bentonite particles progressively reduced with the increase in temperature. The observed alterations in the structure of bentonite suggest that the heat treatments influence its interlayer distance and also its adsorptive capacity. Therefore, bentonite, even after the thermal treatment (125 to 1000 °C), is able to increase the viability of NC stem cells previously treated with AFB1. Our results demonstrate the effectiveness of bentonite in preventing the toxic effects of AFB1.

  17. Science Letters: Brain natriuretic peptide: A potential indicator of cardiomyogenesis after autologous mesenchymal stem cell transplantation?

    Institute of Scientific and Technical Information of China (English)

    LI Nan; WANG Jian-an

    2006-01-01

    We observed in a pilot study that there was a transient elevation of brain natriuretic peptide (BNP) level shortly after the transplantation in the patient with ischemic heart failure, which is unexplainable by the simultaneous increase of the cardiac output and six-minute walk distance. Similar findings were observed in the phase I trial. We postulated on the basis of the finding of Fukuda in vitro that this transient elevation of BNP level against the improvement of cardiac function and exercise capacity might indicate cardiomyogenesis in patients after mesenchymal stem cell transplantation. Further study is warranted to verify the hypothesis.

  18. Reelin signaling in the migration of ventral brain stem and spinal cord neurons

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    Sandra eBlaess

    2016-03-01

    Full Text Available The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

  19. Influence of hyperbaric oxygen on the differentiation of hypoxic/ischemic brain-derived neural stem cells

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    Zhengrong Peng; Sue Wang; Pingtian Xiao

    2009-01-01

    BACKGROUND: It has been previously shown that hyperbaric oxygen may promote proliferation of neural stem cells and reduce death of endogenous neural stem cells (NSCs).OBJECTIVE: To explore the effects of hyperbaric oxygen on the differentiation of hypoxic/ischemic brain-derived NSCs into neuron-like cells and compare with high-concentration oxygen and high pressure.DESIGN, TIME AND SETTING: An in vitro contrast study, performed at Laboratory of Neurology,Central South University between January and May 2006.MATERIALS: A hyperbaric oxygen chamber (YLC 0.5/1A) was provided by Wuhan Shipping Design Research Institute; mouse anti-rat microtubute-associated protein 2 monoclonal antibody by Jingmei Company, Beijing; mouse anti-rat glial fibrillary acidic protein monoclonal antibody by Neo Markers,USA; mouse anti-rat galactocerebroside monoclonal antibody by Santa Cruz Biotechnology Inc.,USA; and goat anti-mouse fluorescein isothiocyanate-labeled secondary antibody by Wuhan Boster Bioengineering Co., Ltd., China.METHODS: Brain-derived NSCs isolated from brain tissues of neonatal Sprague Dawiey rats werecloned and passaged, and assigned into five groups: normal control, model, high-concentration oxygen, high pressure, and hyperbaric oxygen groups. Cells in the four groups, excluding the normal control group, were incubated in serum-containing DMEM/F12 culture medium. Hypoxic/ischemic models of NSCs were established in an incubator comprising 93% N2, 5% CO2, and 2% O2.Thereafter, cells were continuously cultured as follows: compressed air (0.2 MPa, 1 hour, once a day)in the high pressure group, compressed air+a minimum of 80% O2 in the hyperbaric oxygen group,and a minimum of 80% O2 in the high-concentration oxygen group. Cells in the normal control and model groups were cultured as normal.MAIN OUTCOME MEASURES: At day 7 after culture, glial fibrillary acidic protein,microtubule-associated protein 2, and galactocerebroside immunofluorescence staining were examined to

  20. Stem cell-based delivery of brain-derived neurotrophic factor gene in the rat retina.

    Science.gov (United States)

    Park, Hae-Young Lopilly; Kim, Jie Hyun; Sun Kim, Hwa; Park, Chan Kee

    2012-08-21

    As an alternative to a viral vector, the application of stem cells to transfer specific genes is under investigation in various organs. Using this strategy may provide more effective method to supply neurotrophic factor to the neurodegenerative diseases caused by neurotrophic factor deprivation. This study investigated the possibility and efficacy of stem cell-based delivery of the brain-derived neurotrophic factor (BDNF) gene to rat retina. Rat BDNF cDNA was transduced into rat bone marrow mesenchymal stem cells (rMSCs) using a retroviral vector. Its incorporation into the experimental rat retina and the expression of BDNF after intravitreal injection or subretinal injection were detected by real-time PCR, western blot analysis, and immunohistochemical staining. For the incorporated rMSCs, retinal-specific marker staining was performed to investigate the changes in morphology and the characteristics of the stem cells. Transduction of the rMSCs by retrovirus was effective, and the transduced rMSCs expressed high levels of the BDNF gene and protein. The subretinal injection of rMSCs produced rMSC migration and incorporation into the rat retina (about 15.7% incorporation rate), and retinal BDNF mRNA and protein expression was increased at 4 weeks after transplantation. When subretinal injection of rMSCs was applied to axotomized rat retina, it significantly increased the expression of BDNF until 4 weeks after transplantation. Some of the transplanted rMSCs exhibited morphological changes, but the retinal-specific marker stain was not sufficient to indicate whether neuronal differentiation had occurred. Using mesenchymal stem cells to deliver the BDNF gene to the retina may provide new treatment for glaucoma.

  1. Research progress in brain tumor stem cells%脑肿瘤干细胞的研究现状

    Institute of Scientific and Technical Information of China (English)

    王欣欣; 刘季平

    2012-01-01

    BACKGROUND: Research in recent years has discovered some stem cell-like cells exist in brain tumors, which have theproperties of endless cell proliferation, uncontrolled self-renewal and multi-directional differentiation, and they are called as braintumor stem cells. Brain tumor stem cells play a key role in the progress of tumorigenesis, growth, invasion, metastasis andrecurrence.OBJECTIVE: To conclude and explore the current studies on brain tumor stem cells.METHODS: A computer-based search of Pubmed Database was performed to retrieve relevant articles about brain tumor andbrain tumor stem cells published from January 1977 to July 2011. Books on stem cells and brain tumor stem cells were alsoretrieved. The data were selected primarily, and 32 articles related to brain tumor stem cells were selected.RESULTS AND CONCLUSION: Brain tumor stem cells exist in malignant brain tumor, and they are the origin of the occurrence,development, metastasis and recurrence of malignant brain tumor. Brain tumor stem cells express CD133, Nestin protein andABC transporter in malignant brain tumors. Recently, a simple method has been obtained to isolate brain tumor stem cells. Theproportion of CD133 positive tumor stem cells is positively correlated with the severity of malignant brain tumors, which can beused as a diagnostic indicator of prognosis.%背景:在脑肿瘤中存在一种具有自我更新、无限增殖与多向分化能力的细胞,即脑肿瘤干细胞.脑肿瘤干细胞被认为是脑肿瘤发生、发展、转移与复发的根源.目的:总结和探讨脑肿瘤干细胞的研究现状.方法:以"脑肿瘤、脑肿瘤干细胞"为检索词,应该计算机检索Pubmed 数据库1977-01/2011-07的相关文章,并查阅与干细胞及脑肿瘤干细胞实验有关的书籍,对资料进行初审,选取符合要求的有关文章共32 篇.结果与结论:在恶性脑肿瘤中存在脑肿瘤干细胞.脑肿瘤干细胞是恶性脑肿瘤发生、发展、转移及复发的

  2. Activin and TGF-β effects on brain development and neural stem cells.

    Science.gov (United States)

    Rodríguez-Martínez, Griselda; Velasco, Iván

    2012-11-01

    Transforming Growth Factor-β (TGF-β) family members are ubiquitously expressed, participating in the regulation of many processes in different cell types both in embryonic and adult stages. Several members of this family, including Activins, TGF-β1-3 and Nodal, have been implicated in the development and maintenance of various organs, in which stem cells play important roles. Although TGF-β was initially considered an injury-related cytokine, it became clear that not only TGF-β, but other members of this family, play critical roles in morphogenesis and cell lineage specification. During brain development, Activin and TGF-βs as well as their cognate receptors, are expressed in different patterns. The roles of Activin and TGF-β during CNS development are sometimes contradictory, because these proteins present different actions depending on the cell type and the context. The aim of this review is to summarize current information on the actions of TGF-β members during developing brain, and also on Neural Stem/Progenitor Cells (NSPC). We focus on the TGF-β subgroup, specifically on the effects of TGF-β1 and Activin A. In the first section we describe the main characteristics of the ligands, its receptors as well as the proteins and mechanisms involved in signaling. Next, we discuss the main advances concerning TGF-β1 and Activin actions during brain development and their roles in NSPC fate decision and neuroprotection both in vitro and in vivo. The emerging picture from these studies suggests that these growth factors can be used to manipulate neurogenesis and might help to achieve restoration after brain deterioration.

  3. Occurrence of specific environmental risk factors in brain tissues of sudden infant death and sudden intrauterine unexpected death victims assessed with gas chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Termopoli, Veronica; Famiglini, Giorgio; Palma, Pierangela; Magrini, Laura; Cappiello, Achille

    2015-03-01

    Sudden infant death syndrome (SIDS) and sudden intrauterine unexpected death syndrome (SIUDS) are an unresolved teaser in the social-medical and health setting of modern medicine and are the result of multifactorial interactions. Recently, prenatal exposure to environmental contaminants has been associated with negative pregnancy outcomes, and verification of their presence in fetal and newborn tissues is of crucial importance. A gas chromatography-tandem mass spectrometry (MS/MS) method, using a triple quadrupole analyzer, is proposed to assess the presence of 20 organochlorine pesticides, two organophosphate pesticides, one carbamate (boscalid), and a phenol (bisphenol A) in human brain tissues. Samples were collected during autopsies of infants and fetuses that died suddenly without any evident cause. The method involves a liquid-solid extraction using n-hexane as the extraction solvent. The extracts were purified with Florisil cartridges prior to the final determination. Recovery experiments using lamb brain spiked at three different concentrations in the range of 1-50 ng g(-1) were performed, with recoveries ranging from 79 to 106%. Intraday and interday repeatability were evaluated, and relative standard deviations lower than 10% and 18%, respectively, were obtained. The selectivity and sensitivity achieved in multiple reaction monitoring mode allowed us to achieve quantification and confirmation in a real matrix at levels as low as 0.2-0.6 ng g(-1). Two MS/MS transitions were acquired for each analyte, using the Q/q ratio as the confirmatory parameter. This method was applied to the analysis of 14 cerebral cortex samples (ten SIUDS and four SIDS cases), and confirmed the presence of several selected compounds.

  4. Brain components

    Science.gov (United States)

    ... can make complex movements without thinking. The brain stem connects the brain with the spinal cord and is composed of ... structures: the midbrain, pons, and medulla oblongata. The brain stem provides us with automatic functions that are necessary ...

  5. Carbon monoxide inhalation ameliorates conditions of lung grafts from rat brain death donors

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hua-cheng; DING Wen-gang; CUI Xiao-guang; PAN Peng; ZHANG Bing; LI Wen-zhi

    2008-01-01

    Background Successful lung transplantation has been limited by the scarcity of donors. Brain death (BD) donors are major source of lung transplantation. Whereas BD process induces acute lung injury and aggravates lung ischemia reperfusion injury. Carbon monoxide (CO) inhalation at 50-500 parts per million (ppm) can ameliorate lung injury in several models. We examined in rats whether CO inhalation in BD donor would show favorable effects on lung grafts.Methods Rats were randomly divided into 4 groups. In sham group, donor rats received insertion of a balloon catheter into the cranial cavity, but the balloon was not inflated. In BD-only group, donor rats were ventilated with 40% oxygen after BD confirmation. In BD+CO250 and BD+CO500 groups, donor rats inhaled, after BD confirmation, 250 ppm or 500 ppm CO for 120 minutes prior to lung procurement, and orthotopic lung transplantation was performed. The rats were sacrificed 120 minutes after the lung transplantation by exsanguination, and their blood and lung graft samples were obtained. A total of 8 rats fulfilling the criteria were included in each group.Results The inhalation decreased the severity of lung injury in grafts from BD donors checked by histological examination. CO pretreatment reversed the aggravation of PaO2/FiO2 in recipients from BD donors. The CO inhalation down-regulated pro-inflammatory cytokines (TNF-α, IL-6) along with the increase of anti-inflammatory cytokine (IL-10) in recipient serum, and inhibited the activity of myeloperoxidase in grafts tissue. The inhalation significantly decreased cell apoptosis in lung grafts, inhibiting mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and caspase-3 in lung grafts. Further, the inhalation activated phosphorylation of p38 expression and inhibited phosphorylation of anti-extraceUular signal-regulated kinase (ERK) expression in lung grafts. The effects of CO at 500 ppm were greater than those at 250 ppm.Conclusions CO exerts

  6. Neural stem cell-based dual suicide gene delivery for metastatic brain tumors.

    Science.gov (United States)

    Wang, C; Natsume, A; Lee, H J; Motomura, K; Nishimira, Y; Ohno, M; Ito, M; Kinjo, S; Momota, H; Iwami, K; Ohka, F; Wakabayashi, T; Kim, S U

    2012-11-01

    In our previous works, we demonstrated that human neural stem cells (NSCs) transduced with the cytosine deaminase (CD) gene showed remarkable 'bystander killer effect' on glioma and medulloblastoma cells after administration of the prodrug 5-fluorocytosine (5-FC). In addition, herpes simplex virus thymidine kinase (TK) is a widely studied enzyme used for suicide gene strategies, for which the prodrug is ganciclovir (GCV). To apply this strategy to brain metastasis treatment, we established here a human NSC line (F3.CD-TK) expressing the dual suicide genes CD and TK. We examined whether F3.CD-TK cells intensified the antitumor effect on lung cancer brain metastases. In vitro studies showed that F3.CD-TK cells exerted a marked bystander effect on human lung cancer cells after treatment with 5-FC and GCV. In a novel experimental brain metastases model, intravenously administered F3 cells migrated near lung cancer metastatic lesions, which were induced by the injection of lung cancer cells via the intracarotid artery. More importantly, F3.CD-TK cells in the presence of prodrugs 5-FC and GCV decreased tumor size and considerably prolonged animal survival. The results of the present study indicate that the dual suicide gene-engineered, NSC-based treatment strategy might offer a new promising therapeutic modality for brain metastases.

  7. Injection of SDF-1 loaded nanoparticles following traumatic brain injury stimulates neural stem cell recruitment.

    Science.gov (United States)

    Zamproni, Laura N; Mundim, Mayara V; Porcionatto, Marimelia A; des Rieux, Anne

    2017-03-15

    Recruiting neural stem cell (NSC) at the lesion site is essential for central nervous system repair. This process could be triggered by the local delivery of the chemokine SDF-1. We compared two PLGA formulations for local brain SDF-1 delivery: SDF-1 loaded microspheres (MS) and SDF-1 loaded nanoparticles (NP). Both formulations were able to encapsulate more than 80% of SDF-1 but presented different release profiles, with 100% of SDF-1 released after 6days for the MS and with 25% of SDF-1 released after 2 weeks for NP. SDF-1 bioactivity was demonstrated by a chemotactic assay. When injected in mouse brain after traumatic brain injury, only SDF-1 nanoparticles induced NSC migration to the damage area. More neuroblasts (DCX+ cells) could be visualized around the lesions treated with NP SDF-1 compared to the other conditions. Rostral migratory stream destabilization with massive migration of DCX+ cell toward the perilesional area was observed 2 weeks after NP SDF-1 injection. Local injection of SDF-1-loaded nanoparticles induces recruitment of NSC and could be promising for brain injury lesion.

  8. An international comparison of the effect of policy shifts to organ donation following cardiocirculatory death (DCD) on donation rates after brain death (DBD) and transplantation rates.

    Science.gov (United States)

    Bendorf, Aric; Kelly, Patrick J; Kerridge, Ian H; McCaughan, Geoffrey W; Myerson, Brian; Stewart, Cameron; Pussell, Bruce A

    2013-01-01

    During the past decade an increasing number of countries have adopted policies that emphasize donation after cardiocirculatory death (DCD) in an attempt to address the widening gap between the demand for transplantable organs and the availability of organs from donation after brain death (DBD) donors. In order to examine how these policy shifts have affected overall deceased organ donor (DD) and DBD rates, we analyzed deceased donation rates from 82 countries from 2000-2010. On average, overall DD, DBD and DCD rates have increased over time, with the proportion of DCD increasing 0.3% per year (p = 0.01). Countries with higher DCD rates have, on average, lower DBD rates. For every one-per million population (pmp) increase in the DCD rate, the average DBD rate decreased by 1.02 pmp (95% CI: 0.73, 1.32; pDBD donors with 1.51 less transplants per DCD compared to DBD (95% CI: 1.23, 1.79; pDBD rates, the significant correlation between higher DCD and lower DBD rates coupled with the reduced number of organs transplanted per DCD donor suggests that a national policy focus on DCD may lead to an overall reduction in the number of transplants performed.

  9. Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation.

    Science.gov (United States)

    Hrydziuszko, Olga; Perera, M Thamara P R; Laing, Richard; Kirwan, Jennifer; Silva, Michael A; Richards, Douglas A; Murphy, Nick; Mirza, Darius F; Viant, Mark R

    2016-01-01

    Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations.

  10. A Comparison of Request Process and Outcomes in Donation After Cardiac Death and Donation After Brain Death: Results From a National Study.

    Science.gov (United States)

    Siminoff, L A; Alolod, G P; Wilson-Genderson, M; Yuen, E Y N; Traino, H M

    2016-10-18

    Available literature points to healthcare providers' discomfort with donation after cardiac death (DCD) and their perception of public reluctance toward the procedure. Using a national sample, we report on the communication content of actual DCD and donation after brain death (DBD) approaches by organ procurement organization (OPO) requesters and compare family decision makers' (FDMs') experiences of both modalities. We recruited 1601 FDMs using a validated protocol; 347 (21.7%) were of potential DCD donors. Semistructured telephone interviews yielded FDMs' sociodemographic data, donation attitudes, assessment of approach, final outcomes, and substantiating reasons. Initial analysis consisted of bivariate analyses. Multilevel mixture models compared groups representing authorization outcome and DCD/DBD status. No significant differences in family authorization were found between DCD and DBD cases. Statistically significant associations were found between sociodemographic characteristics and authorization, with white FDMs more likely to authorize DCD or DBD than black FDMs. FDMs of both modalities had similar evaluations of requester skills, topics discussed, satisfaction, and refusal reasons. The findings suggest that the DCD/DBD distinction may not be notable to families. We recommend the use of similar approach strategies and communication skills and the development of education campaigns about the public's acceptance of DCD.

