How brain cells die after concussive trauma

After a blow to the head, how long before your brain cells die? A few seconds – maybe minutes?

A new study shows the timeframe is more like a few hours – and snapped images of the different types of damage the cells suffered, depending on the trauma.

Researchers from Brown University in the US built a device that squashes rat neurons embedded in a 3-D collagen frame and takes photos of the cells in real time with a powerful microscope. 

They saw signs of irreparable structural damage to the neurons within six hours in some cases – perhaps enough time, the write, to intervene with cell-healing drugs. The work was published in Scientific Reports.

While you might develop a bit of a headache immediately after tripping and cracking your head on the floor, researchers have known for a while that most brain cell damage and death doesn’t happen right away.

Most studies into neuron death has been done in 2-D, on slides or petri dishes.

After shearing or stretching, the cell’s cytoskeleton – a network of structural proteins that provide shape and support – is left twisted and deformed. Sometimes a cell can straighten it out again, but if the damage is bad enough, the cell kills itself hours or days afterwards.

Such 2-D studies, though, don’t measure the effects of compression – such as the brain squashing against the inside of the skull during a head-on rugby or football tackle. For that, you need to add an extra dimension.

So Christian Franck, a mechanical engineer at Brown interested in biomechanics, and his team built a device that could measure compressive forces on brain cells in 3-D.

Rat brain cells grew in a collagen matrix. Then a hydraulic piston crushed the neuron-filled collagen blob and a microscope snapped pictures of the cells. 

In particular, they were interested in some of the main signs of cell death such as the retraction of a cell’s long arm-like projections called axons and “blebbing”, where the cell detaches its cytoskeleton from its membrane, causing it to swell in parts.

Franck and his crew saw these danger signs within a few hours after compression.

The timing of cell death varied according to the severity of compression. A cell that bore a 7% strain died in around 12 hours while a cell suffering a 12% strain died in seven hours.

Fatima Nasrallah, a neuroscientist at the Queensland Brain Institute in Australia, says the technique could help determine how neuroprotective agents – such as omega-3 oils – affect the progression of injuries in the brain.

“If you give the cells [in the collagen] something you think might be neuroprotective, you could see how they react after trauma to give you more of an understanding that it might help the cells from degenerating,” she says.

“We might get to the point where we can come with up a range of agents that [an athlete] might take pre-season, or for a long period of time, so they know if they do get a concussion it might lessen the impact of that injury on their brain.”

But, she adds, a couple of cells embedded in collagen can’t reflect the nature of a full brain: its rich range of structures and cell types, including immune cells called microglia that swoop in on brain injuries and help mop up damage.

Franck agrees: “Our system doesn’t have nearly the complexity of a real brain, so we’re not saying that it plays out exactly this way in [traumatic brain injury] patients.

“But we wanted to start simply and get fundamental data on how neurons respond to these strains. We think it provides a good starting point for further research.”