‘Resetting’ immune cells may improve recovery in mice following TBI, even months after injury

Written by Sharon Salt, Senior Editor

A recent study in the Journal of Neuroscience has indicated that targeting overactive immune cells and dampening their neurotoxic effects may offer new therapeutic strategies for traumatic brain injury (TBI).

Once a TBI occurs, microglia morph into an inflammatory state to help protect the brain. However, long-term inflammation may contribute towards neurological degeneration after a TBI.

Within this pre-clinical study, the researchers examined the effects of delayed depletion of chronically activated microglia on functional recovery and neurodegeneration up to 3 months post-injury in mice. The team reported that at 1-month post-injury, they were able to inhibit a receptor that is required for microglia to survive (CSF1R). The CSF1R inhibitor was then withdrawn 1-week post-administration to allow for microglial repopulation.

According to the investigators, this inhibition killed 95% of the microglial cells in mice. However, once the inhibition ended, the cells were able to bounce back to normal levels.

When the inhibition was stopped after 1 week, the researchers found that this ‘reset’ the mice’s microglia – that is, the new cells were in a less inflammatory state. The mice made a better recover than those that didn’t receive treatment, exhibiting less brain damage, fewer neuron death and better motor and cognitive performance.

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“These preclinical studies suggest that the consequences of TBI on brain degeneration and related neurological impairment may be modifiable quite a long time after injury by targeting inflammation pathways, which is a finding at odds with widely accepted views about head injury,” commented study author, David Loane (Trinity College Dublin, Ireland).

Loane concluded that: “The exciting thing is the possibility that we may one day be able to minimize brain degeneration and neurological impairment in people who have suffered a TBI. It will of course always be incredible important to act quickly whenever someone suffers a TBI, but our findings suggest targeting inflammation pathways further down the treatment line may make a major difference to long-term brain health and recovery.”

Sources: Henry RJ, Ritzel RM, Barrett JP et al. Microglial depletion with CSF1R inhibitor during chronic phase of experimental traumatic brain injury reduces neurodegeneration and neurological deficits. J. Neurosci. doi:10.1523/JNEUROSCI.2402-19.2020 (2020) (Epub ahead of print); www.eurekalert.org/emb_releases/2020-02/tcd-ic022120.php