  11. Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation

    Science.gov (United States)

    Laing, Richard; Kirwan, Jennifer; Silva, Michael A.; Richards, Douglas A.; Murphy, Nick; Mirza, Darius F.; Viant, Mark R.

    2016-01-01

    Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations. PMID:27835640

  12. An international comparison of the effect of policy shifts to organ donation following cardiocirculatory death (DCD on donation rates after brain death (DBD and transplantation rates.

    Directory of Open Access Journals (Sweden)

    Aric Bendorf

    Full Text Available During the past decade an increasing number of countries have adopted policies that emphasize donation after cardiocirculatory death (DCD in an attempt to address the widening gap between the demand for transplantable organs and the availability of organs from donation after brain death (DBD donors. In order to examine how these policy shifts have affected overall deceased organ donor (DD and DBD rates, we analyzed deceased donation rates from 82 countries from 2000-2010. On average, overall DD, DBD and DCD rates have increased over time, with the proportion of DCD increasing 0.3% per year (p = 0.01. Countries with higher DCD rates have, on average, lower DBD rates. For every one-per million population (pmp increase in the DCD rate, the average DBD rate decreased by 1.02 pmp (95% CI: 0.73, 1.32; p<0.0001. We also found that the number of organs transplanted per donor was significantly lower in DCD when compared to DBD donors with 1.51 less transplants per DCD compared to DBD (95% CI: 1.23, 1.79; p<0.001. Whilst the results do not infer a causal relationship between increased DCD and decreased DBD rates, the significant correlation between higher DCD and lower DBD rates coupled with the reduced number of organs transplanted per DCD donor suggests that a national policy focus on DCD may lead to an overall reduction in the number of transplants performed.

  13. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Janel E. Le Belle

    2014-11-01

    Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  14. Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells.

    Science.gov (United States)

    Le Belle, Janel E; Sperry, Jantzen; Ngo, Amy; Ghochani, Yasmin; Laks, Dan R; López-Aranda, Manuel; Silva, Alcino J; Kornblum, Harley I

    2014-11-11

    A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  15. The Small-Molecule TrkB Agonist 7, 8-Dihydroxyflavone Decreases Hippocampal Newborn Neuron Death After Traumatic Brain Injury.

    Science.gov (United States)

    Chen, Liang; Gao, Xiang; Zhao, Shu; Hu, Weipeng; Chen, Jinhui

    2015-06-01

    Previous studies in rodents have shown that after a moderate traumatic brain injury (TBI) with a controlled cortical impact (CCI) device, the adult-born immature granular neurons in the dentate gyrus are the most vulnerable cell type in the hippocampus. There is no effective approach for preventing immature neuron death after TBI. We found that tyrosine-related kinase B (TrkB), a receptor of brain-derived neurotrophic factor (BDNF), is highly expressed in adult-born immature neurons. We determined that the small molecule imitating BDNF, 7, 8-dihydroxyflavone (DHF), increased phosphorylation of TrkB in immature neurons both in vitro and in vivo. Pretreatment with DHF protected immature neurons from excitotoxicity-mediated death in vitro, and systemic administration of DHF before moderate CCI injury reduced the death of adult-born immature neurons in the hippocampus 24 hours after injury. By contrast, inhibiting BDNF signaling using the TrkB antagonist ANA12 attenuated the neuroprotective effects of DHF. These data indicate that DHF may be a promising chemical compound that promotes immature neuron survival after TBI through activation of the BDNF signaling pathway.

  16. Region-specific vulnerability to endoplasmic reticulum stress-induced neuronal death in rat brain after status epilepticus

    Indian Academy of Sciences (India)

    Jing Chen; Hu Guo; Guo Zheng; Zhong-Nan Shi

    2013-12-01

    We sought to clarify the involvement and the intra-cerebral distribution variability of C/EBP homologous protein (CHOP), a representative molecule related to endoplasmic reticulum (ER) stress-induced cell death signalling pathways, in neuronal death resulting from status epilepticus in rats. The expression patterns of CHOP and glucose-regulated protein (GRP) 78, a good marker of ER stress, were assessed by Western blotting, real-time PCR, Hoechst and immunohistochemistry in the hippocampus, cortex and striatum on a status epilepticus (SE) model. Double-fluorescent staining of CHOP and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labelling (TUNEL) method were performed to clarify the involvement of CHOP in cell death. SE resulted in a time-dependent increase in the expression of GRP78 and CHOP. The expression of GRP78 protein was increased at 3, 6 and 12 h after SE and no brain region variability was found. The expression of CHOP protein was also increased, reached its peak at 24 h and remained high at 48 h. CHOP protein expression, however, showed brain region variability with highest expression noted in the hippocampus followed by the striatum, and lowest in the cortex. The up-regulation of CHOP occurring at the transcriptional level was demonstrated by real-time PCR. Double fluorescence showed that CHOP expression strongly correlated with neurons undergoing apoptosis. The results indicated that SE compromises the function of the ER and that the hippocampus is more vulnerable than the cortex and the striatum.

  17. In vivo imaging of endogenous neural stem cells in theadult brain

    Institute of Scientific and Technical Information of China (English)

    Maria Adele Rueger; Michael Schroeter

    2015-01-01

    The discovery of endogenous neural stem cells (eNSCs) inthe adult mammalian brain with their ability to self-renewand differentiate into functional neurons, astrocytes andoligodendrocytes has raised the hope for novel therapiesof neurological diseases. Experimentally, those eNSCscan be mobilized in vivo , enhancing regeneration andaccelerating functional recovery after, e.g., focal cerebralischemia, thus constituting a most promising approachin stem cell research. In order to translate those currentexperimental approaches into a clinical setting in thefuture, non-invasive imaging methods are required tomonitor eNSC activation in a longitudinal and intraindividualmanner. As yet, imaging protocols to assesseNSC mobilization non-invasively in the live brain remainscarce, but considerable progress has been made inthis field in recent years. This review summarizes anddiscusses the current imaging modalities suitable tomonitor eNSCs in individual experimental animals overtime, including optical imaging, magnetic resonancetomography and-spectroscopy, as well as positronemission tomography (PET). Special emphasis is puton the potential of each imaging method for a possibleclinical translation, and on the specificity of the signalobtained. PET-imaging with the radiotracer 3'-deoxy-3'-[18F]fluoro-L-thymidine in particular constitutes amodality with excellent potential for clinical translationbut low specificity; however, concomitant imaging ofneuroinflammation is feasible and increases its specificity.The non-invasive imaging strategies presented here allowfor the exploitation of novel treatment strategies basedupon the regenerative potential of eNSCs, and will helpto facilitate a translation into the clinical setting.

  18. Development and modulation of intrinsic membrane properties control the temporal precision of auditory brain stem neurons.

    Science.gov (United States)

    Franzen, Delwen L; Gleiss, Sarah A; Berger, Christina; Kümpfbeck, Franziska S; Ammer, Julian J; Felmy, Felix

    2015-01-15

    Passive and active membrane properties determine the voltage responses of neurons. Within the auditory brain stem, refinements in these intrinsic properties during late postnatal development usually generate short integration times and precise action-potential generation. This developmentally acquired temporal precision is crucial for auditory signal processing. How the interactions of these intrinsic properties develop in concert to enable auditory neurons to transfer information with high temporal precision has not yet been elucidated in detail. Here, we show how the developmental interaction of intrinsic membrane parameters generates high firing precision. We performed in vitro recordings from neurons of postnatal days 9-28 in the ventral nucleus of the lateral lemniscus of Mongolian gerbils, an auditory brain stem structure that converts excitatory to inhibitory information with high temporal precision. During this developmental period, the input resistance and capacitance decrease, and action potentials acquire faster kinetics and enhanced precision. Depending on the stimulation time course, the input resistance and capacitance contribute differentially to action-potential thresholds. The decrease in input resistance, however, is sufficient to explain the enhanced action-potential precision. Alterations in passive membrane properties also interact with a developmental change in potassium currents to generate the emergence of the mature firing pattern, characteristic of coincidence-detector neurons. Cholinergic receptor-mediated depolarizations further modulate this intrinsic excitability profile by eliciting changes in the threshold and firing pattern, irrespective of the developmental stage. Thus our findings reveal how intrinsic membrane properties interact developmentally to promote temporally precise information processing.

  19. Acoustic emissions from the inner ear and brain stem responses in type 2 diabetics

    Directory of Open Access Journals (Sweden)

    Jabbari Moghaddam Y

    2011-12-01

    Full Text Available Yalda Jabbari MoghaddamDepartment of Otolaryngology, Head and Neck Surgery, Tabriz University of Medical Sciences, Tabriz, IranBackground: The purpose of this study was to evaluate the auditory brain stem response (ABR and acoustic emissions of the inner ear (OAE in middle-aged type 2 diabetics.Methods: Fifty type 2 diabetic and nondiabetic patients aged 40–50 years and attending the Tabriz Medical University outpatient clinics were recruited for this study during 2009–2010. All ABR and OAE procedures were implemented by an audiometrist. The relationship between ABR and OAE findings and demographic, laboratory, and clinical characteristics was investigated.Results: Fifty patients (34 female and 16 male of average age 45.7 ± 3.0 years were entered into the study. In the type 2 diabetic group, disordered ABR was found in at least one ear in 8% of cases and disordered OAE was recorded in at least one ear in 16% of cases, with no significant difference between the diabetic and nondiabetic groups. Mean age, duration of diabetes, serum HbA1c levels, and prevalence of female gender were higher in the diabetic group.Conclusion: According to our findings, the prevalence of ABR and OAE is not significantly different between type 2 diabetics and nondiabetics.Keywords: sensorineural hearing loss, diabetes, auditory brain stem response, otoacoustic emission

  20. Morphological and histochemical changes in the brain stem in case of experimental hemispheric intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    S. I. Tertishniy

    2015-10-01

    Full Text Available Aim. Investigation of the extent of morphological changes and activity of biogenic amines (according to the intensity of luminescence in the neurons of the brain stem in intracerebral hemorrhage (ICH. Methods and results. ICH was designed on 29 white rats of Vistar line by the administration of autologous blood in the cerebral hemisphere. It was revealed that increased luminescence intensity by 18.4±5.5% was registered in monoaminergic neurons in 1–6 hours after experimental ICH. After 12 hours – 1 day development of dislocation syndrome leads to mosaic focal ischemic neuronal injuries with maximum reduction in the level of catecholamines by 29.5±5.0% compared with control cases. Three–6 days after ICH on a background of selective neuronal necrosis in substantial number of neurons in the nuclei of the brainstem the level of catecholamines is significantly reduced. Conclusion. Disclosed observations reflect significant functional pathology of neurons responsible for the regulation of cardiorespiratory function and may underlie disturbances of integrative activity in the brain stem in general.

  1. A histopathological study of premature and mature infants with pontosubicular neuron necrosis: neuronal cell death in perinatal brain damage.

    Science.gov (United States)

    Takizawa, Yuji; Takashima, Sachio; Itoh, Masayuki

    2006-06-20

    Perinatal hypoxic-ischemic brain damage is a major cause of neuronal and behavior deficits, in which the onset of injury can be before, at or after birth, and the effects may be delayed. Pontosubicular neuron necrosis (PSN) is one of perinatal hypoxic-ischemic brain injury and its pathological peculiarity is neuronal apoptosis. In this study, we investigated whether apoptotic cascade of PSN used a caspase-pathway or not, and whether hypoglycemia activated apoptosis or not. Sections of the pons of PSN with and without hypoglycemia were stained using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and immunohistochemistry for glial fibrillary acidic protein (GFAP), Bcl-2, Bcl-x and activated caspase 3. Additionally, we performed immunoblot analysis of Bcl-2, Bcl-x and activated caspase 3. TUNEL-positive cell was closely associated with the presence of karyorrhexis. Under combination of karyorrhectic and TUNEL-positive cells, number of apoptotic cells in premature brains was significantly more than in mature brains. Hypoxic-ischemic brain injury was considered to easily lead to apoptosis in premature infants. Moreover, as this pathophysiology, caspase-pathway activation contributed to neuronal death from caspase-immunoexpression analyses. PSN with hypoglycemia showed large number of apoptotic cells and higher expression of activated caspase 3. The result may be more severe with the background of hypoglycemia and prematurity complicated by hypoxia and/or ischemia.

  2. Transplantation of bone marrow mesenchymal stem cells decreases oxidative stress, apoptosis, and hippocampal damage in brain of a spontaneous stroke model.

    Science.gov (United States)

    Calió, Michele Longoni; Marinho, Darci Sousa; Ko, Gui Mi; Ribeiro, Renata Rodrigues; Carbonel, Adriana Ferraz; Oyama, Lila Missae; Ormanji, Milene; Guirao, Tatiana Pinoti; Calió, Pedro Luiz; Reis, Luciana Aparecida; Simões, Manuel de Jesus; Lisbôa-Nascimento, Telma; Ferreira, Alice Teixeira; Bertoncini, Clélia Rejane Antônio

    2014-05-01

    Stroke is the most common cause of motor disabilities and is a major cause of mortality worldwide. Adult stem cells have been shown to be effective against neuronal degeneration through mechanisms that include both the recovery of neurotransmitter activity and a decrease in apoptosis and oxidative stress. We chose the lineage stroke-prone spontaneously hypertensive rat (SHRSP) as a model for stem cell therapy. SHRSP rats can develop such severe hypertension that they generally suffer a stroke at approximately 1 year of age. The aim of this study was to evaluate whether mesenchymal stem cells (MSCs) decrease apoptotic death and oxidative stress in existing SHRSP brain tissue. The results of qRT-PCR assays showed higher levels of the antiapoptotic Bcl-2 gene in the MSC-treated animals, compared with untreated. Our study also showed that superoxide, apoptotic cells, and by-products of lipid peroxidation decreased in MSC-treated SHRSP to levels similar those found in the animal controls, Wistar Kyoto rats. In addition, we saw a repair of morphological damage at the hippocampal region after MSC transplantation. These data suggest that MSCs have neuroprotective and antioxidant potential in stroke-prone spontaneously hypertensive rats.

  3. Comparison of cerebral blood flow pattern by transcranial Doppler in patients with diffuse and focal causes of brain death

    Directory of Open Access Journals (Sweden)

    Alireza Vakilian

    2012-01-01

    Full Text Available Background: This study aims to assess the cerebral vessels flow in brain death patients with different causes, including focal and diffuse lesions and comparison of flows according to the underlying causes. Materials and Methods: Two groups of 15 brain-dead patients one with focal and the other with diffuse brain lesions were compared according to their cerebral blood flow pattern 48 h passed brain death certification. Results: Bilateral absence of flow in middle cerebral artery (MCA was found in 54.5% of brain-dead patients with diffuse lesion and 50.33% of those with focal lesions. Systolic spike pattern in MCA flow was found in 46.2% of patients with focal lesion and 16.65% of patients with diffuse lesion. Diastole-systole separation pattern in MCA was seen in 16.65% of patients with the diffuse lesions. This pattern in MCA was not seen in patients with the focal lesion group. In carotid arteries, we did not find the absence of flow in any cases. Thirty percent of all patients in both groups had a normal flow pattern (36.6% of patients with focal lesions and 23.3% of patients with diffuse lesion. Patients with focal lesion had 33.3% systolic spike pattern flow and had 23.35% diastole-systole separation flow pattern. In intra-cranial vessels, systolic spike pattern was more common among patients with focal lesions than patients with diffuse lesion, however, this difference was not statistically significant (46.2% of patients with focal lesion and 16.65% of patients with diffuse lesion (P value = 0.244-0.09. Diastole-systole separation flow was more common in patients with diffuse lesions than those with the focal lesions although this could not reach the significant level as the previous pattern (20% of patients with diffuse lesion versus no case in patients with focal lesion (P value = 0.181. Conclusion: Absence of flow was the most common brain flow pattern in the focal and diffuse group lesions. There was no difference in flow pattern

  4. Guidelines for the pathoanatomical examination of the lower brain stem in ingestive and swallowing disorders and its application to a dysphagic spinocerebellar ataxia type 3 patient

    NARCIS (Netherlands)

    Rub, U; Brunt, ER; Del Turco, D; de Vos, RAI; Gierga, K; Paulson, H; Braak, H

    2003-01-01

    Despite the fact that considerable progress has been made in the last 20 years regarding the three-phase process of ingestion and the lower brain stem nuclei involved in it, no comprehensive descriptions of the ingestion-related lower brain stem nuclei are available for neuropathologists confronted

  5. MicroRNA network changes in the brain stem underlie the development of hypertension.

    Science.gov (United States)

    DeCicco, Danielle; Zhu, Haisun; Brureau, Anthony; Schwaber, James S; Vadigepalli, Rajanikanth

    2015-09-01

    Hypertension is a major chronic disease whose molecular mechanisms remain poorly understood. We compared neuroanatomical patterns of microRNAs in the brain stem of the spontaneous hypertensive rat (SHR) to the Wistar Kyoto rat (WKY, control). We quantified 419 well-annotated microRNAs in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM), from SHR and WKY rats, during three main stages of hypertension development. Changes in microRNA expression were stage- and region-dependent, with a majority of SHR vs. WKY differential expression occurring at the hypertension onset stage in NTS versus at the prehypertension stage in RVLM. Our analysis identified 24 microRNAs showing time-dependent differential expression in SHR compared with WKY in at least one brain region. We predicted potential gene regulatory targets corresponding to catecholaminergic processes, neuroinflammation, and neuromodulation using the miRWALK and RNA22 databases, and we tested those bioinformatics predictions using high-throughput quantitative PCR to evaluate correlations of differential expression between the microRNAs and their predicted gene targets. We found a novel regulatory network motif consisting of microRNAs likely downregulating a negative regulator of prohypertensive processes such as angiotensin II signaling and leukotriene-based inflammation. Our results provide new evidence on the dynamics of microRNA expression in the development of hypertension and predictions of microRNA-mediated regulatory networks playing a region-dependent role in potentially altering brain-stem cardiovascular control circuit function leading to the development of hypertension.

  6. B-Amyloid Precursor Protein Staining of the Brain in Sudden Infant and Early Childhood Death

    DEFF Research Database (Denmark)

    Jensen, Lisbeth Lund; Banner, Jytte; Ulhøi, Benedicte Parm

    2013-01-01

    To develop and validate a scoring method for assessing β-amyloid precursor protein (APP) staining in cerebral white matter and to investigate the occurrence, amount and deposition pattern based on the cause of death in infants and young children.......To develop and validate a scoring method for assessing β-amyloid precursor protein (APP) staining in cerebral white matter and to investigate the occurrence, amount and deposition pattern based on the cause of death in infants and young children....

