Even mild traumatic brain injuries can kill brain tissue

Scientists have watched a mild traumatic brain injury play out in the living brain, prompting swelling that reduces blood flow and connections between neurons to die.

“Even with a mild trauma, we found we still have these ischemic blood vessels and, if blood flow is not returned to normal, synapses start to die,” said Dr. Sergei Kirov, neuroscientist and Director of the Human Brain Lab at the Medical College of Georgia at Georgia Regents University.

They also found that subsequent waves of depolarization – when brain cells lose their normal positive and negative charge – quickly and dramatically increase the losses.

Researchers hope the increased understanding of this secondary damage in the hours following an injury will point toward better therapy for the 1.7 million Americans annually experiencing traumatic brain injuries from falls, automobile accidents, sports, combat and the like.  While strategies can minimize impact, no true neuroprotective drugs exist, likely because of inadequate understanding about how damage unfolds after the immediate impact.

Kirov is corresponding author of a study in the journal Brain describing the use of two-photon laser scanning microscopy to provide real-time viewing of submicroscopic neurons, their branches and more at the time of impact and in the following hours.

Scientists watched as astrocytes – smaller cells that supply neurons with nutrients and help maintain normal electrical activity and blood flow – in the vicinity of the injury swelled quickly and significantly. Each neuron is surrounded by several astrocytes that ballooned up about 25 percent, smothering the neurons and connective branches they once supported.

“We saw every branch, every small wire and how it gets cut,” Kirov said. “We saw how it destroys networks. It really goes downhill. It’s the first time we know of that someone has watched this type of minor injury play out over the course of 24 hours.”

Stressed neurons ran out of energy and became silent but could still survive for hours, potentially giving physicians time to intervene, unless depolarization follows. Without sufficient oxygen and energy, internal pumps that ensure proper polarity by removing sodium and pulling potassium into neurons, can stop working and dramatically accelerate brain-cell death.

“Like the plus and minus ends of a battery, neurons must have a negative charge inside and a positive charge outside to fire,” Kirov said. Firing enables communication, including the release of chemical messengers called neurotransmitters.

“If you have six hours to save tissue when you have just lost part of your blood flow, with this spreading depolarization, you lose tissue within minutes,” he said.

While common in head trauma, spreading depolarization would not typically occur in less-traumatic injuries, like his model. His model was chemically induced to reveal more about how this collateral damage occurs and whether neurons could still be saved. Interestingly, researchers found that without the initial injury, brain cells completely recovered after re-polarization but only partially recovered in the injury model.

While very brief episodes of depolarization occur as part of the healthy firing of neurons, spreading depolarization exacerbates the initial traumatic brain injury in more than half of patients and results in poor prognosis, previous research has shown. However, a 2011 review in the journal Nature Medicine indicated that short-lived waves can actually protect surrounding brain tissue. Kirov and his colleagues wrote that more study is needed to determine when to intervene.

One of Kirov’s many next steps is exploring the controversy about whether astrocytes’ swelling in response to physical trauma is a protective response or puts the cells in destruct mode. He also wants to explore better ways to protect the brain from the growing damage that can follow even a slight head injury.

Currently, drugs such as diuretics and anti-seizure medication may be used to help reduce secondary damage of traumatic brain injury. Astrocytes can survive without neurons but the opposite is not true, Kirov said. The ratio of astrocytes to neurons is higher in humans and human astrocytes are more complex, Kirov said.

Researchers discover workings of brain’s ‘GPS system’

Just as a global posi­tion­ing sys­tem (GPS) helps find your loca­tion, the brain has an inter­nal sys­tem for help­ing deter­mine the body’s loca­tion as it moves through its surroundings.

A new study from researchers at Prince­ton Uni­ver­sity pro­vides evi­dence for how the brain per­forms this feat. The study, pub­lished in the jour­nal Nature, indi­cates that cer­tain position-tracking neu­rons — called grid cells — ramp their activ­ity up and down by work­ing together in a col­lec­tive way to deter­mine loca­tion, rather than each cell act­ing on its own as was pro­posed by a com­pet­ing theory.

Grid cells are neu­rons that become elec­tri­cally active, or “fire,” as ani­mals travel in an envi­ron­ment. First dis­cov­ered in the mid-2000s, each cell fires when the body moves to spe­cific loca­tions, for exam­ple in a room. Amaz­ingly, these loca­tions are arranged in a hexag­o­nal pat­tern like spaces on a Chi­nese checker board.

“Together, the grid cells form a rep­re­sen­ta­tion of space,” said David Tank, Princeton’s Henry L. Hill­man Pro­fes­sor in Mol­e­c­u­lar Biol­ogy and leader of the study. “Our research focused on the mech­a­nisms at work in the neural sys­tem that forms these hexag­o­nal pat­terns,” he said. The first author on the paper was grad­u­ate stu­dent Cristina Dom­nisoru, who con­ducted the exper­i­ments together with post­doc­toral researcher Amina Kinkhabwala.

