New Tool May Transform Study of Brain Structure, Function

Researchers have developed a high-tech support system that can keep a large mammalian brain from rapidly decomposing in the hours after death, enabling study of certain molecular and cellular functions. With funding through the BRAIN Initiative, researchers developed a way to deliver an artificial blood supply to the isolated postmortem brain of a pig, preventing the degradation that would otherwise destroy many cellular and molecular functions and render it unsuitable for study. Importantly, although the researchers saw some preservation of flow through blood vessels and energy use, there was no higher level functional activity in the brain circuits. The scientific team, led by Dr. Nenad Sestan of Yale University, reported their findings Apr. 17 in the journal Nature.

“This line of research could lead to a whole new way of studying the postmortem brain,” said Dr. Andrea Beckel-Mitchener, BRAIN Initiative team lead at NIMH, which co-funded the research. “The new technology opens up opportunities to examine complex cell and circuit connections and functions that are lost when specimens are preserved in other ways. It also could stimulate research to develop interventions that promote brain recovery after loss of brain blood flow, such as during a heart attack.”

Researchers’ ability to study the functional dynamics of an intact, isolated large postmortem brain has been hampered by cell death, clotting of small blood vessels and other toxic processes that degrade the tissue following loss of blood flow and oxygen. Freezing and other preservation methods allow for only static microscopic, biochemical or structural analyses.

To overcome these limitations, Sestan and colleagues created a system called BrainEx (after “ex vivo”), specially designed to attenuate some of the processes responsible for degradation of tissue in postmortem brains. The researchers used brains from a pork processing plant that would have otherwise been discarded. The system involves pumping a solution called BEx perfusate—a proprietary mixture of protective, stabilizing and contrast agents that act as substitutes for blood—into the isolated brain’s main arteries at normal body temperature.

Brains processed with BEx 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, compared to brains perfused with a control solution, which rapidly decomposed. Importantly, there was no global electrical activity that would indicate higher-order functions, such as awareness or perception.

The results suggest that delivering protective agents to the brain through its dense network of blood vessels may hold potential for improving survival and reducing neurological deficits after trauma.