  7. The gradual onset brain death model : a relevant model to study organ donation and its consequences on the outcome after transplantation

    NARCIS (Netherlands)

    Kolkert, Joe L. P.; van Dijk, Antony; Ottens, Petra J.; Ploeg, Rutger J.; Leuvenink, Henri G. D.; 't Hart, Nils

    2007-01-01

    Organs used for transplantation are usually derived from heart-beating brain dead donors. However, brain death is known to have negative effects on donor organ quality, previously studied using a difficult to control sudden onset experimental model. We have now developed a reproducible gradual onset

  8. Physical weight loading induces expression of tryptophan hydroxylase 2 in the brain stem.

    Directory of Open Access Journals (Sweden)

    Joon W Shim

    Full Text Available Sustaining brain serotonin is essential in mental health. Physical activities can attenuate mental problems by enhancing serotonin signaling. However, such activity is not always possible in disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects of voluntary exercise. Focusing on serotonergic signaling, we addressed a question: Does local mechanical loading to the skeleton elevate expression of tryptophan hydroxylase 2 (tph2 that is a rate-limiting enzyme for brain serotonin? A 5 min knee loading was applied to mice using 1 N force at 5 Hz for 1,500 cycles. A 5-min treadmill running was used as an exercise (positive control, and a 90-min tail suspension was used as a stress (negative control. Expression of tph2 was determined 30 min - 2 h in three brain regions --frontal cortex (FC, ventromedial hypothalamus (VMH, and brain stem (BS. We demonstrated for the first time that knee loading and treadmill exercise upregulated the mRNA level of tph2 in the BS, while tail suspension downregulated it. The protein level of tph2 in the BS was also upregulated by knee loading and downregulated by tail suspension. Furthermore, the downregulation of tph2 mRNA by tail suspension can be partially suppressed by pre-application of knee loading. The expression of tph2 in the FC and VMH was not significantly altered with knee loading. In this study we provided evidence that peripheral mechanical loading can activate central tph2 expression, suggesting that physical cues may mediate tph2-cathalyzed serotonergic signaling in the brain.

  9. The role of cancer stem cells and miRNAs in defining the complexities of brain metastasis

    OpenAIRE

    2013-01-01

    Researchers and clinicians have been challenged with the development of therapies for the treatment of cancer patients whose tumors metastasized to the brain. Among the most lethal weapons known today, current management of brain metastases involves multiple therapeutic modalities that provide little, if any, for improving the quality of life and overall survival. Recently the role of cancer stem cells (CSCs) in the development of cancer has been studied extensively, and thus its role in the ...

  10. Heart murmur and N-terminal pro-brain natriuretic peptide as predictors of death in 2977 consecutive hospitalized patients

    DEFF Research Database (Denmark)

    Iversen, Kasper; Nielsen, O.W.; Kirk, V.

    2008-01-01

    Background: Little is known about the prognostic importance of murmur in unselected patients. It is difficult to distinguish between innocent and significant murmurs. N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and BNP have recently been shown to be useful in small series of patients......-pro-BNP, discovery of valvular heart disease by echocardiography yielded no additional prognostic information. Conclusions: Detection of a cardiac murmur during routine medical examination of hospitalized patients is associated with increased risk of death within a year. A blood test for NT-pro-BNP gives significant...

  11. Brazilian guidelines for the application of transcranial ultrasound as a diagnostic test for the confirmation of brain death

    Directory of Open Access Journals (Sweden)

    Marcos C. Lange

    2012-05-01

    Full Text Available Neurosonological studies, specifically transcranial Doppler (TCD and transcranial color-coded duplex (TCCD, have high level of specificity and sensitivity and they are used as complementary tests for the diagnosis of brain death (BD. A group of experts, from the Neurosonology Department of the Brazilian Academy of Neurology, created a task force to determine the criteria for the following aspects of diagnosing BD in Brazil: the reliability of TCD methodology; the reliability of TCCD methodology; neurosonology training and skills; the diagnosis of encephalic circulatory arrest; and exam documentation for BD. The results of this meeting are presented in the current paper.

  12. Analysis on the training effect of criteria and practical guidance for determination of brain death: evoked potentials

    Directory of Open Access Journals (Sweden)

    Yan ZHANG

    2015-12-01

    Full Text Available Objective To analyze the training results of short-latency somatosensory-evoked potential (SLSEP for brain death determination and to improve the training program. Methods A total of 101 trainees received theoretical training, simulation skills training, bedside skills training and test analysis for SLSEP in brain death determination. The composition of trainees was analyzed and the error rates of 6 knowledge points were calculated. Univariate and multivariate backward Logistic regression analyses were used to analyze the influence of factors including sex, age, specialty, professional category, professional qualification and hospital level, on the error rates. Results Among them, trainees of 30-49 years old occupied 76.24% (77/101, most of them were from third grade, grade A hospitals (98.02%, 99/101, and 78 trainees (77.23% were from Department of Neurology. There were 82 clinicians (81.19%, 31 (30.69% had senior certificate and 42 (41.58% had intermediate certificate. Total error rate of 6 knowledge points was 4.50% (91/2020. Of the 6 knowledge points, the error rate of pitfalls was the highest (9.41%, 19/202, followed by result determination (5.94% , 12/202, recording techniques (4.75% , 24/505, procedures (3.96%, 32/808, sequence of confirmatory tests (1.98%, 2/101 and environmental conditions (0.99%, 2/202. Univariate and multivariate Logistic regression analyses showed that age (OR = 1.566, 95% CI: 1.116-2.197; P = 0.009 and professional qualification (OR = 1.669, 95% CI: 1.163-2.397; P = 0.005 were independent risk factors associated with high error rates. Conclusions The differences between brain death determination and routine check of SLSEP should be paid more attention to improve the quality of determination for brain death by SLSEP.  DOI: 10.3969/j.issn.1672-6731.2015.12.007

  13. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  14. A matter of respect: a defense of the dead donor rule and of a "whole-brain" criterion for determination of death.

    Science.gov (United States)

    Khushf, George

    2010-06-01

    Many accounts of the historical development of neurological criteria for determination of death insufficiently distinguish between two strands of interpretation advanced by advocates of a "whole-brain" criterion. One strand focuses on the brain as the organ of integration. Another provides a far more complex and nuanced account, both of death and of a policy on the determination of death. Current criticisms of the whole-brain criterion are effective in refuting the first interpretation, but not the second, which is advanced in the 2008 President's Council report on the determination of death. In this essay, I seek to further develop this second strand of interpretation. I argue that policy on determination of death aligns moral, biological, and ontological death concepts. Morally, death marks the stage when respect is no longer owed. Biologically, death concerns integrated functioning of an organism as a whole. But the biological concepts are underdetermined. The moral concerns lead to selection of strong individuality concepts rather than weak ones. They also push criteria to the "far side" of the dying process. There is a countervailing consideration associated with optimizing the number of available organs, and this pushes to the "near side" of death. Policy is governed by a conviction that it is possible to align these moral and biological death concepts, but this conviction simply lays out an agenda. There is also a prescription-integral to the dead donor rule-that lexically prioritizes the deontic concerns and that seeks to balance the countervailing tendencies by using science-based refinements to make the line between life and death more precise. After showing how these concerns have been effectively aligned in the current policy, I present a modified variant of a "division" scenario and show how an "inverse decapitation problem" leads to a conclusive refutation of the nonbrain account of death.

  15. EphrinB3 blocks EphB3 dependence receptor functions to prevent cell death following traumatic brain injury.

    Science.gov (United States)

    Theus, M H; Ricard, J; Glass, S J; Travieso, L G; Liebl, D J

    2014-05-08

    Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, have a variety of roles in the developing and adult central nervous system that require direct cell-cell interactions; including regulating axon path finding, cell proliferation, migration and synaptic plasticity. Recently, we identified a novel pro-survival role for ephrins in the adult subventricular zone, where ephrinB3 blocks Eph-mediated cell death during adult neurogenesis. Here, we examined whether EphB3 mediates cell death in the adult forebrain following traumatic brain injury and whether ephrinB3 infusion could limit this effect. We show that EphB3 co-labels with microtubule-associated protein 2-positive neurons in the adult cortex and is closely associated with ephrinB3 ligand, which is reduced following controlled cortical impact (CCI) injury. In the complete absence of EphB3 (EphB3(-/-)), we observed reduced terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL), and functional improvements in motor deficits after CCI injury as compared with wild-type and ephrinB3(-/-) mice. We also demonstrated that EphB3 exhibits dependence receptor characteristics as it is cleaved by caspases and induces cell death, which is not observed in the presence of ephrinB3. Following trauma, infusion of pre-clustered ephrinB3-Fc molecules (eB3-Fc) into the contralateral ventricle reduced cortical infarct volume and TUNEL staining in the cortex, dentate gyrus and CA3 hippocampus of wild-type and ephrinB3(-/-) mice, but not EphB3(-/-) mice. Similarly, application of eB3-Fc improved motor functions after CCI injury. We conclude that EphB3 mediates cell death in the adult cortex through a novel dependence receptor-mediated cell death mechanism in the injured adult cortex and is attenuated following ephrinB3 stimulation.

  16. Effects of Choto-san and hooks and stems of Uncaria sinensis on antioxidant enzyme activities in the gerbil brain after transient forebrain ischemia.

    Science.gov (United States)

    Yokoyama, Koichi; Shimada, Yutaka; Hori, Etsuro; Nakagawa, Takako; Takagi, Shinobu; Sekiya, Nobuyasu; Kouta, Kazufumi; Nishijo, Hisao; Yokozawa, Takako; Terasawa, Katsutoshi

    2004-12-01

    Previously, we revealed that oral administrations of Choto-san, a Kampo formula, and the hooks and stems of Uncaria sinensis Haviland (Rubiaceae), a medicinal plant comprising Choto-san, enhanced superoxide anion and hydroxyl radical scavenging activities in the hippocampus, and prevented delayed neuronal death of pyramidal cells in the hippocampal CA1 region in a transient forebrain ischemia gerbil model. In the present study, for the purpose of clarifying whether the endogenous antioxidant enzymes contribute to these mechanisms, we investigated the effects of Choto-san extract (CSE) and Uncaria sinensis extract (USE) on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the brain by using the same experimental model. 1.0% CSE or 3.0% USE were dissolved in water and provided to gerbils ad libitum from 7 days prior to ischemia/reperfusion (i/rp). Seven days of continuous administrations of CSE or USE without i/rp procedure enhanced CAT activity but not SOD and GSH-Px activities in both the hippocampus and cortex. CSE elevated CAT activity in the hippocampus at 7 days and in the cortex at 3h after i/rp. USE raised CAT activity in both the hippocampus and cortex at 3 h and 7 days after i/rp. These results suggest that one of the mechanisms of the protective effects of CSE and USE against transient brain ischemia-induced neuronal damage may be their enhancing effect on CAT activity in the brain.

  17. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury:a biomechanical evaluation

    Institute of Scientific and Technical Information of China (English)

    Zhong-jun Zhang; Ya-jun Li; Xiao-guang Liu; Feng-xiao Huang; Tie-jun Liu; Dong-mei Jiang; Xue-man Lv; Min Luo

    2015-01-01

    Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, max-imum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neu-rotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These ifndings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, im-prove biomechanical properties, and contribute to the recovery after injury.

  18. Collateralization of the pathways descending from the cerebral cortex to brain stem and spinal cord in cat and monkey

    NARCIS (Netherlands)

    K. Keizer (Koos)

    1989-01-01

    textabstractThe present study deals with the collateralization of the descending pathways from the cerebral cortex to the brain stem and the spinal cord in cat and monkey. The distributions of the branching cortical neurons were studied using retrograde fluorescent tracers. In addition, a new retrog

  19. Cognitive improvement following transvenous adipose-derived mesenchymal stem cell transplantation in a rat model of traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dongfei Li; Chun Yang; Rongmei Qu; Huiying Yang; Meichun Yu; Hui Tao; Jingxing Dai; Lin Yuan

    2011-01-01

    The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein.Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.

  20. The organ preservation and enhancement of donation success ratio effect of extracorporeal membrane oxygenation in circulatory unstable brain death donor.

    Science.gov (United States)

    Fan, Xiaoli; Chen, Zhiquan; Nasralla, David; Zeng, Xianpeng; Yang, Jing; Ye, Shaojun; Zhang, Yi; Peng, Guizhu; Wang, Yanfeng; Ye, Qifa

    2016-10-01

    Between 2010 and 2013, we recorded 66 cases of failed organ donation after brain death (DBD) due to the excessive use of the vasoactive drugs resulting in impaired hepatic and/or renal function. To investigate the effect of extracorporeal membrane oxygenation (ECMO) in donor management, ECMO was used to provide support for DBD donors with circulatory and/or respiratory failure from 2013 to 2015. A retrospective cohort study between circulatory non-stable DBD with vasoactive drugs (DBD-drug) and circulatory non-stable DBD with ECMO (DBD-ECMO) was designed to compare the transplant outcomes. A total of 19 brain death donors were supported by ECMO. The incidence rate of post-transplant liver primary non-function (PNF) was 10% (two of 20) in DBD-drug group and zero in DBD-ECMO group. Kidney function indicators, including creatinine clearance and urine production, were significantly better in DBD-ECMO group, as well as the kidney delayed graft function (DGF) rate was found to be decreased by the use of ECMO in our study. Donation success rate increased steadily from 47.8% in 2011 to 84.6% in 2014 after the ECMO intervention. The use of ECMO in assisting circulatory and respiratory function of DBD can reduce liver and kidney injury from vasoactive drugs, thereby improving organ quality and reducing the organ discard rates.

  1. EAAC1 Gene Deletion Increases Neuronal Death and Blood Brain Barrier Disruption after Transient Cerebral Ischemia in Female Mice

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2014-10-01

    Full Text Available EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-mediated transport of cysteine into neurons contributes to neuronal antioxidant function by providing cysteine substrates for glutathione synthesis. Here we evaluated the effects of EAAC1 gene deletion on hippocampal blood vessel disorganization after transient cerebral ischemia. EAAC1−/− female mice subjected to transient cerebral ischemia by common carotid artery occlusion for 30 min exhibited twice as much hippocampal neuronal death compared to wild-type female mice as well as increased reduction of neuronal glutathione, blood–brain barrier (BBB disruption and vessel disorganization. Pre-treatment of N-acetyl cysteine, a membrane-permeant cysteine prodrug, increased basal glutathione levels in the EAAC1−/− female mice and reduced ischemic neuronal death, BBB disruption and vessel disorganization. These findings suggest that cysteine uptake by EAAC1 is important for neuronal antioxidant function under ischemic conditions.

  2. Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

    Science.gov (United States)

    Quinn, K. J.; Didier, A. J.; Baker, J. F.; Peterson, B. W.

    1998-01-01

    A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

  3. Control of Outer Radial Glial Stem Cell Mitosis in the Human Brain

    Directory of Open Access Journals (Sweden)

    Bridget E.L. Ostrem

    2014-08-01

    Full Text Available Evolutionary expansion of the human neocortex is partially attributed to a relative abundance of neural stem cells in the fetal brain called outer radial glia (oRG. oRG cells display a characteristic division mode, mitotic somal translocation (MST, in which the soma rapidly translocates toward the cortical plate immediately prior to cytokinesis. MST may be essential for progenitor zone expansion, but the mechanism of MST is unknown, hindering exploration of its function in development and disease. Here, we show that MST requires activation of the Rho effector ROCK and nonmuscle myosin II, but not intact microtubules, centrosomal translocation into the leading process, or calcium influx. MST is independent of mitosis and distinct from interkinetic nuclear migration and saltatory migration. Our findings suggest that disrupted MST may underlie neurodevelopmental diseases affecting the Rho-ROCK-myosin pathway and provide a foundation for future exploration of the role of MST in neocortical development, evolution, and disease.

  4. [Diagnostic significance of the spinal-brain stem polysynaptic reflex and the period of inhibition].

    Science.gov (United States)

    Ivanichev, G A

    1985-01-01

    Electrical stimulation of the radial nerve associated with voluntary contraction of the shoulder girdle inhibited bioelectrical activity not only in the muscles of the hypothenar but also in the proximal muscles. In resting muscles, such stimulation elicited a reflex response with a large latent period. With weak voluntary tension stimulation elicited a reflex response while in the presence of considerable contraction the reflex response merged with bioelectrical activity, with a clearly demonstrable subsequent period of inhibition. The current viewpoint about the antidromal blockade of the segmental motoneurons is debated. It is suggested that the polysynaptic reflex and the inhibition period are connected with the same level of realization -- the oral portions of the brain stem.

  5. Fatal outcome after brain stem infarction related to bilateral vertebral artery occlusion - case report of a detrimental complication of cervical spine trauma

    Directory of Open Access Journals (Sweden)

    Beauchamp Kathryn M

    2011-07-01

    Full Text Available Abstract Background Vertebral artery injury (VAI after blunt cervical trauma occurs more frequently than historically believed. The symptoms due to vertebral artery (VA occlusion usually manifest within the first 24 hours after trauma. Misdiagnosed VAI or delay in diagnosis has been reported to cause acute deterioration of previously conscious and neurologically intact patients. Case presentation A 67 year-old male was involved in a motor vehicle crash (MVC sustaining multiple injuries. Initial evaluation by the emergency medical response team revealed that he was alert, oriented, and neurologically intact. He was transferred to the local hospital where cervical spine computed tomography (CT revealed several abnormalities. Distraction and subluxation was present at C5-C6 and a comminuted fracture of the left lateral mass of C6 with violation of the transverse foramen was noted. Unavailability of a spine specialist prompted the patient's transfer to an area medical center equipped with spine care capabilities. After arrival, the patient became unresponsive and neurological deficits were noted. His continued deterioration prompted yet another transfer to our Level 1 regional trauma center. A repeat cervical spine CT at our institution revealed significantly worsened subluxation at C5-C6. CT angiogram also revealed complete occlusion of bilateral VA. The following day, a repeat CT of the head revealed brain stem infarction due to bilateral VA occlusion. Shortly following, the patient was diagnosed with brain death and care was withdrawn. Conclusion Brain stem infarction secondary to bilateral VA occlusion following cervical spine trauma resulted in fatal outcome. Prompt imaging evaluation is necessary to assess for VAI in cervical trauma cases with facet joint subluxation/dislocation or transverse foramen fracture so that treatment is not delayed. Additionally, multiple transportation events are risk factors for worsening when unstable cervical

  6. Imminent brain death: point of departure for potential heart-beating organ donor recognition.

    NARCIS (Netherlands)

    Groot, Y.J. de; Jansen, N.E.; Bakker, J.; Kuiper, M.A.; Aerdts, S.; Maas, A.I.; Wijdicks, E.F.; Leiden, H.A. van; Hoitsma, A.J.; Kremer, H.P.H.; Kompanje, E.J.