Dom­nisoru mea­sured the elec­tri­cal sig­nals inside indi­vid­ual grid cells in mouse brains while the ani­mals tra­versed a computer-generated vir­tual envi­ron­ment, devel­oped pre­vi­ously in the Tank lab. The ani­mals moved on a mouse-sized tread­mill while watch­ing a video screen in a set-up that is sim­i­lar to video-game vir­tual real­ity sys­tems used by humans.

She found that the cell’s elec­tri­cal activ­ity, mea­sured as the dif­fer­ence in volt­age between the inside and out­side of the cell, started low and then ramped up, grow­ing larger as the mouse reached each point on the hexag­o­nal grid and then falling off as the mouse moved away from that point.

This ramp­ing pat­tern cor­re­sponded with a pro­posed mech­a­nism of neural com­pu­ta­tion called an attrac­tor net­work. The brain is made up of vast num­bers of neu­rons con­nected together into net­works, and the attrac­tor net­work is a the­o­ret­i­cal model of how pat­terns of con­nected neu­rons can give rise to brain activ­ity by col­lec­tively work­ing together. The attrac­tor net­work the­ory was first pro­posed 30 years ago by John Hop­field, Princeton’s Howard A. Prior Pro­fes­sor in the Life Sci­ences, Emeritus.

The team found that their mea­sure­ments of grid cell activ­ity cor­re­sponded with the attrac­tor net­work model but not a com­pet­ing the­ory, the oscil­la­tory inter­fer­ence model. This com­pet­ing the­ory pro­posed that grid cells use rhyth­mic activ­ity pat­terns, or oscil­la­tions, which can be thought of as many fast clocks tick­ing in syn­chrony, to cal­cu­late where ani­mals are located. Although the Prince­ton  researchers detected rhyth­mic activ­ity inside most neu­rons, the activ­ity pat­terns did not appear to par­tic­i­pate in posi­tion calculations.

Simple Innovation to Electrodes Makes a Big Difference

The electroencephalogram (EEG) for human uses has been around since 1924. Small metal discs placed along the scalp measure electrical activity in the human brain, important in diagnosing or evaluating epilepsy, sleep disorders and other conditions.

But these electrodes have changed little since their introduction, and are far from perfect. Among other things, they pick up extraneous noise and movement in addition to brain wave activity, often making the readings difficult to interpret.

Walt Besio thinks he has a better way.

The National Science Foundation-funded scientist, who is associate professor of biomedical engineering at the University of Rhode Island, has invented a new and improved electrode, one that produces a performance difference that he says is akin to “taking the rabbit ears you used to have for your television set, and converting to high definition.”

His innovation is relatively simple, but apparently makes a big difference. Besio added two new metal rings around the basic disc, a change that eliminates outside noises and improves spatial resolution.

"EEG has two main problems: It’s very noisy and contaminated with artifacts, and it’s spatial resolution is bad," he explains. "We have improved the signal-to-noise ratio. It’s four times better than it was before. Because it is now a very local signal, it means we can put electrodes closer together, which improves spatial resolution, meaning you can better determine where the signal is coming from."

The additional rings work almost like an inner tube tossed on top of a rippling body of water. “The water is flat in the center of the inner tube and choppy on the outside,” he says. “The outer rings on the electrodes behave like that inner tube.”

For researchers and clinicians, having improved electrodes could open up potential new uses, as well as improve current ones-more accurate epilepsy diagnosis, for example, as well as the promise of “reading” someone’s thoughts in the future, with the goal, for example, of activating an otherwise inert body part, such as an arm or leg, and ultimately helping people with spinal cord injuries.

The aim is to have the highly sensitive electrodes first translate a person’s thoughts into electrical impulses that can be read by a computer, then, eventually move to robots, and later, limbs. Other scientists are conducting similar research, but Besio wants to show “that it works better with these types of electrodes.”

Grid cell firing patterns signal environmental novelty by expansion

The hippocampal formation plays key roles in representing an animal’s location and in detecting environmental novelty to create or update those representations. However, the mechanisms behind this latter function are unclear. Here, we show that environmental novelty causes the spatial firing patterns of grid cells to expand in scale and reduce in regularity, reverting to their familiar scale as the environment becomes familiar. Simultaneously recorded place cell firing fields remapped and showed a smaller, temporary expansion. Grid expansion provides a potential mechanism for novelty signaling and may enhance the formation of new hippocampal representations, whereas the subsequent slow reduction in scale provides a potential familiarity signal.