New Research: Changing metal levels in traumatic brain injury

It’s been a while since we’ve been active here, but as annual money-begging season has drawn to a close, it’s time to update everyone on the slew of new papers coming from our lab. Over the next few weeks, there’ll be a bunch more posts on the exciting developments happening in the ferrumblogger world.

To start, we’re going to look at a new paper, written by Florey PhD student Stuart Portbury, who’s been looking at how the brain responds to traumatic brain injury, or TBI. TBI is a hot topic right now, from the dangers of multiple concussions experienced by American NFL players (and the controversy regarding the recent pull-out by the NFL for a multi-million dollar project to study it’s effects in living patients) to people who like to get into locked cages and punch each other in the head (hey, consenting adults and all that…). And perhaps the biggest elephant in the room are the effects of traumatic brain injuries in the multiple sites of conflict currently tak17143ing place around the world.

What causes the long-lasting effects of concussions are still a matter of much contention, so it’s important for us to know what’s going on at the chemical level in precisely controlled conditions to better understand both how the brain responds, and what can be done to prevent it. Click through to read about thr work from Stuart and his supervisor, Associate Professor Paul Adlard, who runs the Synaptic Neurobiology Laboratory at the Florey. (Picture used from the US National Library of Medicine).

Stuart’s paper was just published in Metallomics (where you can access it free of charge here), and looked at how a controlled cortical impact influences changing metal levels up to 28 days after the initial injury. Using a specially designed instrument that delivers a controlled brain injury through an impact (see the details here, but maybe try not to think about it too much if you’re a bit squeamish), Stuart then removed the brains of mice who received the injury at 1, 3, 7, 14 and 28 days, and scanned the brains using our well-established laser ablation-inductively coupled plasma-mass spectrometry imaging technique. We took the resulting images and divided them into three separate regions radiating out from the injury site, and examined how iron, copper and zinc changes in these areas in the time following injury.

Figure 1.png

By measuring the precise levels of metals in these brain regions, Stuart could look at how metals move in and out of the injury site. Knowing that metals like iron are incredibly important in the inflammatory response to injury, but, as a side effect, can release a huge amount of potentially reactive and dangerous iron, we hypothesised that in the time following the injury there would be long-lasting evidence of metal retention at the injury site, and that’s exactly what we saw:

TBI Figure v2.jpg

Now, aside from the fact a chunk of brain seems to be missing, which would be a red flag for anyone, it’s particularly interesting to note how things got worse over time. Without boring you with a whole bunch of bar graphs and statistical tests, what we can summarise is this:

  • Iron levels in the damaged regions increased after the injury, and continued to accumulate up to and including the 28-day period.
  • Ditto for copper and zinc. For copper, this can be a particular concern, as it’s potential to do chemical damage is much greater than iron, which is one of the reasons that you’ll generally find a lesser amount of this metal in the brain.
  • The changes weren’t huge for all metals, which introduces a bit of a conundrum. Metals going up generally isn’t a good thing, though when it’s happening at low levels, it’s hard for us to say that metals alone are the ‘smoking gun’ that identifies why traumatic brain injury.

This last point is now the direction Stuart is going in. Finding out what else is going on in these brains and identifying how they’re related to metal levels is the key in finding new ways we can try to mitigate the damage caused by TBI. Keep watch here for more updates on Stuart’s fascinating work in the future.

Posted in Freshly forged: New research from our lab

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