    2010-01-01

    PURPOSE: There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for cr

  7. Imminent brain death: Point of departure for potential heart-beating organ donor recognition

    NARCIS (Netherlands)

    Y.J. de Groot (Yorick); N.E. Jansen (Nichon); J. Bakker (Jan); M.A. Kuiper (Michael); S. Aerdts (Stan); A.I.R. Maas (Andrew); E.F.M. Wijdicks (Eelco); H.A. van Leiden (Hendrik); A.J. Hoitsma (Andries); H.P.H. Kremer (Berry); E.J.O. Kompanje (Erwin)

    2010-01-01

    textabstractPurpose: There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We sea

  8. Imminent brain death : point of departure for potential heart-beating organ donor recognition

    NARCIS (Netherlands)

    de Groot, Yorick J.; Jansen, Nichon E.; Bakker, Jan; Kuiper, Michael A.; Aerdts, Stan; Maas, Andrew I. R.; Wijdicks, Eelco F. M.; van Leiden, Hendrik A.; Hoitsma, Andries J.; Kremer, Berry H. P. H.; Kompanje, Erwin J. O.

    2010-01-01

    There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria fo

  9. Analysis on the training effect of criteria and practical guidance for determination of brain death: transcranial Doppler

    Directory of Open Access Journals (Sweden)

    Lin-lin FAN

    2015-12-01

    Full Text Available Objective To analyze the training effects of transcranial Doppler (TCD for brain death determination conducted by Brain Injury Evaluation Quality Control Centre of National Health and Family Planning Commission to optimize the training program and improve the training effects. Methods A total of 106 trainees received theoretical training, simulation skill training, bedside skill training and test analysis on TCD confirmatory test for brain death determination. The composition of trainees was analyzed and the error rates of 6 knowledge points were calculated. Univariate and multivariate backward Logistic regression analyses were used to analyze the influence of factors including sex, age, specialty, professional category professional qualification and hospital level on the error rates. Results The trainees including 42 males and 64 females, came from 69 hospitals. Trainees of 30-49 years old occupied 77.36% (82/106. In the trainees, 96.23% (102/106 were from third grade, grade A hospitals, and most of them were from Department of Neurology (64.15% , 68/106 and Ultrasound (19.81% , 21/106. There were 82 clinicians (77.36%. Thirty four (32.08% trainees had senior certificate and 49 (46.23% had intermediate certificate. Total error rate of 6 knowledge points was 7.26% (149/2052. Of the 6 knowledge points, the error rate of parameter setting was the highest (9.43%, 10/106, followed by checking position (8.73%, 37/424, artery recognition (8.67%, 43/496, result determination (7.41%, 55/742, equipment (1.89%, 2/106 and pitfalls (1.12%, 2/178. Univariate and multivariate Logistic regression analyses showed that specialty (OR = 1.313, 95% CI: 1.072-1.610; P = 0.009 and hospital level (OR = 2.943, 95% CI: 1.623-5.338; P = 0.000 were independent risk factors associated with high error rates. Conclusions Among the trainees, degree of mastering the knowledge points is different, and the characteristics of trainees influence the training effect. The training

  10. Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis

    DEFF Research Database (Denmark)

    Larsen, TB; Nørgaard-Pedersen, B; Lundemose, JB

    2000-01-01

    . The vulnerability of the infant brain stem to ischemia has been suggested to be a conceivable cause of sudden infant death syndrome. This is compatible with a hypothesis that genetic risk factors for cerebral thrombosis could cause microinfarction in the brain stem during the first month of life, affecting vital......Sudden infant death syndrome or "cot death" has until the late eighties been a significant cause of death in children between the ages of 1 month and 1 year. Approximately two per 1000 children born alive dies of sudden infant death syndrome each year in Western Europe, North America, and Australia...... in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome...

  11. Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis

    DEFF Research Database (Denmark)

    Larsen, T B; Nørgaard-Pedersen, B; Banner, Jytte

    2000-01-01

    in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome......Sudden infant death syndrome or "cot death" has until the late eighties been a significant cause of death in children between the ages of 1 month and 1 year. Approximately two per 1000 children born alive dies of sudden infant death syndrome each year in Western Europe, North America, and Australia....... The vulnerability of the infant brain stem to ischemia has been suggested to be a conceivable cause of sudden infant death syndrome. This is compatible with a hypothesis that genetic risk factors for cerebral thrombosis could cause microinfarction in the brain stem during the first month of life, affecting vital...

  12. Decreased cysteine uptake by EAAC1 gene deletion exacerbates neuronal oxidative stress and neuronal death after traumatic brain injury.

    Science.gov (United States)

    Choi, Bo Young; Kim, In Yeol; Kim, Jin Hee; Lee, Bo Eun; Lee, Song Hee; Kho, A Ra; Jung, Hee Jae; Sohn, Min; Song, Hong Ki; Suh, Sang Won

    2016-07-01

    Excitatory amino acid carrier type 1 (EAAC1), a high-affinity glutamate transporter, can expend energy to move glutamate into neurons. However, under normal physiological conditions, EAAC1 does not have a great effect on glutamate clearance but rather participates in the neuronal uptake of cysteine. This process is critical to maintaining neuronal antioxidant function by providing cysteine for glutathione synthesis. Previous study showed that mice lacking EAAC1 show increased neuronal oxidative stress following transient cerebral ischemia. In the present study, we sought to characterize the role of EAAC1 in neuronal resistance after traumatic brain injury (TBI). Young adult C57BL/6 wild-type or EAAC1 (-/-) mice were subjected to a controlled cortical impact model for TBI. Neuronal death after TBI showed more than double the number of degenerating neurons in the hippocampus in EAAC1 (-/-) mice compared with wild-type mice. Superoxide production, zinc translocation and microglia activation similarly showed a marked increase in the EAAC1 (-/-) mice. Pretreatment with N-acetyl cysteine (NAC) reduced TBI-induced neuronal death, superoxide production and zinc translocation. These findings indicate that cysteine uptake by EAAC1 is important for neuronal antioxidant function and survival following TBI. This study also suggests that administration of NAC has therapeutic potential in preventing TBI-induced neuronal death.

  13. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

    Directory of Open Access Journals (Sweden)

    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  14. Dialysis Disequilibrium Syndrome: Brain death following hemodialysis for metabolic acidosis and acute renal failure – A case report

    Directory of Open Access Journals (Sweden)

    Bagshaw Sean M

    2004-08-01

    Full Text Available Abstract Background Dialysis disequilibrium syndrome (DDS is the clinical phenomenon of acute neurologic symptoms attributed to cerebral edema that occurs during or following intermittent hemodialysis (HD. We describe a case of DDS-induced cerebral edema that resulted in irreversible brain injury and death following acute HD and review the relevant literature of the association of DDS and HD. Case Presentation A 22-year-old male with obstructive uropathy presented to hospital with severe sepsis syndrome secondary to pneumonia. Laboratory investigations included a pH of 6.95, PaCO2 10 mmHg, HCO3 2 mmol/L, serum sodium 132 mmol/L, serum osmolality 330 mosmol/kg, and urea 130 mg/dL (46.7 mmol/L. Diagnostic imaging demonstrated multifocal pneumonia, bilateral hydronephrosis and bladder wall thickening. During HD the patient became progressively obtunded. Repeat laboratory investigations showed pH 7.36, HCO3 19 mmol/L, potassium 1.8 mmol/L, and urea 38.4 mg/dL (13.7 mmol/L (urea-reduction-ratio 71%. Following HD, spontaneous movements were absent with no pupillary or brainstem reflexes. Head CT-scan showed diffuse cerebral edema with effacement of basal cisterns and generalized loss of gray-white differentiation. Brain death was declared. Conclusions Death is a rare consequence of DDS in adults following HD. Several features may have predisposed this patient to DDS including: central nervous system adaptations from chronic kidney disease with efficient serum urea removal and correction of serum hyperosmolality; severe cerebral intracellular acidosis; relative hypercapnea; and post-HD hemodynamic instability with compounded cerebral ischemia.

  15. Progesterone promotes neuronal differentiation of human umbilical cord mesenchymal stem cells in culture conditions that mimic the brain microenvironment

    Institute of Scientific and Technical Information of China (English)

    Xianying Wang; Honghai Wu; Gai Xue; Yanning Hou

    2012-01-01

    In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vaginal delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the brain microenvironment). Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone (0.1, 1, 10 μM) in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 μM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment.

  16. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

    Directory of Open Access Journals (Sweden)

    Alvarim LT

    2014-08-01

    Full Text Available Larissa T Alvarim,1,3,* Leopoldo P Nucci,2,* Javier B Mamani,1 Luciana C Marti,1 Marina F Aguiar,1,2 Helio R Silva,1,3 Gisele S Silva,1 Mariana P Nucci-da-Silva,4 Elaine A DelBel,5,6 Lionel F Gamarra1–31Hospital Israelita Albert Einstein, São Paulo, Brazil; 2Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil; 3Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil; 4Departamento de Radiologia, Hospital das Clínicas, Universidade de São Paulo, Brazil; 5Universidade de São Paulo-Faculdade de Odontologia de Ribeirão Preto, São Paulo, Brazil; 6NAPNA- Núcleo de Apoio a Pesquisa em Neurociências Aplicadas, São Paulo, Brazil*These authors contributed equally to this workAbstract: The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson’s disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.Keywords: iron oxide, dementia, stem cell, stroke, Parkinson’s disease, sclerosis disease, brain aging

  17. Inflammatory responses are not sufficient to cause delayed neuronal death in ATP-induced acute brain injury.

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    Hey-Kyeong Jeong

    Full Text Available BACKGROUND: Brain inflammation is accompanied by brain injury. However, it is controversial whether inflammatory responses are harmful or beneficial to neurons. Because many studies have been performed using cultured microglia and neurons, it has not been possible to assess the influence of multiple cell types and diverse factors that dynamically and continuously change in vivo. Furthermore, behavior of microglia and other inflammatory cells could have been overlooked since most studies have focused on neuronal death. Therefore, it is essential to analyze the precise roles of microglia and brain inflammation in the injured brain, and determine their contribution to neuronal damage in vivo from the onset of injury. METHODS AND FINDINGS: Acute neuronal damage was induced by stereotaxic injection of ATP into the substantia nigra pars compacta (SNpc and the cortex of the rat brain. Inflammatory responses and their effects on neuronal damage were investigated by immunohistochemistry, electron microscopy, quantitative RT-PCR, and stereological counting, etc. ATP acutely caused death of microglia as well as neurons in a similar area within 3 h. We defined as the core region the area where both TH(+ and Iba-1(+ cells acutely died, and as the penumbra the area surrounding the core where Iba-1(+ cells showed activated morphology. In the penumbra region, morphologically activated microglia arranged around the injury sites. Monocytes filled the damaged core after neurons and microglia died. Interestingly, neither activated microglia nor monocytes expressed iNOS, a major neurotoxic inflammatory mediator. Monocytes rather expressed CD68, a marker of phagocytic activity. Importantly, the total number of dopaminergic neurons in the SNpc at 3 h (∼80% of that in the contralateral side did not decrease further at 7 d. Similarly, in the cortex, ATP-induced neuron-damage area detected at 3 h did not increase for up to 7 d. CONCLUSIONS: Different cellular

  18. Muerte cerebral en una embarazada y sobrevida del feto Brain death in a pregnant woman and fetus survival

    Directory of Open Access Journals (Sweden)

    Raúl Mejía

    2008-12-01

    Full Text Available Se presenta el caso de una mujer de 29 años de edad que a consecuencia de una hemorragia cerebelosa presentó un cuadro de muerte cerebral mientras cursaba la 17 semana de su embarazo. Durante 56 días se mantuvo con sostén vital artificial, corrección de déficit hormonal, nutrición enteral y tratamiento de las infecciones. Durante la 25 semana de embarazo, por paro cardíaco se debió practicar una cesárea, naciendo un niño de 450 gramos. Se realizó una revisión de los casos similares publicados y se discuten algunos aspectos médicos, éticos y legales derivados de esta situación.A 29 year old woman suffered massive brain injury after a cerebellum hemorrhage at 17 weeks' gestation. Several hours later, and after brainstem test, she was declared brain dead. She was supported with intensive care during 56 days. After a cardiac arrest, on week 25, a 450 g infant was delivered through a cesarean section. The somatic support of mother and fetus according to the expected physiologic changes after brain death and its ethical implications are discussed.

  19. Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons.

    Science.gov (United States)

    Brown, Maile R; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H; Kaczmarek, Leonard K

    2016-07-01

    Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express "high threshold" voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders.

  20. A Case of Primary Central Nervous System Lymphoma Located at Brain Stem in a Child

    Science.gov (United States)

    Kim, Jinho

    2016-01-01

    Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis. PMID:27867930

  1. The attitudes of brain cancer patients and their caregivers towards death and dying: a qualitative study

    Directory of Open Access Journals (Sweden)

    Kimmelman Jonathan

    2007-11-01

    Full Text Available Abstract Background Much money and energy has been spent on the study of the molecular biology of malignant brain tumours. However, little attention has been paid to the wishes of patients afflicted with these incurable tumours, and how this might influence treatment considerations. Methods We interviewed 29 individuals – 7 patients dying of a malignant brain tumor and 22 loved ones. One-on-one interviews were conducted according to a pre-designed interview guide. A combination of open-ended questions, as well as clinical scenarios was presented to participants in order to understand what is meaningful and valuable to them when determining treatment options and management approaches. The results were analyzed, coded, and interpreted using qualitative analytic techniques in order to arrive at several common overarching themes. Results Seven major themes were identified. In general, respondents were united in viewing brain cancer as unique amongst malignancies, due in large part to the premium placed on mental competence and cognitive functioning. Importantly, participants found their experiences, however difficult, led to the discovery of inner strength and resilience. Responses were usually framed within an interpersonal context, and participants were generally grateful for the opportunity to speak about their experiences. Attitudes towards religion, spirituality, and euthanasia were also probed. Conclusion Several important themes underlie the experiences of brain cancer patients and their caregivers. It is important to consider these when managing these patients and to respect not only their autonomy but also the complex interpersonal toll that a malignant diagnosis can have.

  2. Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

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    Olga M. Pulido

    2008-02-01

    Full Text Available Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors eliciting a very rapid and potent neurotoxic response. The hippocampus, among other brain regions, has been identified as a specific target site having high sensitivity to DOM toxicity. Histopathology evidence indicates that in addition to neurons, the astrocytes were also injured. Electron microscopy data reported in this study further supports the light microscopy findings. Furthermore, the effect of DOM was confirmed by culturing primary astrocytes from the hippocampus and the brain stem and subsequently exposing them to domoic acid. The RNA was extracted and used for biomarker analysis. The biomarker analysis was done for the early response genes including c-fos, c-jun, c-myc, Hsp-72; specific marker for the astrocytes- GFAP and the glutamate receptors including GluR 2, NMDAR 1, NMDAR 2A and B. Although, the astrocyte-GFAP and c-fos were not affected, c-jun and GluR 2 were down-regulated. The microarray analysis revealed that the chemokines / cytokines, tyrosine kinases (Trk, and apoptotic genes were altered. The chemokines that were up-regulated included - IL1-a, IL-1B, IL-6, the small inducible cytokine, interferon protein IP-10, CXC chemokine LIX, and IGF binding proteins. The Bax, Bcl-2, Trk A and Trk B were all downregulated. Interestingly, only the hippocampal astrocytes were affected. Our findings suggest that astrocytes may present a possible target for pharmacological interventions for the prevention and treatment of amnesic shellfish poisoning and for other brain pathologies involving excitotoxicity

  3. Analysis on the training effect of criteria and practical guidance for determination of brain death: clinical diagnosis

    Directory of Open Access Journals (Sweden)

    Ying-ying SU

    2015-12-01

    Full Text Available Objective Clinical diagnosis is the most predominant in the criteria for determination of brain death. This paper aims to analyze the training results of clinical diagnosis for brain death determination and to improve the training program. Methods A total of 461 trainees received theoretical training, simulation skills training, bedside skills training and test analysis. The composition of trainees was analyzed and the error rates of knowledge points were calculated. Univariate and multivariate backward Logistic regression analyses were used to analyze the influence of factors including sex, age, specialty, professional qualification and hospital level, on the error rates. Results Four hundred and sixty-one trainees came from 161 hospitals. Among them, trainees of 30-49 years old occupied 77.87% (359/461, and most of them came from third grade, grade A hospitals (88.29%, 407/461. There were 200 trainees (43.39% from Department of Neurology, 109 trainees (23.64% from Department of Neurosurgery, and 88 trainees (19.09% from Intensive Care Unit. Most of them (66.59%, 307/461 had senior certificate. Total error rate of 13 knowledge points was 5.81% (1054/18 128. The error rate of corneal reflex was the highest (24.64% , 104/422, followed by deep coma (11.59% , 365/3149, oculocephalogyric reflex (9.48%, 40/422, step and time of determination (7.48%, 138/1844, and pupillary light reflex (5.10% , 90/1766. Univariate and multivariate Logistic regression analyses showed that age (OR = 1.558, 95%CI: 1.435-1.693; P = 0.000, specialty (OR = 1.080, 95%CI: 1.021-1.143; P = 0.007 and hospital level (OR = 1.395, 95%CI: 1.174-1.659; P = 0.000 were independent risk factors associated with high error rates. Conclusions The training patterns and methods of clinical diagnosis for brain death determination should be further improved, especially the individual training, to rise the training quality. DOI: 10.3969/j.issn.1672-6731.2015.12.006

  4. Recent advances in the involvement of long non-coding RNAs in neural stem cell biology and brain pathophysiology

    Directory of Open Access Journals (Sweden)

    Daphne eAntoniou

    2014-04-01

    Full Text Available Exploration of non-coding genome has recently uncovered a growing list of formerly unknown regulatory long non-coding RNAs (lncRNAs with important functions in stem cell pluripotency, development and homeostasis of several tissues. Although thousands of lncRNAs are expressed in mammalian brain in a highly patterned manner, their roles in brain development have just begun to emerge. Recent data suggest key roles for these molecules in gene regulatory networks controlling neuronal and glial cell differentiation. Analysis of the genomic distribution of genes encoding for lncRNAs indicates a physical association of these regulatory RNAs with transcription factors (TFs with well-established roles in neural differentiation, suggesting that lncRNAs and TFs may form coherent regulatory networks with important functions in neural stem cells (NSCs. Additionally, many studies show that lncRNAs are involved in the pathophysiology of brain-related diseases/disorders. Here we discuss these observations and investigate the links between lncRNAs, brain development and brain-related diseases. Understanding the functions of lncRNAs in NSCs and brain organogenesis could revolutionize the basic principles of developmental biology and neuroscience.

