Sounds promising for stroke. Next steps?
Has your stroke doctor and hospital done ONE DAMN THING to initiate further research? Or it is not their responsibility?
Are your doctor and stroke hospital being responsible and doing any followup to get research going?
Our fucking failures of stroke associations will DO NOTHING. Your doctor will DO NOTHING. Your stroke hospital will DO NOTHING. You're screwed.
Or will NOTHING BE DONE since everyone in stroke is
waiting for SOMEONE ELSE TO SOLVE THE PROBLEM?
And why are they doing nothing?
Laziness? Incompetence? Or just don't care? No leadership? No strategy? Not my job? The board of directors didn't tell them that totally solving stroke was their job, not just lazily relying on the status quo?
Circulation, Cell Functions Restored in Pig Brains After Death
Experiment raises ethical questions for animals -- and for humans
Nature, though they emphasized that this came nowhere close to reviving global brain functioning.
An artificial perfusion system known as BrainEx was able to reduce cell death and restore microcirculation and certain molecular and cellular functions in pig brains up to 4 hours postmortem, reported Nenad Sestan, MD, PhD, of Yale School of Medicine in New Haven, Connecticut, and colleagues.
The brains showed no evidence of organized, global electrical activity associated with awareness or perception, the researchers added.
"This is not a living brain, but a cellularly active brain," Sestan said in a press conference. "These findings lay the groundwork for novel approaches to studying the postmortem brain and potentially restoring the function of damaged cells within the diseased brain." Stroke treatment and recovery is perhaps the most important application of the research.
The research, supported by the NIH BRAIN Initiative, is "a real breakthrough for brain research" and had never been done before in a large, intact mammalian brain, noted Andrea Beckel-Mitchener, PhD, BRAIN Initiative Team Lead.
"It's quite a surprising result," Beckel-Mitchener said in an NIH press briefing. "We did not know that brain cells were this resilient, and under the right conditions -- such as what's been shown here with BrainEx -- that the cells could maintain some healthy function hours after loss of blood flow."
Cell death, clotting of small blood vessels, and other processes that degrade brain tissue after death have hampered researchers' ability to study a large intact postmortem brain. To overcome these limitations, Sestan and colleagues created BrainEx -- essentially, a high-tech pumping system coupled with a proprietary perfusate.
"The brain is highly sensitive to changes in oxygen levels and interruptions in blood flow," Sestan said. "However, multiple observations from our lab and others have questioned the notion that widespread cell death is unavoidable minutes, or even hours, after blood flow stops."
"For example, live cells can be harvested from postmortem brains and cultured in a dish," he continued. "This indicates that cells in the postmortem brain may still have the capacity to be revived."
In this study, the researchers placed 32 pig brains from a local pork-processing plant in the BrainEx system 4 hours after death. The brains were perfused at normal body temperature (37 degrees Celsius) for 6 hours.
BrainEx brains showed reduced cell death, preserved anatomical and cell architecture, restored blood vessel structure and circulatory function, restored glial inflammatory responses, spontaneous neural activity at synapses, and active cerebral metabolism over the 6-hour period compared with brains perfused with a control solution, which rapidly decomposed.
Although there was no evidence of neural activity indicating higher-order brain functions, the study raises questions about the possibility of consciousness emerging, noted Stephen Latham, JD, PhD, a Yale bioethicist who was part of the research team.
"The organized electrical activity that would be correlated with any kind of consciousness was never detected in the course of the research, and it was never a goal of the research to induce consciousness in the brains," Latham said. "It was, in fact, a concern of the researchers that consciousness might be induced, so they were prepared with anesthesia and by lowering the temperature of the brain to stop the research and cease any kind of organized electrical activity, should it occur."
There was also a neuronal activity blocker in the perfusate "because the researchers thought that brain cells might be better preserved and their functioning might be better restored if they were not active," he noted.
If consciousness were induced, "the research would have to stop until we could pull together some kind of ethics and neuro-expertise to give guidance to the future conduct of the research," Latham said. "But we have no evidence yet that that is even a possibility."
The research brings up the idea of guidelines for studies about preserving or restoring whole brains, because "animals used for such research could end up in a grey area -- not alive, but not completely dead," wrote Nita Farahany, JD, PhD, of Duke University in Durham, North Carolina, and colleagues, in an accompanying commentary. And if salvaging brains is extended to humans, debates about death and organ transplantation would emerge, added Stuart Youngner, MD, and Insoo Hyun, PhD, both of Case Western Reserve University School of Medicine in Cleveland, in another commentary published in Nature.
In the future, BrainEx could be used to test how experimental drugs affect the wiring of a large brain or help researchers study the effect of brain injury on cells and neural connections, the researchers noted.
"BrainEx's cell-protective formulations may someday find application in therapies for disorders such as stroke," Sestan said. "The isolated large mammalian brain's capacity for restoration of microcirculatory, molecular, and cellular activity has been underappreciated."
