A Novel Pharmacological Approach to Traumatic Brain Injury Care
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A series of MRI scans of a person’s brain (temet/iStock)
Have you ever experienced a concussion? If so, you might remember days spent in dark, quiet rooms slowly passing the time as your brain and body recover from inflammation, dizziness, intense light and sound sensitivity, and even amnesia. I can recall my own car accident-induced traumatic brain injury (TBI) and the absolutely draining symptoms and recovery that followed: nausea, impaired motor skills, brain fog, and light and sound sensitivity that lingers to this day. Recovery can last as short as a month for a mild concussion, to a lifetime for a more severe TBI, although the bulk of progress takes place within the first year. Recovery is a gentle process aided by ample rest, patience, and anti-nausea and pain medications. Currently, surgery and time are the best antidotes to control detrimental brain bleeding and neuroinflammation. Notably absent are pharmacological treatment options for TBI recovery. Fortunately, a recent paper by Lecca and colleagues proposes a novel drug that targets neuroinflammation and may radically change the healing landscape for TBIs.
The compound behind this drug is tetrafluorobornylphthalimide (TFBP). TFBP derives from the same class as thalidomide, a well-known teratogenic drug that was heavily marketed to treat morning sickness in pregnant women throughout the 1950’s and 60’s. It’s also the unfortunate culprit of the thalidomide tragedy that resulted in numerous babies born with a range of disabilities (e.g., brain damage, facial disfigurement, shortening/absence of limbs). Despite its teratogenic nature, thalidomide is a powerful anti-inflammatory agent that has been used for years in diseases such as myeloma and Hansen’s disease. By changing the ring structure in thalidomide to create TFBP the researchers were able to eliminate the teratogenic properties while retaining the anti-inflammatory properties.
To test TFBP as a potential treatment for neuroinflammation associated with TBI, the researchers in this study used the controlled cortical impact model to induce TBI in mice. In this model a small tool repeatedly impacts a mouse’s cortical surface to induce neuroinflammation. Administering TFBP 1 and 24 hours post-injury significantly reduced pro-inflammatory cytokines like TNF-α, IFN-γ and IL-5 for four hours in the plasma and cerebral cortex compared to controls. Under normal conditions, cytokines trigger and mobilize our immune system’s response to fight against foreign pathogens, and in turn, cause local inflammation. However, following severe injury, the inflammation can become excessive and cause the body more stress and tissue damage. Thus, reduced levels of these compounds prevents the inflammation-induced synaptic and neuronal dysfunction and death and allows the body to focus more energy on healing. TFBP treated mice also showed reduced motor skill deficits and significantly reduced cortical lesion volume one week post-injury when compared to control mice, indicative of enhanced recovery from a number of common TBI symptoms. To examine the developmental impact of TFBP on embryonic cells, the researchers administered 100 L aliquots of TFBP on the surfaces of chicken embryos and monitored their development. They found the embryos grew morphologically normal and showed no adverse effects, suggesting that TFBP may be a safe treatment for TBI patients who are pregnant.
Overall, TFBP appears to represent a new class of thalidomide drugs that may be the key to reducing the neuroinflammation and behavioral deficits associated with TBI. And unlike previous treatments, it’s safe to use during pregnancy. The promising results of this study warrant further investigation into TFBP as a treatment for TBI and other neurological disorders with excessive inflammatory elements.
Jane Arterberry is working on her undergraduate degree in biology with a chemistry minor at Portland State University Honors College. She is a member of PSU’s eXtreme Virus Lab, a BUILD EXITO trainee, and interested in genetics and molecular biology. Her favorite things include watching live music, petting everyone’s dogs, and making academia a more inclusive place.