  5. Adenovirus-mediated human brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem cell transplantation for spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Changsheng Wang; Jianhua Lin; Chaoyang Wu; Rongsheng Chen

    2011-01-01

    Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1, 3, and 5 weeks after transplantation, the expression of ??brain-derived neurotrophic factor and neurofilament-200 was upregulated in the injured spinal cord, spinal cord injury was alleviated, and Basso-Beattie-Bresnahan scores of hindlimb motor function were significantly increased. This evidence suggested that intravenous transplantation of adenovirus- mediated brain-derived neurotrophic factor gene-modified rat bone marrow mesenchymal stem cells could play a dual role, simultaneously providing neural stem cells and neurotrophic factors.

  6. Caffeic acid phenethyl ester prevents apoptotic cell death in the developing rat brain after pentylenetetrazole-induced status epilepticus.

    Science.gov (United States)

    Yiş, Uluç; Topçu, Yasemin; Özbal, Seda; Tuğyan, Kazım; Bayram, Erhan; Karakaya, Pakize; Yilmaz, Osman; Kurul, Semra Hız

    2013-11-01

    Population-based studies suggest that seizure incidence is highest during the first year of life, and early-life seizures frequently result in the development of epilepsy and behavioral alterations later in life. The early-life insults like status epilepticus often lead to epileptogenesis, a process in which initial brain injury triggers cascades of molecular, cellular, and network changes and eventually spontaneous seizures. Caffeic acid phenethyl ester is an active component of propolis obtained from honeybees and has neuroprotective properties. The aim of this study was to investigate whether caffeic acid phenethyl ester exerts neuroprotective effects on the developing rat brain after status epilepticus. Twenty-one dams reared Wistar male rats, and 21-day-old rats were divided into three groups: control group, pentylenetetrazole-induced status epilepticus group, and caffeic acid phenethyl ester-treated group. Status epilepticus was induced on the first day of experiment. Caffeic acid phenethyl ester injections (30 mg/kg intraperitoneally) started 40 min after the tonic phase of status epilepticus was reached, and the injections of caffeic acid phenethyl ester were repeated over 5 days. Rats were sacrificed, and brain tissues were collected on the 5th day of experiment after the last injection of caffeic acid phenethyl ester. Apoptotic cell death was evaluated. Histopathological examination showed that caffeic acid phenethyl ester significantly preserved the number of neurons in the CA1, CA3, and dentate gyrus regions of the hippocampus and the prefrontal cortex. It also diminished apoptosis in the hippocampus and the prefrontal cortex. In conclusion, this experimental study suggests that caffeic acid phenethyl ester administration may be neuroprotective in status epilepticus in the developing rat brain.

  7. Drosophila Brat and Human Ortholog TRIM3 Maintain Stem Cell Equilibrium and Suppress Brain Tumorigenesis by Attenuating Notch Nuclear Transport.

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    Mukherjee, Subhas; Tucker-Burden, Carol; Zhang, Changming; Moberg, Kenneth; Read, Renee; Hadjipanayis, Costas; Brat, Daniel J

    2016-04-15

    Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. Mutation of a single gene in Drosophila, Brain Tumor (Brat), leads to disrupted asymmetric cell division resulting in dramatic neoplastic proliferation of neuroblasts and massive larval brain overgrowth. To uncover the mechanisms relevant to deregulated cell division in human glioma stem cells, we first developed a novel adult Drosophila brain tumor model using brat-RNAi driven by the neuroblast-specific promoter inscuteable Suppressing Brat in this population led to the accumulation of actively proliferating neuroblasts and a lethal brain tumor phenotype. brat-RNAi caused upregulation of Notch signaling, a node critical for self-renewal, by increasing protein expression and enhancing nuclear transport of Notch intracellular domain (NICD). In human glioblastoma, we demonstrated that the human ortholog of Drosophila Brat, tripartite motif-containing protein 3 (TRIM3), similarly suppressed NOTCH1 signaling and markedly attenuated the stem cell component. We also found that TRIM3 suppressed nuclear transport of active NOTCH1 (NICD) in glioblastoma and demonstrated that these effects are mediated by direct binding of TRIM3 to the Importin complex. Together, our results support a novel role for Brat/TRIM3 in maintaining stem cell equilibrium and suppressing tumor growth by regulating NICD nuclear transport. Cancer Res; 76(8); 2443-52. ©2016 AACR.

  8. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

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    Zhu, Changlian [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Gao, Jianfeng [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Department of Physiology, Henan Traditional Medical University (China); Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Kuhn, Hans-Georg [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Blomgren, Klas, E-mail: klas.blomgren@neuro.gu.se [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatric Oncology, The Queen Silvia Children' s Hospital, Gothenburg (Sweden)

    2011-01-07

    Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  9. Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy

    Institute of Scientific and Technical Information of China (English)

    Min XU; Hui-ling ZHANG

    2011-01-01

    Autophagy is a highly regulated cellular mechanism that leads to degradation of long-lived proteins and dysfunctional organelles. The process has been implicated in a variety of physiological and pathological conditions relevant to neurological diseases. Recent studies show the existence of autophagy in cerebral ischemia, but no consensus has yet been reached regarding the functions of autophagy in this condition. This article highlights the activation of autophagy during cerebral ischemia and/or reperfusion, especially in neurons and astrocytes, as well as the role of autophagy in neuronal or astrocytic cell death and survival. We propose that physiological levels of autophagy, presumably caused by mild to modest hypoxia or ischemia, appear to be protective. However, high levels of autophagy caused by severe hypoxia or ischemia and/or reperfusion may cause self-digestion and eventual neuronal and astrocytic cell death. We also discuss that oxidative and endoplasmic reticulum (ER) stresses in cerebral hypoxia or ischemia and/or reperfusion are potent stimuli of autophagy in neurons and astrocytes. In addition, we review the evidence suggesting a considerable overlap between autophagy on one hand, and apoptosis, necrosis and necroptosis on the other hand, in determining the outcomes and final morphology of damaged neurons and astrocytes.

  10. Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain.

    Science.gov (United States)

    Duncan, Jeremy; Wang, Niping; Zhang, Xiao; Johnson, Shakevia; Harris, Sharonda; Zheng, Baoying; Zhang, Qinli; Rajkowska, Grazyna; Miguel-Hidalgo, Jose Javier; Sittman, Donald; Ou, Xiao-Ming; Stockmeier, Craig A; Wang, Jun Ming

    2015-07-01

    Major depressive disorder and alcoholism are significant health burdens that can affect executive functioning, cognitive ability, job responsibilities, and personal relationships. Studies in animal models related to depression or alcoholism reveal that the expression of Krüppel-like factor 11 (KLF11, also called TIEG2) is elevated in frontal cortex, which suggests that KLF11 may play a role in stress- or ethanol-induced psychiatric conditions. KLF11 is a transcriptional activator of monoamine oxidase A and B, but also serves other functions in cell cycle regulation and apoptotic cell death. In the present study, immunohistochemistry was used to quantify intensity of nuclear KLF11, combined with an unbiased stereological approach to assess nuclei in fronto-limbic, limbic, and other brain regions of rats exposed chronically to social defeat or ethanol. KLF11 immunoreactivity was increased significantly in the medial prefrontal cortex, frontal cortex, and hippocampus of both stressed rats and rats fed ethanol. However, expression of KLF11 protein was not significantly affected in the thalamus, hypothalamus, or amygdala in either treatment group compared to respective control rats. Triple-label immunofluorescence revealed that KLF11 protein was localized in nuclei of neurons and astrocytes. KLF11 was also co-localized with the immunoreactivity of cleaved caspase-3. In addition, Western blot analysis revealed a significant reduction in anti-apoptotic protein, Bcl-xL, but an increase of caspase-3 expression in the frontal cortex of ethanol-treated rats compared to ethanol-preferring controls. Thus, KLF11 protein is up-regulated following chronic exposure to stress or ethanol in a region-specific manner and may contribute to pro-apoptotic signaling in ethanol-treated rats. Further investigation into the KLF11 signaling cascade as a mechanism for neurotoxicity and cell death in depression and alcoholism may provide novel pharmacological targets to lessen brain damage and

  11. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    Science.gov (United States)

    Mouhieddine, Tarek H.; Nokkari, Amaly; Itani, Muhieddine M.; Chamaa, Farah; Bahmad, Hisham; Monzer, Alissar; El-Merahbi, Rabih; Daoud, Georges; Eid, Assaad; Kobeissy, Firas H.; Abou-Kheir, Wassim

    2015-01-01

    Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK) pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs) are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a) were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma) and SH-SY5Y (neuroblastoma) cell lines. Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU) of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence. PMID:26635517

  12. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tarek H. Mouhieddine

    2015-11-01

    Full Text Available Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma and SHSY-5Y (neuroblastoma cell lines.Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence.

  13. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.

    Science.gov (United States)

    Suzuki, Ikuo K; Vanderhaeghen, Pierre

    2015-09-15

    The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types. While the translational potential of PSC technologies for disease modeling and/or cell replacement therapies is usually put forward as a rationale for their utility, they are also opening novel windows for direct observation and experimentation of the basic mechanisms of human brain development. PSC-based studies have revealed that a number of cardinal features of neural ontogenesis are remarkably conserved in human models, which can be studied in a reductionist fashion. They have also revealed species-specific features, which constitute attractive lines of investigation to elucidate the mechanisms underlying the development of the human brain, and its link with evolution.

  14. Programmed Cell Death in the Honey Bee (Apis mellifera) (Hymenoptera: Apidae) Worker Brain Induced by Imidacloprid.

    Science.gov (United States)

    Wu, Yan-Yan; Zhou, Ting; Wang, Qiang; Dai, Ping-Li; Xu, Shu-Fa; Jia, Hui-Ru; Wang, Xing

    2015-08-01

    Honey bees are at an unavoidable risk of exposure to neonicotinoid pesticides, which are used worldwide. Compared with the well-studied roles of these pesticides in nontarget site (including midgut, ovary, or salivary glands), little has been reported in the target sites, the brain. In the current study, laboratory-reared adult worker honey bees (Apis mellifera L.) were treated with sublethal doses of imidacloprid. Neuronal apoptosis was detected using the TUNEL technique for DNA labeling. We observed significantly increased apoptotic markers in dose- and time-dependent manners in brains of bees exposed to imidacloprid. Neuronal activated caspase-3 and mRNA levels of caspase-1, as detected by immunofluorescence and real-time quantitative PCR, respectively, were significantly increased, suggesting that sublethal doses of imidacloprid may induce the caspase-dependent apoptotic pathway. Additionally, the overlap of apoptosis and autophagy in neurons was confirmed by transmission electron microscopy. It further suggests that a relationship exists between neurotoxicity and behavioral changes induced by sublethal doses of imidacloprid, and that there is a need to determine reasonable limits for imidacloprid application in the field to protect pollinators.

  15. Maternal brain death, pregnancy and the foetus: the medico-legal implications for Ireland.

    Science.gov (United States)

    Sheikh, Asim A; Cusack, Denis A

    2004-01-01

    This paper examines some of the medico-legal issues that arose as a result of a situation which occurred in May 2001 in Ireland when a woman who was a British citizen and who was fourteen weeks pregnant collapsed and suffered a brain haemorrhage. She was taken to hospital where she was placed on life support but declared brain-dead. As a result of the uncertainty regarding the hospital's obligation to the foetus, life-support was maintained until further opinion was sought. After two weeks the foetus died and life support was only then discontinued. In Ireland there currently exists neither medical guidelines nor legislation to regulate such areas of medical practice. Also, the courts have not had the opportunity to comment on this particular matter and thus there exists widespread concern as to how healthcare providers will act if such situation were to occur again in the future. This article examines the following difficult medico-legal implications that arise from the above situation and especially in light of the constitutional protection of the unborn child in Ireland.

  16. Radiation induces progenitor cell death, microglia activation, and blood-brain barrier damage in the juvenile rat cerebellum

    Science.gov (United States)

    Zhou, Kai; Boström, Martina; Ek, C. Joakim; Li, Tao; Xie, Cuicui; Xu, Yiran; Sun, Yanyan; Blomgren, Klas; Zhu, Changlian

    2017-01-01

    Posterior fossa tumors are the most common childhood intracranial tumors, and radiotherapy is one of the most effective treatments. However, irradiation induces long-term adverse effects that can have significant negative impacts on the patient’s quality of life. The purpose of this study was to characterize irradiation-induced cellular and molecular changes in the cerebellum. We found that irradiation-induced cell death occurred mainly in the external germinal layer (EGL) of the juvenile rat cerebellum. The number of proliferating cells in the EGL decreased, and 82.9% of them died within 24 h after irradiation. Furthermore, irradiation induced oxidative stress, microglia accumulation, and inflammation in the cerebellum. Interestingly, blood-brain barrier damage and blood flow reduction was considerably more pronounced in the cerebellum compared to other brain regions. The cerebellar volume decreased by 39% and the migration of proliferating cells to the internal granule layer decreased by 87.5% at 16 weeks after irradiation. In the light of recent studies demonstrating that the cerebellum is important not only for motor functions, but also for cognition, and since treatment of posterior fossa tumors in children typically results in debilitating cognitive deficits, this differential susceptibility of the cerebellum to irradiation should be taken into consideration for future protective strategies. PMID:28382975

  17. Identification and culture of neural stem cells isolated from adult rat subventricular zone following fluid percussion brain injury

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To analyze proliferation and differentiation of glial fibrillary acid protein(GFAP)-and nestin-positive(GFAP+/nestin+)cells isolated from the subventricular zone following fluid percussion brain injury to determine whether GFAP+/nestin+ cells exhibit characteristics of neural stem cells.Methods Male Sprague-Dawley rats,aged 12 weeks and weighing 200-250 g,were randomly and evenly assigned to normal control group and model group.In the model group,a rat model of fluid percussion brain injury was es...

  18. Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells

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    Kito, Hiroaki [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Yamazaki, Daiju [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Ohya, Susumu; Yamamura, Hisao [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)

    2011-07-29

    Highlights: {yields} We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. {yields} The ER stress facilitated the expression of inward rectifier K{sup +} channel (K{sub ir}2.1) and induced sustained membrane hyperpolarization. {yields} The membrane hyperpolarization induced sustained Ca{sup 2+} entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. {yields} The K{sub ir}2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K{sup +} channel (K{sub ir}2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K{sub ir} channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca{sup 2+} concentration due to Ca{sup 2+} influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K{sub ir}2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.

  19. Protective effect of bone marrow-derived mesenchymal stem cells on dopaminergic neurons against 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in rat brain slices

    Institute of Scientific and Technical Information of China (English)

    Lirong Jin; Zhen Hong; Chunjiu Zhong; Yang Wang

    2009-01-01

    BACKGROUND: To date, the use of bone marrow-derived mesenchymal stem cells (MSCs) for the treatment of Parkinson's disease have solely focused on in vivo animal models. Because of the number of influencing factors, it has been difficult to determine a consistent outcome. OBJECTIVE: To establish an injury model in brain slices of substantia nigra and striatum using 1-methyl-4-phenylpytidinium ion (MPP+), and to investigate the effect of MSCs on dopaminergic neurons following MPP+ induced damage.DESIGN, TIME AND SETTING: An in vitro, randomized, controlled, animal experiment using immunohistochemistry was performed at the Laboratory of the Department of Anatomy, Fudan University between January 2004 and December 2006.MATERIALS: Primary MSC cultures were obtained from femurs and tibias of adult Sprague Dawley rats. Organotypic brain slices were isolated from substantia nigra and striatum of 1-day-old Sprague Dawley rat pups. Monoclonal antibodies for tyrosine hydroxylase (TH, 1:5 000) were from Santa Cruz (USA); goat anti-rabbit IgG antibodies labeled with FITC were from Boster Company (China).METHODS: Organotypic brain slices were cultured for 5 days in whole culture medium supplemented with 50% DMEM, 25% equine serum, and 25% Tyrode's balanced salt solution. The medium was supplemented with 5 μg/mL Ara-C, and the culture was continued for an additional 5 days. The undergrowth of brain slices was discarded at day 10. Eugonic brain slices were cultured with basal media for an additional 7 days. The brain slices were divided into three groups: control, MPP+ exposure, and co-culture. For the MPP+ group, MPP+ (30 μmol/L) was added to the media at day 17 and brain slices were cultured for 4 days, followed by control media. For the co-culture group, the MPP+ injured brain slices were placed over MSCs in the well and were further cultured for 7 days.MAIN OUTCOME MEASURES: After 28 days in culture, neurite outgrowth was examined in the brain slices under phase

  20. The Brain Microenvironment Preferentially Enhances the Radioresistance of CD133+ Glioblastoma Stem-like Cells

    Directory of Open Access Journals (Sweden)

    Muhammad Jamal

    2012-02-01

    Full Text Available Brain tumor xenografts initiated from glioblastoma (GBM CD133+ tumor stem-like cells (TSCs are composed of TSC and non-TSC subpopulations, simulating the phenotypic heterogeneity of GBMs in situ. Given that the discrepancies between the radiosensitivity of GBM cells in vitro and the treatment response of patients suggest a role for the microenvironment in GBM radioresistance, we compared the response of TSCs and non-TSCs irradiated under in vitro and orthotopic conditions. As a measure of radioresponse determined at the individual cell level, γH2AX and 53BP1 foci were quantified in CD133+ cells and their differentiated (CD133- progeny. Under in vitro conditions, no difference was detected between CD133+ and CD133- cells in foci induction or dispersal after irradiation. However, irradiation of orthotopic xenografts initiated from TSCs resulted in the induction of fewer γH2AX and 53BP1 foci in CD133+ cells compared to their CD133- counterparts within the same tumor. Xenograft irradiation resulted in a tumor growth delay of approximately 7 days with a corresponding increase in the percentage of CD133+ cells at 7 days after radiation, which persisted to the onset of neurologic symptoms. These results suggest that, although the radioresponse of TSCs and non-TSCs does not differ under in vitro growth conditions, CD133+ cells are relatively radioresistant under intracerebral growth conditions. Whereas these findings are consistent with the suspected role for TSCs as a determinant of GBM radioresistance, these data also illustrate the dependence of the cellular radioresistance on the brain microenvironment.

  1. Presenilins are required for maintenance of neural stem cells in the developing brain

    Directory of Open Access Journals (Sweden)

    Kim Woo-Young

    2008-01-01

    Full Text Available Abstract The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11. In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, as evidenced by displacement of S-phase and M-phase nuclei in the ventricular zone of the telencephalon. Furthermore, the depletion of neural progenitor cells in PS cDKO embryos is due to NPCs exiting cell cycle and differentiating into neurons rather than reentering cell cycle between E13.5 and E14.5 following PS inactivation in most NPCs. The length of cell cycle, however, is unchanged in PS cDKO embryos. Expression of Notch target genes, Hes1 and Hes5, is significantly decreased in PS cDKO brains, whereas Dll1 expression is up-regulated, indicating that Notch signaling is effectively blocked by PS inactivation. These findings demonstrate that presenilins are essential for neural progenitor cells to re-enter cell cycle and thus ensure proper expansion of neural progenitor pool during embryonic neural development.

