Use of Photobiomodulation to Mitigate Oxidative Stress, Neuroinflammation, and Behavioral Deficits after Traumatic Brain Injury

1. Use of Photobiomodulation (PBM) to
Mitigate Oxidative Stress,
Neuroinflammation, and Behavioral
Deficits after Traumatic Brain Injury (TBI)
Julia Malewicz
Mentors:
Dr. Alana Conti - Dept. Of Psychiatry & Behavioral Neurosciences
Dr. Bruce Berkowitz - Dept. Of Ophthalmology, Visual & Anatomical
Sciences

2. Abstract
Of the nearly 3 million people annually affected by traumatic brain injuries (TBIs), more than 50%
experience persistent pain following injury and are more likelyto receive opioids for pain
management. The underlying mechanisms for this pain remain unclear. Research has shown that TBI
acutely increases reactive oxygen species (ROS) generation leading to long-term increases in
neuroinflammation, which triggers a downstream cascade that results in behavioral and functional
deficits, including pain. Because TBI patients experience pain, they are 5x more likelyto be
prescribed opioids. Opioids increase the risk of overdose, suicide, and have a potential addictive
affect. An alternative to opioids is the non-toxic and non-invasive treatment, photobiomodulation
(PBM), which is known to impact oxidative stress and inflammatory cascades. The purpose of the
current study is to examine the use of PBM to mitigate oxidative stress, neuroinflammation, and
behavioral deficits following TBI in a mouse model. An enzyme-linked immunosorbent assay
(ELISA) will be used to measure the protein levels of IL-1, a pro-inflammatory cytokine. Preliminary
research has shown positive results in the cortex region of the brain, with reduced ROS and IL-
1 levels following PBM treatment in TBI mice. The goal of this project is to examine known pain
regions in the brain and see if TBI increases neuroinflammatory markers and if PBM is a viable
alternative to opioids to reduce this, in the treatment and management of pain.

3. • Traumatic Brain Injuries (TBI) affect nearly 3
million people annually
• TBI is often associated with pain, affective
disorders, anxiety, problems focusing and
sleeping, and other psychological factors
• To date, no traditional approaches have yielded
effective interventions for TBI
What Is TBI?

4. Biochemical Effects of TBI
• TBI acutely increases reactive
oxygen species (ROS) generation
leading to long-term increases
in neuroinflammation
• Triggers downstream cascade that
results in many functional deficits,
including pain
FunctionalDeficits

5. Pain In TBI
• 70-80% of TBI patients experience pain
• 5x more likely to receive opioid-based
treatment
• Opioid use increases risk of
• Overdose, suicide, mental distress
• Vulnerability to addiction
• Sensitivity to pain
Solution: Find a non-toxic and non-invasive
alternative to opioids

6. Photobiomodulation (PBM)
As a Potential Therapeutic Agent In TBI Treatment
• PBM is non-toxicand non-invasive
• PBM uses red and near infrared (NIR) light
to trigger a downstreameffect
• Reduces oxidativestress and
inflammation in models of wound
healing and stroke, with only a few studies
suggesting a role for PBM in
improving outcomes after
severe brain injury
Red and NIR light (600-940 nm) are primarily
absorbed by cytochrome C oxidase
Mechanism of PBM

7. Preliminary PBM Data
•Preliminary from our lab indicates that PBM reduces pain sensitivity and
attenuates the inflammatory response caused by TBI in the cortex

8. Timecourse Experimental Design
• Due to COVID-19 unable to run PBM study, however I was able to run a timecourse study to
measure levels of IL-1β production in different brain regions
• Two groups of mice; sham and TBI
• TBI mice underwent 2mm impact over midline suture and sham underwent surgery with no injury
• Sacrificed after 24 hours, 7 days, and 14 days, brain punches were taken from addictionand pain
centers:
• Prefrontal cortex (PFC), anterior cingulate cortex (ACC), and dorsal hippocampus (dHC)
• Samples analyzed using enzyme-linked immunosorbent assay (ELISA)

9. ELISA Expected Results
• ELISA is used to measure protein levels
of IL-1β, a pro-inflammatory cytokine
• Following TBI we expect an increase in IL-1β
• Want to know in what brain regions and at
what timepoints does IL-1β proliferate

10. Timecourse Study Results
TBI elevated levels of the pro-inflammatory cytokine IL-1b 24 hours, 7 days, and 14 days post-injury
(n=3-5/group). p < 0.05, compared to sham controls (*).

11. Discussion
• No significant increase in IL-1β 24 hours post-injury
• Significant increase 7 days post-injury in all regions
• Unique differences between brain regions:
• ACC showed a significant increase in IL-1β 7 days post-TBI, but not 14 days
• PFC and dHC significant increase in 7 and 14 day timepoints

12. Conclusion
• IL-1β levels significantly increased during later timepoints
• Brain regions studied would be good to test effectiveness of
PBM
• Based off timecourse results, I hypothesize that mice treated
sooner with PBM following injury will show lower levels of
IL-1β vs mice that receive PBM treatment at later timepoints
• Next step is to explore PBM use in regions associated with
pain
• See whether PBM has effects in regions other than
the cortex

13. Acknowledgements
• Barber Support
• Dr. Alana Conti, Ph.D.
• Dr. Bruce Berkowitz
• Berkowitz Lab
• Dr. Kelly Bosse, Ph.D.
• Dr. Veronica Piggot, Ph.D.
• Dr. Christopher Kelly, Ph.D.