While Wednesday’s announcement that Yale researchers restored cell function in postmortem pig brains sheds no light on the feasibility of reviving consciousness, it does suggest new opportunities for stroke treatments, disease models and validation of findings from banked brain tissues.
In a study published in Nature, a team from Yale School of Medicine showed a perfusion system delivering a cell-protective cocktail, dubbed BrainEx, preserved tissue architecture and restored cellular function and metabolism in pig brains four hours postmortem.
The cocktail contained agents that suppressed neuronal firing in the brains, and the group did not detect activity patterns indicative of cognitive function. The researchers did show in separate experiments, however, that individual neurons in these brains were capable of firing action potentials, demonstrating that at least some of their electrophysiological function had been preserved.
The results contradict the assumption that irreversible loss of brain function occurs within minutes of blood flow interruption, and suggest therapies with multipronged effects similar to the BrainEx cocktail could help recover some brain cell functions after stroke. Yale has filed a patent covering broad use of the technology.
The cocktail consisted of Hemopure, a hemoglobin-containing blood substitute from HbO2 Therapeutics LLC, spiked with sugars, antibiotics, a free radical trapping agent, a vasodilator, the anti-convulsant lamotrigine, and inhibitors of caspase activity, necroptosis and reactive oxygen species formation, as well as a detection agent.
HbO2 Therapeutics markets Hemopure in South Africa to treat adult surgical patients with anemia, and in the Russian Federation for acute anemia. The company, which did not participate in the Nature study beyond a material transfer agreement, did not return requests for comment.
The authors think the BrainEx technology could also be used to characterize drug effects. They showed the treated brains responded as expected to the antihypertensive drug nimodipine and the immunostimulant lipopolysaccharide.
The technology could also help bridge the gap between molecular studies in banked brain tissues and functional studies in live subjects, providing a platform for functional target validation through experiments gauging cell- or tissue-level activity. Researchers in search of molecular targets and biomarkers for neurological diseases have been ramping up transcriptomic studies of postmortem human brain samples (see “Molecular Mentality“).
“This platform could offer investigators the opportunity to conduct prospective, functional ex vivo studies in intact brains that would otherwise be limited to static histological, biochemical or structural investigation,” the authors wrote.
Andrea Beckel-Mitchener, team lead for the BRAIN Initiative at NIH’s National Institute of Mental Health (NIMH), said several hurdles would have to be cleared before the technology could move from animal to human brains, including optimizing the BrainEx system for human biology, and adapting donor informed consent procedures.
NIMH’s Brain Initiative co-funded the study.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.