  2. Unmasking the responses of the stem cells and progenitors in the subventricular zone after neonatal and pediatric brain injuries

    Institute of Scientific and Technical Information of China (English)

    Mariano Guardia Clausi; Ekta Kumari; Steven W.Levison

    2016-01-01

    There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the subventricular zone (SVZ). However, a comprehensive understanding of SVZ cell responses to brain in-juries has been hindered by the lack of sensitive approaches to study the cellular composition of this niche. Here we review progress being made in deciphering the cells of the SVZ gleaned from the use of a recently designed lfow cytometry panel that allows SVZ cells to be parsed into multiple subsets of progenitors as well as putative stem cells. We review how this approach has begun to unmask both the heterogeneity of SVZ cells as well as the dynamic shifts in cell populations with neonatal and pediatric brain injuries. We also discuss how lfow cytometric analyses also have begun to reveal how speciifc cytokines, such as Leuke-mia inhibitory factor are coordinating SVZ responses to injury.

  3. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  4. Curative effect of transplantation of mesenchymal stem cells transfected with recombinant lentiviral vectors carrying brain-derived neurotrophic factor gene on intracerebral hemorrhage in rats

    Institute of Scientific and Technical Information of China (English)

    任瑞芳

    2013-01-01

    Objective To observe the curative effect of transplantation of mesenchymal stem cells(MSCs) transfected with recombinant lentiviral vectors carrying brain-derived neurotrophic factor(BDNF) gene on intracerebral

  5. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier.

    Science.gov (United States)

    Biancardi, Vinicia Campana; Son, Sook Jin; Ahmadi, Sahra; Filosa, Jessica A; Stern, Javier E

    2014-03-01

    Angiotensin II-mediated vascular brain inflammation emerged as a novel pathophysiological mechanism in neurogenic hypertension. However, the precise underlying mechanisms and functional consequences in relation to blood-brain barrier (BBB) integrity and central angiotensin II actions mediating neurohumoral activation in hypertension are poorly understood. Here, we aimed to determine whether BBB permeability within critical hypothalamic and brain stem regions involved in neurohumoral regulation was altered during hypertension. Using digital imaging quantification after intravascularly injected fluorescent dyes and immunohistochemistry, we found increased BBB permeability, along with altered key BBB protein constituents, in spontaneously hypertensive rats within the hypothalamic paraventricular nucleus, the nucleus of the solitary tract, and the rostral ventrolateral medulla, all critical brain regions known to contribute to neurohumoral activation during hypertension. BBB disruption, including increased permeability and downregulation of constituent proteins, was prevented in spontaneously hypertensive rats treated with the AT1 receptor antagonist losartan, but not with hydralazine, a direct vasodilator. Importantly, we found circulating angiotensin II to extravasate into these brain regions, colocalizing with neurons and microglial cells. Taken together, our studies reveal a novel angiotensin II-mediated feed-forward mechanism during hypertension, by which circulating angiotensin II evokes increased BBB permeability, facilitating in turn its access to critical brain regions known to participate in blood pressure regulation.

  6. Topiramate attenuates early brain injury following subarachnoid haemorrhage in rats via duplex protection against inflammation and neuronal cell death.

    Science.gov (United States)

    Tian, Yong; Guo, Song-Xue; Li, Jian-Ru; Du, Hang-Gen; Wang, Chao-Hui; Zhang, Jian-Min; Wu, Qun

    2015-10-05

    Early brain injury (EBI) following aneurysmal subarachnoid haemorrhage (SAH) insults contributes to the poor prognosis and high mortality observed in SAH patients. Topiramate (TPM) is a novel, broad-spectrum, antiepileptic drug with a reported protective effect against several brain injuries. The current study aimed to investigate the potential of TPM for neuroprotection against EBI after SAH and the possible dose-dependency of this effect. An endovascular perforation SAH model was established in rats, and TPM was administered by intraperitoneal injection after surgery at three different doses (20mg/kg, 40mg/kg, and 80mg/kg). The animals' neurological scores and brain water content were evaluated, and ELISA, Western blotting and immunostaining assays were conducted to assess the effect of TPM. The results revealed that TPM lowers the elevated levels of myeloperoxidase and proinflammatory mediators observed after SAH in a dose-related fashion, and the nuclear factor-kappa B (NF-κB) signalling pathway is the target of neuroinflammation regulation. In addition, TPM ameliorated SAH-induced cortical neuronal apoptosis by influencing Bax, Bcl-2 and cleaved caspase-3 protein expression, and the effect of TPM was enhanced in a dose-dependent manner. Various dosages of TPM also upregulated the protein expression of the γ-aminobutyric acid (GABA)-ergic signalling molecules, GABAA receptor (GABAAR) α1, GABAAR γ2, and K(+)-Cl(-) co-transporter 2 (KCC2) together and downregulated Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1) expression. Thus, TPM may be an effective neuroprotectant in EBI after SAH by regulating neuroinflammation and neuronal cell death.

  7. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    Directory of Open Access Journals (Sweden)

    Naoki Tajiri

    Full Text Available Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  8. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    Science.gov (United States)

    Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V

    2013-01-01

    Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  9. Neuroanesthesia management of neurosurgery of brain stem tumor requiring neurophysiology monitoring in an iMRI OT setting

    Directory of Open Access Journals (Sweden)

    Sabbagh Abdulrahman

    2009-01-01

    Full Text Available This report describes a rare case of ventrally exophytic pontine glioma describing operative and neuroanesthesia management. The combination of intraoperative neuromonitoring was used. It constituted: Brain stem evoked responses/potentials, Motor EP: recording from cranial nerve supplied muscle, and Sensory EP: Medial/tibial. Excision of the tumor was done with intra-operative magnatic resonance imaging (iMRI, which is considered a new modality.

  10. Repair of spinal cord injury by neural stem cells transfected with brain-derived neurotrophic factor-green fluorescent protein in rats A double effect of stem cells and growth factors

    Institute of Scientific and Technical Information of China (English)

    Yansong Wang; Gang Lü

    2010-01-01

    Brain-derived neurotrophic factor(BDNF)can significantly promote nerve regeneration and repair.High expression of the BDNF-green fluorescent protein(GFP)gene persists for a long time after transfection into neural stem cells.Nevertheless,little is known about the biological characteristics of BDNF-GFP modified nerve stem cells in vivo and their ability to induce BDNF expression or repair spinal cord injury.In the present study,we transplanted BDNF-GFP transgenic neural stem cells into a hemisection model of rats.Rats with BDNF-GFP stem cells exhibited significantly increased BDNF expression and better locomotor function compared with stem cells alone.Cellular therapy with BDNF-GFP transgenic stem cells can improve outcomes better than stem cells alone and may have therapeutic potential for spinal cord injury.

  11. Susceptibility-weighted imaging of the venous networks around the brain stem

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Ming; Lin, Zhong-Xiao; Zhang, Nu [Wenzhou Medical University, Department of Neurosurgery, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China); Zhang, Xiao-Fen; Qiao, Hui-Huang; Chen, Cheng-Chun [Wenzhou Medical University, Department of Human Anatomy, Wenzhou (China); Ren, Chuan-Gen; Li, Jian-Ce [Wenzhou Medical University, Department of Radiology, The 1nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China)

    2014-10-18

    The venous network of the brainstem is complex and significant. Susceptibility-weighted imaging (SWI) is a practical technique which is sensitive to veins, especially tiny veins. Our purpose of this study was to evaluate the visualization of the venous network of brainstem by using SWI at 3.0 T. The occurrence rate of each superficial veins of brainstem was evaluated by using SWI on a 3 T MR imaging system in 60 volunteers. The diameter of the lateral mesencephalic vein and peduncular vein were measured by SWI using the reconstructed mIP images in the sagittal view. And the outflow of the veins of brainstem were studied and described according to the reconstructed images. The median anterior pontomesencephalic vein, median anterior medullary vein, peduncular vein, right vein of the pontomesencephalic sulcus, and right lateral anterior pontomesencephalic vein were detected in all the subjects (100 %). The outer diameter of peduncular vein was 1.38 ± 0.26 mm (range 0.8-1.8 mm). The lateral mesencephalic vein was found in 75 % of the subjects and the mean outer diameter was 0.81 ± 0.2 mm (range 0.5-1.2 mm). The inner veins of mesencephalon were found by using SWI. The venous networks around the brain stem can be visualized by SWI clearly. This result can not only provide data for anatomical study, but also may be available for the surgical planning in the infratentorial region. (orig.)

  12. A developmental study of bone conduction auditory brain stem response in infants.

    Science.gov (United States)

    Yang, E Y; Rupert, A L; Moushegian, G

    1987-08-01

    Two studies, vibrator placement and masking, were performed to evaluate the developmental aspect of bone conduction auditory brain stem response (ABR) in human infants. Subject groups included newborns, 1-yr-olds, and adults. In the vibrator studies, ABRs were obtained from placements of the bone conduction vibrator on the frontal, occipital, and temporal bones. Results showed that temporal placements in neonates and 1-yr-olds produce significantly shorter wave V latencies of ABR than frontal or occipital placements. In adults, differences of wave V latencies from various vibrator placements were comparatively small. In the masking studies, ABRs were acquired from vibrator placements at the temporal bone in the presence of ipsilateral air conducted masking noise from the experimental groups. Results showed that interaural attenuations of bone conduction click stimuli are the largest in neonates, somewhat smaller from 1-yr-olds, and the smallest in adults. The findings of this research strongly suggest that temporal placements for bone conduction ABR should be used, in some instances, when testing infants and 1-yr-olds. The results of this study support the proposition that bone conduction ABR is a feasible and reliable diagnostic tool in testing infants.

  13. EphrinB3 restricts endogenous neural stem cell migration after traumatic brain injury.

    Science.gov (United States)

    Dixon, Kirsty J; Mier, Jose; Gajavelli, Shyam; Turbic, Alisa; Bullock, Ross; Turnley, Ann M; Liebl, Daniel J

    2016-11-01

    Traumatic brain injury (TBI) leads to a series of pathological events that can have profound influences on motor, sensory and cognitive functions. Conversely, TBI can also stimulate neural stem/progenitor cell proliferation leading to increased numbers of neuroblasts migrating outside their restrictive neurogenic zone to areas of damage in support of tissue integrity. Unfortunately, the factors that regulate migration are poorly understood. Here, we examine whether ephrinB3 functions to restrict neuroblasts from migrating outside the subventricular zone (SVZ) and rostral migratory stream (RMS). We have previously shown that ephrinB3 is expressed in tissues surrounding these regions, including the overlying corpus callosum (CC), and is reduced after controlled cortical impact (CCI) injury. Our current study takes advantage of ephrinB3 knockout mice to examine the influences of ephrinB3 on neuroblast migration into CC and cortex tissues after CCI injury. Both injury and/or ephrinB3 deficiency led to increased neuroblast numbers and enhanced migration outside the SVZ/RMS zones. Application of soluble ephrinB3-Fc molecules reduced neuroblast migration into the CC after injury and limited neuroblast chain migration in cultured SVZ explants. Our findings suggest that ephrinB3 expression in tissues surrounding neurogenic regions functions to restrict neuroblast migration outside the RMS by limiting chain migration.

  14. Subthreshold K+ Channel Dynamics Interact With Stimulus Spectrum to Influence Temporal Coding in an Auditory Brain Stem Model

    Science.gov (United States)

    Day, Mitchell L.; Doiron, Brent; Rinzel, John

    2013-01-01

    Neurons in the auditory brain stem encode signals with exceptional temporal precision. A low-threshold potassium current, IKLT, present in many auditory brain stem structures and thought to enhance temporal encoding, facilitates spike selection of rapid input current transients through an associated dynamic gate. Whether the dynamic nature of IKLT interacts with the timescales in spectrally rich input to influence spike encoding remains unclear. We examine the general influence of IKLT on spike encoding of stochastic stimuli using a pattern classification analysis between spike responses from a ventral cochlear nucleus (VCN) model containing IKLT, and the same model with the dynamics removed. The influence of IKLT on spike encoding depended on the spectral content of the current stimulus such that maximal IKLT influence occurred for stimuli with power concentrated at frequencies low enough (<500 Hz) to allow IKLT activation. Further, broadband stimuli significantly decreased the influence of IKLT on spike encoding, suggesting that broadband stimuli are not well suited for investigating the influence of some dynamic membrane nonlinearities. Finally, pattern classification on spike responses was performed for physiologically realistic conductance stimuli created from various sounds filtered through an auditory nerve (AN) model. Regardless of the sound, the synaptic input arriving at VCN had similar low-pass power spectra, which led to a large influence of IKLT on spike encoding, suggesting that the subthreshold dynamics of IKLT plays a significant role in shaping the response of real auditory brain stem neurons. PMID:18057115

  15. Does β-APP staining of the brain in infant bed-sharing deaths differentiate these cases from sudden infant death syndrome?

    DEFF Research Database (Denmark)

    Jensen, Lisbeth Lund; Banner, Jytte; Byard, Roger W

    2014-01-01

    Archival cerebral tissue from infants whose deaths were attributed to sudden infant death syndrome (SIDS) from South Australia and Western Denmark were stained for β-amyloid precursor protein (β-APP) and graded according to a simple scoring chart. The resulting APP scores were correlated...

  16. 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death.

    Science.gov (United States)

    Ray, Anasuya; Vasudevan, Smreti; Sengupta, Suparna

    2015-01-01

    Cancer stem cells (CSCs) pose a serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. In this study, we have investigated inhibitory activity of the ginger-derived compound 6-shogaol against breast cancer cells both in monolayer and in cancer-stem cell-like spheroid culture. The spheroids were generated from adherent breast cancer cells. 6-shogaol was effective in killing both breast cancer monolayer cells and spheroids at doses that were not toxic to noncancerous cells. The percentages of CD44+CD24-/low cells and the secondary sphere content were reduced drastically upon treatment with 6-shogaol confirming its action on CSCs. Treatment with 6-shogaol caused cytoplasmic vacuole formation and cleavage of microtubule associated protein Light Chain3 (LC3) in both monolayer and spheroid culture indicating that it induced autophagy. Kinetic analysis of the LC3 expression and a combination treatment with chloroquine revealed that the autophagic flux instigated cell death in 6-shogaol treated breast cancer cells in contrast to the autophagy inhibitor chloroquine. Furthermore, 6-shogaol-induced cell death got suppressed in the presence of chloroquine and a very low level of apoptosis was exhibited even after prolonged treatment of the compound, suggesting that autophagy is the major mode of cell death induced by 6-shogaol in breast cancer cells. 6-shogaol reduced the expression levels of Cleaved Notch1 and its target proteins Hes1 and Cyclin D1 in spheroids, and the reduction was further pronounced in the presence of a γ-secretase inhibitor. Secondary sphere formation in the presence of the inhibitor was also further reduced by 6-shogaol. Together, these results indicate that the inhibitory action of 6-shogaol on spheroid growth and sustainability is conferred through γ-secretase mediated down-regulation of Notch signaling. The efficacy of 6-shogaol in monolayer and cancer stem cell-like spheroids raise hope for its

  17. Scientific and ethical issues related to stem cell research and interventions in neurodegenerative disorders of the brain.

    Science.gov (United States)

    Barker, Roger A; de Beaufort, Inez

    2013-11-01

    Should patients with Parkinson's disease participate in research involving stem cell treatments? Are induced pluripotent stem cells (iPSC) the ethical solution to the moral issues regarding embryonic stem cells? How can we adapt trial designs to best assess small numbers of patients in receipt of invasive experimental therapies? Over the last 20 years there has been a revolution in our ability to make stem cells from different sources and use them for therapeutic gain in disorders of the brain. These cells, which are defined by their capacity to proliferate indefinitely as well as differentiate into selective phenotypic cell types, are viewed as being especially attractive for studying disease processes and for grafting in patients with chronic incurable neurodegenerative disorders of the CNS such as Parkinson's disease (PD). In this review we briefly discuss and summarise where our understanding of stem cell biology has taken us relative to the clinic and patients, before dealing with some of the major ethical issues that work of this nature generates. This includes issues to do with the source of the cells, their ownership and exploitation along with questions about patient recruitment, consent and trial design when they translate to the clinic for therapeutic use.

  18. Activated astrocytes enhance the dopaminergic differentiation of stem cells and promote brain repair through bFGF.

    Science.gov (United States)

    Yang, Fan; Liu, Yunhui; Tu, Jie; Wan, Jun; Zhang, Jie; Wu, Bifeng; Chen, Shanping; Zhou, Jiawei; Mu, Yangling; Wang, Liping

    2014-12-17

    Astrocytes provide neuroprotective effects against degeneration of dopaminergic (DA) neurons and play a fundamental role in DA differentiation of neural stem cells. Here we show that light illumination of astrocytes expressing engineered channelrhodopsin variant (ChETA) can remarkably enhance the release of basic fibroblast growth factor (bFGF) and significantly promote the DA differentiation of human embryonic stem cells (hESCs) in vitro. Light activation of transplanted astrocytes in the substantia nigra (SN) also upregulates bFGF levels in vivo and promotes the regenerative effects of co-transplanted stem cells. Importantly, upregulation of bFGF levels, by specific light activation of endogenous astrocytes in the SN, enhances the DA differentiation of transplanted stem cells and promotes brain repair in a mouse model of Parkinson's disease (PD). Our study indicates that astrocyte-derived bFGF is required for regulation of DA differentiation of the stem cells and may provide a strategy targeting astrocytes for treatment of PD.

  19. Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Hai-xiao Zhou; Zhi-gang Liu; Xiao-jiao Liu; Qian-xue Chen

    2016-01-01

    Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO) treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized lfuid (2.5–3.0 atm impact force). The injured rats were then administered UC-MSC transplantationvia the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function signiifcantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and signiifcantly promotes recovery of neurological functions.

  20. Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain.