Researchers said they were able to
restore circulation and some cellular activity in pig brains hours after
death, according to their report in An artificial perfusion system known as BrainEx was able to reduce cell death and restore microcirculation and certain molecular and cellular functions in pig brains up to 4 hours postmortem, reported Nenad Sestan, MD, PhD, of Yale School of Medicine in New Haven, Connecticut, and colleagues.
The brains showed no evidence of organized, global electrical activity associated with awareness or perception, the researchers added.
"This is not a living brain, but a cellularly active brain," Sestan said in a press conference. "These findings lay the groundwork for novel approaches to studying the postmortem brain and potentially restoring the function of damaged cells within the diseased brain." Stroke treatment and recovery is perhaps the most important application of the research.
The research, supported by the NIH BRAIN Initiative, is "a real breakthrough for brain research" and had never been done before in a large, intact mammalian brain, noted Andrea Beckel-Mitchener, PhD, BRAIN Initiative Team Lead.
"It's quite a surprising result," Beckel-Mitchener said in an NIH press briefing. "We did not know that brain cells were this resilient, and under the right conditions -- such as what's been shown here with BrainEx -- that the cells could maintain some healthy function hours after loss of blood flow."
Cell death, clotting of small blood vessels, and other processes that degrade brain tissue after death have hampered researchers' ability to study a large intact postmortem brain. To overcome these limitations, Sestan and colleagues created BrainEx -- essentially, a high-tech pumping system coupled with a proprietary perfusate.
"The brain is highly sensitive to changes in oxygen levels and interruptions in blood flow," Sestan said. "However, multiple observations from our lab and others have questioned the notion that widespread cell death is unavoidable minutes, or even hours, after blood flow stops."
"For example, live cells can be harvested from postmortem brains and cultured in a dish," he continued. "This indicates that cells in the postmortem brain may still have the capacity to be revived."
In this study, the researchers placed 32 pig brains from a local pork-processing plant in the BrainEx system 4 hours after death. The brains were perfused at normal body temperature (37 degrees Celsius) for 6 hours.
BrainEx brains showed reduced cell death, preserved anatomical and cell architecture, restored blood vessel structure and circulatory function, restored glial inflammatory responses, spontaneous neural activity at synapses, and active cerebral metabolism over the 6-hour period compared with brains perfused with a control solution, which rapidly decomposed.
Although there was no evidence of neural activity indicating higher-order brain functions, the study raises questions about the possibility of consciousness emerging, noted Stephen Latham, JD, PhD, a Yale bioethicist who was part of the research team.
"The organized electrical activity that would be correlated with any kind of consciousness was never detected in the course of the research, and it was never a goal of the research to induce consciousness in the brains," Latham said. "It was, in fact, a concern of the researchers that consciousness might be induced, so they were prepared with anesthesia and by lowering the temperature of the brain to stop the research and cease any kind of organized electrical activity, should it occur."
There was also a neuronal activity blocker in the perfusate "because the researchers thought that brain cells might be better preserved and their functioning might be better restored if they were not active," he noted.
If consciousness were induced, "the research would have to stop until we could pull together some kind of ethics and neuro-expertise to give guidance to the future conduct of the research," Latham said. "But we have no evidence yet that that is even a possibility."
The research brings up the idea of guidelines for studies about preserving or restoring whole brains, because "animals used for such research could end up in a grey area -- not alive, but not completely dead," wrote Nita Farahany, JD, PhD, of Duke University in Durham, North Carolina, and colleagues, in an accompanying commentary. And if salvaging brains is extended to humans, debates about death and organ transplantation would emerge, added Stuart Youngner, MD, and Insoo Hyun, PhD, both of Case Western Reserve University School of Medicine in Cleveland, in another commentary published in Nature.
In the future, BrainEx could be used to test how experimental drugs affect the wiring of a large brain or help researchers study the effect of brain injury on cells and neural connections, the researchers noted.
"BrainEx's cell-protective formulations may someday find application in therapies for disorders such as stroke," Sestan said. "The isolated large mammalian brain's capacity for restoration of microcirculatory, molecular, and cellular activity has been underappreciated."
This work was supported by the NIH BRAIN Initiative.
The researchers disclosed findings to the Yale Office of Cooperative Research, which has filed a patent to ensure broad use of the technology. No other interests were reported.
The researchers disclosed findings to the Yale Office of Cooperative Research, which has filed a patent to ensure broad use of the technology. No other interests were reported.
last updated
Primary Source
Nature
Source Reference: Vrselja Z, et al "Restoration of brain circulation and cellular functions hours postmortem" Nature 2019, DOI: https://doi.org/10.1038/s41586-019-1099-1.Secondary Source
Nature
Source Reference: Farahany N, et al "Part-revived pig brains raise ethical quandaries" Nature 2019; 568: 299-302.Additional Source
Nature
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