    Science.gov (United States)

    Xing, Fei; Kobayashi, Aya; Okuda, Hiroshi; Watabe, Misako; Pai, Sudha K; Pandey, Puspa R; Hirota, Shigeru; Wilber, Andrew; Mo, Yin-Yuan; Moore, Brian E; Liu, Wen; Fukuda, Koji; Iiizumi, Megumi; Sharma, Sambad; Liu, Yin; Wu, Kerui; Peralta, Elizabeth; Watabe, Kounosuke

    2013-03-01

    Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the 1 year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastatic breast tumour cells in the brain highly expressed IL-1β which then 'activated' surrounding astrocytes. This activation significantly augmented the expression of JAG1 in the astrocytes, and the direct interaction of the reactivated astrocytes and cancer stem-like cells (CSCs) significantly stimulated Notch signalling in CSCs. We also found that the activated Notch signalling in CSCs up-regulated HES5 followed by promoting self-renewal of CSCs. Furthermore, we have shown that the blood-brain barrier permeable Notch inhibitor, Compound E, can significantly suppress the brain metastasis in vivo. These results represent a novel paradigm for the understanding of how metastatic breast CSCs re-establish their niche for their self-renewal in a totally different microenvironment, which opens a new avenue to identify a novel and specific target for the brain metastatic disease.

  1. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  2. Computed tomographic angiography criteria in the diagnosis of brain death - comparison of sensitivity and interobserver reliability of different evaluation scales

    Energy Technology Data Exchange (ETDEWEB)

    Sawicki, Marcin; Walecka, A. [Pomeranian Medical University, Department of Diagnostic Imaging and Interventional Radiology, Szczecin (Poland); Bohatyrewicz, R.; Solek-Pastuszka, J. [Pomeranian Medical University, Clinic of Anesthesiology and Intensive Care, Szczecin (Poland); Safranow, K. [Pomeranian Medical University, Department of Biochemistry and Medical Chemistry, Szczecin (Poland); Walecki, J. [The Centre of Postgraduate Medical Education, Warsaw (Poland); Rowinski, O. [Medical University of Warsaw, 2nd Department of Clinical Radiology, Warsaw (Poland); Czajkowski, Z. [Regional Joint Hospital, Szczecin (Poland); Guzinski, M. [Wroclaw Medical University, Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw (Poland); Burzynska, M. [Wroclaw Medical University, Department of Anesthesiology and Intensive Therapy, Wroclaw (Poland); Wojczal, J. [Medical University of Lublin, Department of Neurology, Lublin (Poland)

    2014-08-15

    The standardized diagnostic criteria for computed tomographic angiography (CTA) in diagnosis of brain death (BD) are not yet established. The aim of the study was to compare the sensitivity and interobserver agreement of the three previously used scales of CTA for the diagnosis of BD. Eighty-two clinically brain-dead patients underwent CTA with a delay of 40 s after contrast injection. Catheter angiography was used as the reference standard. CTA results were assessed by two radiologists, and the diagnosis of BD was established according to 10-, 7-, and 4-point scales. Catheter angiography confirmed the diagnosis of BD in all cases. Opacification of certain cerebral vessels as indicator of BD was highly sensitive: cortical segments of the middle cerebral artery (96.3 %), the internal cerebral vein (98.8 %), and the great cerebral vein (98.8 %). Other vessels were less sensitive: the pericallosal artery (74.4 %), cortical segments of the posterior cerebral artery (79.3 %), and the basilar artery (82.9 %). The sensitivities of the 10-, 7-, and 4-point scales were 67.1, 74.4, and 96.3 %, respectively (p < 0.001). Percentage interobserver agreement in diagnosis of BD reached 93 % for the 10-point scale, 89 % for the 7-point scale, and 95 % for the 4-point scale (p = 0.37). In the application of CTA to the diagnosis of BD, reducing the assessment of vascular opacification scale from a 10- to a 4-point scale significantly increases the sensitivity and maintains high interobserver reliability. (orig.)

  3. Protective Effects of Salubrinal on Liver Injury in Rat Models of Brain Death

    Institute of Scientific and Technical Information of China (English)

    Tao Wang; Shui-Jun Zhang; Sheng-Li Cao; Wen-Zhi Guo; Bing Yan; Hong-Bo Fang

    2015-01-01

    Background:Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats.In this study,we observed the effect ofsalubrinal (Sal,Sigma,USA) on liver cells in BD rats and explored its relevant mechanisms.Methods:Thirty Sprague-Dawley rats were equally randomized into three groups:BD group,Sal group,and DMSO group.The BD models were established by increasing intracranial pressure in a modified,slow,and intermittent way.In the drug groups,Sal was administered l h before the induction of BD.After modeling was completed,the blood and liver samples were harvested.CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction.PKR-like ER kinase (PERK),P-eukaryotic translation initiation factor 2α (eIF2α),eIF2α,CHOP and caspase-12 expression was detected using western blotting (WB).CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC).Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer.Hepatic cell apoptosis was detected using TUNEL.The results were analyzed using Quantity-one v4.62 software (Bio-Rad,USA).Results:CHOP and caspase-12 expression and PERK,eIF2α,and P-eIF2α protein expression showed no significant difference between BD group and DMSO group.Compared with BD group,Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P < 0.05).However,eIF2α expression showed no significant difference (P > 0.05).After the Sal treatment,CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P < 0.05).WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment.Sal was associated with improved liver function and decreased hepatic cell apoptosis.Conclusions:Sal can significantly reduce apoptosis in hepatic cells of BD rats

  4. Head Trauma with or without Mild Brain Injury Increases the Risk of Future Traumatic Death: A Controlled Prospective 15-Year Follow-Up Study.

    Science.gov (United States)

    Vaaramo, Kalle; Puljula, Jussi; Tetri, Sami; Juvela, Seppo; Hillbom, Matti

    2015-10-15

    Patients who have recovered from traumatic brain injury (TBI) show an increased risk of premature death. To investigate long-term mortality rates in a population admitted to the hospital for head injury (HI), we conducted a population-based prospective case-control, record-linkage study, All subjects who were living in Northern Ostrobothnia, and who were admitted to Oulu University Hospital in 1999 because of HI (n=737), and 2196 controls matched by age, gender, and residence randomly drawn from the population of Northern Ostrobothnia were included. Death rate and causes of death in HI subjects during 15 years of follow-up was compared with the general population controls. The crude mortality rates were 56.9, 18.6, and 23.8% for subjects having moderate-to-severe traumatic brain injury (TBI), mild TBI, and head injury without TBI, respectively. The corresponding approximate annual mortality rates were 6.7%, 1.4%, and 1.9%. All types of index HI predicted a significant risk of traumatic death in the future. Subjects who had HI without TBI had an increased risk of both death from all causes (hazard ratio 2.00; 95% confidence interval 1.57-2.55) and intentional or unintentional traumatic death (4.01, 2.20-7.30), compared with controls. The main founding was that even HI without TBI carries an increased risk of future traumatic death. The reason for this remains unknown and further studies are needed. To prevent such premature deaths, post-traumatic therapy should include an interview focusing on lifestyle factors.

  5. Study of brain-derived neurotrophic factor gene transgenic neural stem cells in the rat retina

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xue-mei; YUAN Hui-ping; WU Dong-lai; ZHOU Xin-rong; SUN Da-wei; LI Hong-yi; SHAO Zheng-bo

    2009-01-01

    Background Neural stem cells (NSCs) transplantation and gene therapy have been widely investigated for treating the cerebullar and myelonic injuries, however, studies on the ophthalmology are rare. The aim of this study was to investigate the migration and differentiation of brain-derived neurotrophic factor (BDNF) gene transgenic NSCs transplanted into the normal rat retinas. Methods NSCs were cultured and purified in vitro and infected with recombinant retrovirus pLXSN-BDNF and pLXSN respectively, to obtain the BDNF overexpressed NSCs (BDNF-NSCs) and control cells (p-NSCs). The expression of BDNF genes in two transgenic NSCs and untreated NSCs were measured by fluorescent quantitative polymerase chain reaction (FQ-PCR) and enzyme-linked immunosorbent assay (ELISA). BDNF-NSCs and NSCs were infected with adeno-associated viruses-enhanced green fluorescent protein (AAV-EGFP) to track them in vivo and served as donor cells for transplantation into the subretinal space of normal rat retinas, phosphated buffer solution (PBS) served as pseudo transplantation for a negative control. Survival, migration, and differentiation of donor cells in host retinas were observed and analyzed with Heidelberg retina angiograph (HRA) and immunohistochemistry, respectively. Results NSCs were purified successfully by limiting dilution assay. The expression of BDNF gene in BDNF-NSCs was the highest among three groups both at mRNA level tested by FQ-PCR (P<0.05) and at protein level measured by ELISA (P<0.05), which showed that BDNF was overexpressed in BDNF-NSCs. The results of HRA demonstrated that graft cells could survive well and migrate into the host retinas, while the immunohistochemical analysis revealed that transplanted BDNF-NSCs differentiated into neuron more efficiently compared with the control NSCs 2 months after transplantation. Conclusions The seed cells of NSCs highly secreting BDNF were established. BDNF can promote NSCs to migrate and differentiate into neural cells in

  6. Brain death provokes very acute alteration in myocardial morphology detected by echocardiography: preventive effect of beta-blockers.

    Science.gov (United States)

    Ferrera, René; Hadour, Guylaine; Tamion, Fabienne; Henry, Jean-Paul; Mulder, Paul; Richard, Vincent; Thuillez, Christian; Ovize, Michel; Derumeaux, Geneviève

    2011-03-01

    Our objective was to evaluate immediate acute changes in myocardial function during the autonomic storm of brain death (BD). Wistar rats were divided into four groups (n = 8/group): controls without any treatment, β-blocker (Esmolol®, 10 mg/kg), calcium channel blocker (Diltiazem®, 10 mg/kg), or alpha-blocker (Prazosin®, 0.3 mg/kg). Treatments were administered intravenously 5 min before BD induction. Echocardiography (ATL-5000, 8 MHz) was performed to measure left ventricular (LV) dimensions and fractional shortening at baseline, during BD induction and 5 min and 15 min after BD. In controls, BD was immediately associated with an increase in wall thickness and a decrease in LV cavity dimension. This myocardial wall hypertrophy was completely prevented by β-blockers, but not with calcium- and alpha-blockers. Extensive myocardial interstitial edema was found in all groups, except in the β-blocker group. Myocardial wall hypertrophy was also prevented during a longer follow-up of 180 min after BD in β-blocker group as opposed to controls. In conclusion, BD is associated with an immediate and severe myocardial damage related to an important interstitial edema which is prevented by β-blockers.

  7. Predictive factors of brain death in severe stroke patients identified by organ procurement and transplant coordination in Lorrain, France.

    Science.gov (United States)

    Humbertjean, Lisa; Mione, Gioia; Fay, Renaud; Durin, Laurent; Planel, Sophie; Lacour, Jean-Christophe; Enea, Ana-Maria; Richard, Sébastien

    2016-03-01

    There are no established predictive factors to identify patients at the acute phase of severe stroke with a high probability of presenting brain death (BD). We retrospectively collected clinical and paraclinical data of consecutive patients at the acute phase of severe stroke with a potential progression to BD through the hospital organ procurement and transplant coordination system in five centres in Lorrain (France) between 1 January 2012 and 31 December 2013. Final endpoint was adjudicated BD. Of 400 included patients, 91 (23%) presented adjudicated BD. Initial Glasgow Coma Scale score ≤6 (P = 0.008), herniation (P = 0.009), hydrocephalus (P = 0.019), initial systolic blood pressure >150 mmHg (P = 0.002), past history of alcohol abuse (P = 0.019) and stroke volume >65 ml (P = 0.040) were significantly associated with BD progression. Two prognostic scores for stroke with unquantifiable or quantifiable volume were built according to the number of risk factors presented. Following internal validation, the respective bias-corrected predictive performance (c-index) of the two scores was 72% (95% confidence interval: 67-78%) and 77% (95% confidence interval: 72-82%). These scores could form the basis of a simple tool of six criteria to help physicians make the difficult decision of intensive care unit management to preserve organs in potential donors.

  8. Nanoparticle-based CT imaging technique for longitudinal and quantitative stem cell tracking within the brain: application in neuropsychiatric disorders.

    Science.gov (United States)

    Betzer, Oshra; Shwartz, Amit; Motiei, Menachem; Kazimirsky, Gila; Gispan, Iris; Damti, Efrat; Brodie, Chaya; Yadid, Gal; Popovtzer, Rachela

    2014-09-23

    A critical problem in the development and implementation of stem cell-based therapy is the lack of reliable, noninvasive means to image and trace the cells post-transplantation and evaluate their biodistribution, final fate, and functionality. In this study, we developed a gold nanoparticle-based CT imaging technique for longitudinal mesenchymal stem cell (MSC) tracking within the brain. We applied this technique for noninvasive monitoring of MSCs transplanted in a rat model for depression. Our research reveals that cell therapy is a potential approach for treating neuropsychiatric disorders. Our results, which demonstrate that cell migration could be detected as early as 24 h and up to one month post-transplantation, revealed that MSCs specifically navigated and homed to distinct depression-related brain regions. We further developed a noninvasive quantitative CT ruler, which can be used to determine the number of cells residing in a specific brain region, without tissue destruction or animal scarification. This technique may have a transformative effect on cellular therapy, both for basic research and clinical applications.

  9. EZH2 Protects Glioma Stem Cells from Radiation-Induced Cell Death in a MELK/FOXM1-Dependent Manner

    DEFF Research Database (Denmark)

    Kim, Sung-Hak; Joshi, Kaushal; Ezhilarasan, Ravesanker;

    2015-01-01

    Glioblastoma (GBM)-derived tumorigenic stem-like cells (GSCs) may play a key role in therapy resistance. Previously, we reported that the mitotic kinase MELK binds and phosphorylates the oncogenic transcription factor FOXM1 in GSCs. Here, we demonstrate that the catalytic subunit of Polycomb...

  10. Deletion of apolipoprotein E receptor-2 in mice lowers brain selenium and causes severe neurological dysfunction and death when a low-selenium diet is fed.

    Science.gov (United States)

    Burk, Raymond F; Hill, Kristina E; Olson, Gary E; Weeber, Edwin J; Motley, Amy K; Winfrey, Virginia P; Austin, Lori M

    2007-06-01

    Selenoprotein P (Sepp1) is a plasma and extracellular protein that is rich in selenium. Deletion of Sepp1 results in sharp decreases of selenium levels in the brain and testis with dysfunction of those organs. Deletion of Sepp1 also causes increased urinary selenium excretion, leading to moderate depletion of whole-body selenium. The lipoprotein receptor apolipoprotein E receptor-2 (apoER2) binds Sepp1 and facilitates its uptake by Sertoli cells, thus providing selenium for spermatogenesis. Experiments were performed to assess the effect of apoER2 on the concentration and function of selenium in the brain and on whole-body selenium. ApoER2-/- and apoER2+/+ male mice were fed a semipurified diet with selenite added as the source of selenium. ApoER2-/- mice had depressed brain and testis selenium, but normal levels in liver, kidney, muscle, and the whole body. Feeding a selenium-deficient diet to apoER2-/- mice led to neurological dysfunction and death, with some of the characteristics exhibited by Sepp1-/- mice fed the same diet. Thus, although it does not affect whole-body selenium, apoER2 is necessary for maintenance of brain selenium and for prevention of neurological dysfunction and death under conditions of selenium deficiency, suggesting an interaction of apoER2 with Sepp1 in the brain.

  11. Comparing Outcomes of Donation After Cardiac Death Versus Donation After Brain Death in Liver Transplant Recipients with Hepatitis C: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Malcolm Wells

    2014-01-01

    Full Text Available BACKGROUND: Liver transplantation (LT using organs donated after cardiac death (DCD is increasing due, in large part, to a shortage of organs. The outcome of using DCD organs in recipients with hepatits C virus (HCV infection remains unclear due to the limited experience and number of publications addressing this issue.

  12. CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.

    Directory of Open Access Journals (Sweden)

    Mayumi Jijiwa

    Full Text Available Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6 in BTSC of a subset of glioblastoma multiforme (GBM. Patients with CD44(high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high GBM but not from CD44(low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN, increased expression of phosphorylated AKT in CD44(high GBM, but not in CD44(low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway.

  13. Brain stem gliosarcoma in pediatric patient: a case report; Gliossarcoma de tronco cerebral em paciente pediatrico: relato de caso

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Roger Klein; Koppe, Daniela; Zignani, Juliana [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Faculdade de Medicina; Marconato, Marlon Cesar [Santa Maria Univ., RS (Brazil). Faculdade de Medicina; Abreu, Marcelo; Pitrez, Eduardo; Furtado, Alvaro Porto Alegre [Hospital das Clinicas, Porto Alegre, RS (Brazil). Servico de Radiologia

    2004-02-01

    The authors report a case of a white four year old boy with progressive neurological symptoms due to a brain stem mass lesion identified by computed tomography and magnetic resonance imaging scans. The diagnosis of gliosarcoma was confirmed by histological examination. This rare type of central nervous systems tumor affects mainly patients over 40 year of age and is most commonly supratentorial. Only a few cases of gliosarcoma in children have been reported, particularly int the infratentorial region. The epidemiological data as well as the most frequent computed tomography and magnetic resonance imaging findings are discussed. (author)

  14. 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death.

    Directory of Open Access Journals (Sweden)

    Anasuya Ray

    Full Text Available Cancer stem cells (CSCs pose a serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. In this study, we have investigated inhibitory activity of the ginger-derived compound 6-shogaol against breast cancer cells both in monolayer and in cancer-stem cell-like spheroid culture. The spheroids were generated from adherent breast cancer cells. 6-shogaol was effective in killing both breast cancer monolayer cells and spheroids at doses that were not toxic to noncancerous cells. The percentages of CD44+CD24-/low cells and the secondary sphere content were reduced drastically upon treatment with 6-shogaol confirming its action on CSCs. Treatment with 6-shogaol caused cytoplasmic vacuole formation and cleavage of microtubule associated protein Light Chain3 (LC3 in both monolayer and spheroid culture indicating that it induced autophagy. Kinetic analysis of the LC3 expression and a combination treatment with chloroquine revealed that the autophagic flux instigated cell death in 6-shogaol treated breast cancer cells in contrast to the autophagy inhibitor chloroquine. Furthermore, 6-shogaol-induced cell death got suppressed in the presence of chloroquine and a very low level of apoptosis was exhibited even after prolonged treatment of the compound, suggesting that autophagy is the major mode of cell death induced by 6-shogaol in breast cancer cells. 6-shogaol reduced the expression levels of Cleaved Notch1 and its target proteins Hes1 and Cyclin D1 in spheroids, and the reduction was further pronounced in the presence of a γ-secretase inhibitor. Secondary sphere formation in the presence of the inhibitor was also further reduced by 6-shogaol. Together, these results indicate that the inhibitory action of 6-shogaol on spheroid growth and sustainability is conferred through γ-secretase mediated down-regulation of Notch signaling. The efficacy of 6-shogaol in monolayer and cancer stem cell-like spheroids raise

  15. Brain-derived neurotrophic factor, but not neurotrophin-3, prevents ischaemia-induced neuronal cell death in organotypic rat hippocampal slice cultures.

    Science.gov (United States)

    Pringle, A K; Sundstrom, L E; Wilde, G J; Williams, L R; Iannotti, F

    1996-06-28

    We have investigated the neuroprotective actions of neurotrophins in a model of ischaemia using slice cultures. Ischaemia was induced in organotypic hippocampal cultures by simultaneous oxygen and glucose deprivation. Cell death was assessed 24 h later by propidium iodide fluorescence. Pre- but not post-ischaemic addition of brain-derived neurotrophic factor (BDNF) produced a concentration-dependent reduction in neuronal damage. Neurotrophin-3 was not neuroprotective. These data suggest that BDNF may form part of an endogenous neuroprotective mechanism.

  16. TYPE-2 DIABETES MELLITUS AND BRAIN STEM EVOKED RESPONSE AUDIOMETRY: A CASE CONTROL STUDY

    Directory of Open Access Journals (Sweden)

    Praveen S

    2016-01-01

    Full Text Available BACKGROUND AND OBJECTIVE Type-2 Diabetes Mellitus (T2DM causes pathophysiological changes in multiple organ system. The peripheral, autonomic and central neuropathy is known to occur in T2DM, which can be studied electrophysiologically. AIM Present study is aimed to evaluate functional integrity of auditory pathway in T2DM by Brainstem Evoked Response Audiometry (BERA. MATERIAL AND METHOD In the present case control study, BERA was recorded from the scalp of 20 T2DM patients aged 30-65 years and were compared with age matched 20 healthy controls. The BERA was performed using EMG Octopus, Clarity Medical Pvt. Ltd. The latencies of wave I, III, V and Wave I-III, I-V and III-V interpeak latencies of both right and left ear were recorded at 70dBHL. STATISTICAL RESULT AND USE Mean±SD of latencies of wave I, III, V and interpeak latency of I-III, I-V and III-V were estimated of T2DM and healthy controls. The significant differences between the two groups were assessed using unpaired student ‘t’ test for T2DM and control groups using GraphPad QuickCalcs calculator. P value <0.05 was considered to be significant. RESULT In T2DM BERA study revealed statistically significant (p<0.05 prolonged latencies of wave I, III and V in both right (1.81±0.33ms, 3.96±0.32ms, 5.60±0.25ms and left (1.96±0.24ms, 3.79±0.22ms, 5.67±0.25ms ear as compared to controls at 70dB. Wave III-V interpeak latency of left ear (1.87±0.31, 1.85±0.41ms and wave I-III (2.51±0.42ms, 1.96±0.48ms and III-V (2.01±0.43ms, 1.76±0.45ms of right ear was prolonged in diabetic patient as compared to controls, although no significant difference was obtained (p<0.05. INTERPRETATION AND CONCLUSION Increase in absolute latencies and interpeak latencies inT2DM patients suggest involvement of central neuronal axis at the level of brain stem and midbrain.

  17. Survival and death of epiblast cells during embryonic stem cell derivation revealed by long-term live-cell imaging with an Oct4 reporter system.

    Science.gov (United States)

    Yamagata, Kazuo; Ueda, Jun; Mizutani, Eiji; Saitou, Mitinori; Wakayama, Teruhiko

    2010-10-01

    Despite the broad literature on embryonic stem cells (ESCs), their derivation process remains enigmatic. This may be because of the lack of experimental systems that can monitor this prolonged cellular process. Here we applied a live-cell imaging technique to monitor the process of ESC derivation over 10 days from morula to outgrowth phase using an Oct4/eGFP reporter system. Our imaging reflects the 'natural' state of ESC derivation, as the ESCs established after the imaging were both competent in chimeric mice formation and germ-line transmission. Using this technique, ESC derivation in conventional conditions was imaged. After the blastocoel was formed, the intensity of Oct4 signals attenuated in the trophoblast cells but was maintained in the inner cell mass (ICM). Thereafter, the Oct4-positive cells scattered and their number decreased along with apoptosis of the other Oct4-nagative cells likely corresponds to trophoblast and hypoblast cells, and then only the surviving Oct4-positive cells proliferated and formed the colony. All embryos without exception passed through this cell death phase. Importantly, the addition of caspase inhibitor Z-VAD-FMK to the medium dramatically suppressed the loss of Oct4-positive cells and also other embryo-derived cells, suggesting that the cell deaths was induced by a caspase-dependent apoptotic pathway. Next we imaged the ESC derivation in 3i medium, which consists of chemical compounds that can suppress differentiation. The most significant difference between the conventional and 3i methods was that there was no obvious cell death in 3i, so that the colony formation was rapid and all of the Oct4-positive cells contributed to the formation of the outgrown colony. These data indicate that the prevention of cell death in epiblast cells is one of the important events for the successful establishment of ESCs. Thus, our imaging technique can advance the understanding of the time-dependent cellular changes during ESC derivation.

  18. Inflammation Following Traumatic Brain Injury in Humans: Insights from Data-Driven and Mechanistic Models into Survival and Death

    Science.gov (United States)

    Abboud, Andrew; Mi, Qi; Puccio, Ava; Okonkwo, David; Buliga, Marius; Constantine, Gregory; Vodovotz, Yoram

    2016-01-01

    Inflammation induced by traumatic brain injury (TBI) is a complex mediator of morbidity and mortality. We have previously demonstrated the utility of both data-driven and mechanistic models in settings of traumatic injury. We hypothesized that differential dynamic inflammation programs characterize TBI survivors vs. non-survivors, and sought to leverage computational modeling to derive novel insights into this life/death bifurcation. Thirteen inflammatory cytokines and chemokines were determined using Luminex™ in serial cerebrospinal fluid (CSF) samples from 31 TBI patients over 5 days. In this cohort, 5 were non-survivors (Glasgow Outcome Scale [GOS] score = 1) and 26 were survivors (GOS > 1). A Pearson correlation analysis of initial injury (Glasgow Coma Scale [GCS]) vs. GOS suggested that survivors and non-survivors had distinct clinical response trajectories to injury. Statistically significant differences in interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, and tumor necrosis factor-α (TNF-α) were observed between TBI survivors vs. non-survivors over 5 days. Principal Component Analysis and Dynamic Bayesian Network inference suggested differential roles of chemokines, TNF-α, IL-6, and IL-10, based upon which an ordinary differential equation model of TBI was generated. This model was calibrated separately to the time course data of TBI survivors vs. non-survivors as a function of initial GCS. Analysis of parameter values in ensembles of simulations from these models suggested differences in microglial and damage responses in TBI survivors vs. non-survivors. These studies suggest the utility of combined data-driven and mechanistic models in the context of human TBI. PMID:27729864

  19. Inflammation Following Traumatic Brain Injury in Humans: Insights from Data-Driven and Mechanistic Models into Survival and Death

    Directory of Open Access Journals (Sweden)

    Andrew Abboud

    2016-09-01

    Full Text Available Inflammation induced by traumatic brain injury (TBI is a complex mediator of morbidity and mortality. We have previously demonstrated the utility of both data-driven and mechanistic models in settings of traumatic injury. We hypothesized that differential dynamic inflammation programs characterize TBI survivors vs. non-survivors, and sought to leverage computational modeling to derive novel insights into this life/death bifurcation. Thirteen inflammatory cytokines and chemokines were determined using Luminex™ in serial cerebrospinal fluid (CSF samples from 31 TBI patients over 5 days. In this cohort, 5 were non-survivors (Glasgow Outcome Scale [GOS] score = 1 and 26 were survivors (GOS > 1. A Pearson correlation analysis of initial injury (Glasgow Coma Scale [GCS] vs. GOS suggested that survivors and non-survivors had distinct clinical response trajectories to injury. Statistically significant differences in interleukin (IL-4, IL-5, IL-6, IL-8, IL-13, and tumor necrosis factor-α (TNF-α were observed between TBI survivors vs. non-survivors over 5 days. Principal Component Analysis and Dynamic Bayesian Network inference suggested differential roles of chemokines, TNF-α, IL-6, and IL-10, based upon which an ordinary differential equation model of TBI was generated. This model was calibrated separately to the time course data of TBI survivors vs. non-survivors as a function of initial GCS. Analysis of parameter values in ensembles of simulations from these models suggested differences in microglial and damage responses in TBI survivors vs. non-survivors. These studies suggest the utility of combined data-driven and mechanistic models in the context of human TBI.

  20. Facilitated Anion Transport Induces Hyperpolarization of the Cell Membrane That Triggers Differentiation and Cell Death in Cancer Stem Cells.

    Science.gov (United States)

    Soto-Cerrato, Vanessa; Manuel-Manresa, Pilar; Hernando, Elsa; Calabuig-Fariñas, Silvia; Martínez-Romero, Alicia; Fernández-Dueñas, Víctor; Sahlholm, Kristoffer; Knöpfel, Thomas; García-Valverde, María; Rodilla, Ananda M; Jantus-Lewintre, Eloisa; Farràs, Rosa; Ciruela, Francisco; Pérez-Tomás, Ricardo; Quesada, Roberto

    2015-12-23

    Facilitated anion transport potentially represents a powerful tool to modulate various cellular functions. However, research into the biological effects of small molecule anionophores is still at an early stage. Here we have used two potent anionophore molecules inspired in the structure of marine metabolites tambjamines to gain insight into the effect induced by these compounds at the cellular level. We show how active anionophores, capable of facilitating the transmembrane transport of chloride and bicarbonate in model phospholipid liposomes, induce acidification of the cytosol and hyperpolarization of plasma cell membranes. We demonstrate how this combined effect can be used against cancer stem cells (CSCs). Hyperpolarization of cell membrane induces cell differentiation and loss of stemness of CSCs leading to effective elimination of this cancer cell subpopulation.

  1. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources

    Science.gov (United States)

    Lippmann, Ethan S.; Al-Ahmad, Abraham; Azarin, Samira M.; Palecek, Sean P.; Shusta, Eric V.

    2014-02-01

    Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm2). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.

  2. Brain-derived neurotrophic factor induces neuron-like cellular differentiation of mesenchymal stem cells derived from human umbilical cord blood cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Lei Chen; Guozhen Hui; Zhongguo Zhang; Bing Chen; Xiaozhi Liu; Zhenlin Liu; Hongliang Liu; Gang Li; Zhiguo Su; Junfei Wang

    2011-01-01

    Human umbilical cord blood was collected from full-term deliveries scheduled for cesarean section. Mononuclear cells were isolated, amplified and induced as mesenchymal stem cells. Isolated mesenchymal stem cells tested positive for the marker CD29, CD44 and CD105 and negative for typical hematopoietic and endothelial markers. Following treatment with neural induction medium containing brain-derived neurotrophic factor for 7 days, the adherent cells exhibited neuron-like cellular morphology. Immunohistochemical staining and reverse transcription-PCR revealed that the induced mesenchymal stem cells expressed the markers for neuron-specific enolase and neurofilament. The results demonstrated that human umbilical cord blood-derived mesenchymal stem cells can differentiate into neuron-like cells induced by brain-derived neurotrophic factor in vitro.

  3. Conditioned medium from mesenchymal stem cells induces cell death in organotypic cultures of rat hippocampus and aggravates lesion in a model of oxygen and glucose deprivation.

    Science.gov (United States)

    Horn, Ana Paula; Frozza, Rudimar Luiz; Grudzinski, Patrícia Benke; Gerhardt, Daniéli; Hoppe, Juliana Bender; Bruno, Alessandra Nejar; Chagastelles, Pedro; Nardi, Nance Beyer; Lenz, Guido; Salbego, Christianne

    2009-01-01

    Cell therapy using bone marrow-derived mesenchymal stem cells (MSC) seems to be a new alternative for the treatment of neurological diseases, including stroke. In order to investigate the response of hippocampal tissue to factors secreted by MSC and if these factors are neuroprotective in a model of oxygen and glucose deprivation (OGD), we used organotypic hippocampal cultures exposed to conditioned medium from bone marrow-derived MSC. Our results suggest that the conditioned medium obtained from these cells aggravates lesion caused by OGD. In addition, the presence of the conditioned medium alone was toxic mainly to cells in the CA1, CA2 and CA3 areas of the hippocampal organotypic culture even in basal conditions. GABA stimulation and NMDA and AMPA receptors antagonists were able to reduce propidium iodide staining, suggesting that the cell death induced by the toxic factors secreted by MSC could involve these receptors.

  4. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa;

    2008-01-01

    Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

  5. β-Amyloid precursor protein: function in stem cell development and Alzheimer's disease brain.

    Science.gov (United States)

    Small, David H; Hu, Yanling; Bolós, Marta; Dawkins, Edgar; Foa, Lisa; Young, Kaylene M

    2014-01-01

    Stem cell therapy may be a suitable approach for the treatment of many neurodegenerative diseases. However, one major impediment to the development of successful cell-based therapies is our limited understanding of the mechanisms that instruct neural stem cell behaviour, such as proliferation and cell fate specification. The β-amyloid precursor protein (APP) of Alzheimer's disease (AD) may play an important role in neural stem cell proliferation and differentiation. Our recent work shows that in vitro, APP stimulates neural stem or progenitor cell proliferation and neuronal differentiation. The effect on proliferation is mediated by an autocrine factor that we have identified as cystatin C. As cystatin C expression is also reported to inhibit the development of amyloid pathology in APP transgenic mice, our finding has implications for the possible use of cystatin C for the therapy of AD.

  6. Brain, Behavior, and Immunity: Biobehavioral influences on recovery following hematopoietic stem cell transplantation

    Science.gov (United States)

    Review of hematopoietic stem cell transplantation and its potential “window of opportunity” during which interventions targeting stress-related behavioral factors can influence the survival, health, and well-being of recipients.

  7. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells.

    Science.gov (United States)

    Castillo-Melendez, Margie; Yawno, Tamara; Jenkin, Graham; Miller, Suzanne L

    2013-10-24

    In the research, clinical, and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however, this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical, and logistical considerations, together with the propensity for native cells to form teratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs), or umbilical cord blood (UCB) stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  8. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

    Directory of Open Access Journals (Sweden)

    Margie eCastillo-Melendez

    2013-10-01

    Full Text Available In the research, clinical and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical and logistical considerations, together with the propensity for native cells to form terratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs, or umbilical cord blood (UCB stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells and mesenchymal stem cells, and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  9. Progress and prospects in neurorehabilitation: clinical applications of stem cells and brain-computer interface for spinal cord lesions.

    Science.gov (United States)

    Gongora, Mariana; Peressutti, Caroline; Machado, Sergio; Teixeira, Silmar; Velasques, Bruna; Ribeiro, Pedro

    2013-04-01

    Spinal cord injury (SCI) is a disease that affects millions of people worldwide, causing a temporary or permanent impairment of neuromotor functions. Mostly associated to traumatic lesions, but also to other forms of disease, the appropriate treatment is still unsure. In this review, several ongoing studies are presented that aim to provide methods of prevention that ensure quality of life, and rehabilitation trends to patients who suffer from this injury. Stem cell research, highlighted in this review, seeks to reduce damage caused to the tissue, as also provide spinal cord regeneration through the application of several types of stem cells. On the other hand, research using brain-computer interface (BCI) technology proposes the development of interfaces based on the interaction of neural networks with artificial tools to restore motor control and full mobility of the injured area. PubMed, MEDLINE and SciELO data basis analyses were performed to identify studies published from 2000 to date, which describe the link between SCI with stem cells and BCI technology.

  10. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  11. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

    Science.gov (United States)

    Nih, Lina R; Moshayedi, Pouria; Llorente, Irene L; Berg, Andrew R; Cinkornpumin, Jessica; Lowry, William E; Segura, Tatiana; Carmichael, S Thomas

    2017-02-01

    This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.

  12. Mitochondrial division inhibitor 1 (Mdivi-1) offers neuroprotection through diminishing cell death and improving functional outcome in a mouse model of traumatic brain injury.

    Science.gov (United States)

    Wu, Qiong; Xia, Shui-Xiu; Li, Qian-Qian; Gao, Yuan; Shen, Xi; Ma, Lu; Zhang, Ming-Yang; Wang, Tao; Li, Yong-Sheng; Wang, Zu-Feng; Luo, Cheng-Liang; Tao, Lu-Yang

    2016-01-01

    Mitochondria dysfunction, an enormous potential crisis, has attracted increasing attention. Disturbed regulation of mitochondrial dynamics, the balance of mitochondrial fusion and fission, has been implicated in neurodegenerative diseases, such as Parkinson׳s disease and cerebral ischemia/reperfusion. However the role of mitochondrial dynamics in traumatic brain injury (TBI) has not been illuminated. The aim of the present study was to investigate the role of Mdivi-1, a small molecule inhibitor of a key mitochondrial fission protein dynamin-related protein 1 (Drp1), in TBI-induced cell death and functional outcome deficits. Protein expression of Drp1 was first investigated. Outcome parameters consist of motor test, Morris water maze, brain edema and lesion volume. Cell death was detected by propidium iodide (PI) labeling, and mitochondrial morphology was assessed using transmission electron microscopy. In addition, the expression of apoptosis-related proteins cytochrome c (cyt-c) and caspase-3 was investigated. Our findings showed that up-regulation of Drp1 expression started at 1h post-TBI and peaked at 24 h, but inhibition of Drp1 by Mdivi-1 significantly alleviated TBI-induced behavioral deficits and brain edema, reduced morphological change of mitochondria, and decreased TBI-induced cell death together with lesion volume. Moreover, treatment with Mdivi-1 remarkably inhibited TBI-induced the release of cyt-c from mitochondria to cytoplasm, and activation of caspase-3 at 24 h after TBI. Taken together, these data imply that inhibition of Drp1 may help attenuate TBI-induced functional outcome and cell death through maintaining normal mitochondrial morphology and inhibiting activation of apoptosis.

  13. Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes alpha7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons.

    Science.gov (United States)

    Hruska, Martin; Keefe, Julie; Wert, David; Tekinay, Ayse Begum; Hulce, Jonathan J; Ibañez-Tallon, Ines; Nishi, Rae

    2009-11-25

    Vertebrate alpha-bungarotoxin-like molecules of the Ly-6 superfamily have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouse lynx1 and lynx2. One of these genes, an ortholog of prostate stem cell antigen (psca), is barely detectable at embryonic day (E) 8, before neuronal cell loss in the ciliary ganglion, but increases >100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of alpha7-containing nicotinic acetylcholine receptors (alpha7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks alpha7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of alpha7 signaling-induced cell death during development.

  14. 无心跳脑死亡兔模型的建立及生命体征变化%The changes of vital signs from establishment of gradual onset brain death rabbit model to cardiac death

    Institute of Scientific and Technical Information of China (English)

    范晓礼; 叶啟发; 钟自彪; 张远; 乔兵兵; 赵杰

    2013-01-01

    Objective To observe changes of vital signs from