Molecular imaging of neuroinflammation in patients after mild traumatic brain injury: a longitudinal ¹²³I‐CLINDE single photon emission computed tomography study

Abstract

Background and purpose Neuroinflammation has been proposed as part of the pathogenesis of post‐concussion symptoms (PCS), but the inflammatory response of the human brain to mild traumatic brain injury (mTBI) remains unknown. We hypothesized that a neuroinflammatory response is present in mTBI at 1–2 weeks post‐injury and persists in patients with PCS. Methods We scanned 14 patients with mTBI without signs of structural damage at 1–2 weeks and 3–4 months post‐injury and 22 healthy controls once using the single photon emission computed tomography tracer 123I‐CLINDE, which visualizes translocator protein (TSPO), a protein upregulated in active immune cells. PCS was defined as three or more persisting symptoms from the Rivermead Post Concussion Symptoms Questionnaire at 3 months post‐injury. Results Across brain regions, patients had significantly higher 123I‐CLINDE binding to TSPO than healthy controls, both at 1–2 weeks after the injury in all patients (P = 0.011) and at 3–4 months in the seven patients with PCS (P = 0.006) and in the six patients with good recovery (P = 0.018). When the nine brain regions were tested separately and results were corrected for multiple comparisons, no individual region differed significantly, but all estimated parameters indicated increased 123I‐CLINDE binding to TSPO, ranging from 2% to 19% in all patients at 1–2 weeks, 13% to 27% in patients with PCS at 3–4 months and −9% to 17% in patients with good recovery at 3–4 months. Conclusions Neuroinflammation was present in mTBI at 1–2 weeks post‐injury and persisted at 3–4 months post‐injury with a tendency to be most pronounced in patients with PCS.

The NLRP3 inflammasome in traumatic brain injury: potential as a biomarker and therapeutic target

“…There is limited clinical research on glial activation following mTBI; however, the emergence of positron emission tomography (PET) tracers that bind to the 18 kDa translocator protein (TSPO) that is associated with microglia has enabled in vivo clinical imaging of microglial activation. Eber et al found that at 1-2 weeks and 3-4 months post-mTBI, patients who had sustained an mTBI had significantly higher TSPO binding when compared to healthy controls [77]. Additionally, a preliminary study of former athletes with an extensive history of mTBI found significantly higher TSPO expression in comparison to healthy age-matched controls [78].…”

The relationship between symptom burden and systemic inflammation differs between male and female athletes following concussion

“…In addition, symptoms commonly observed following SRC have also been reported in a variety of other conditions such as polytrauma, infection, and mental illness [2][3][4][5]. In views of this, inflammation presents as a unifying concept, as it has not only been associated with concussion-like symptoms across numerous medical conditions [5], but is increasingly recognized as an important and prominent feature of concussion secondary injury [6][7][8][9][10]. Therefore, investigating the relationship between inflammation and symptom burden following concussion may help elucidate clinically meaningful pathophysiological mechanisms that mediate patient recovery [11,12].…”

Transcranial low‐frequency pulsating electromagnetic fields (T‐PEMF) as post‐concussion syndrome treatment

“…Thus, rodent studies have repeatedly demonstrated an inflammatory response following mTBI with acute and delayed activation of microglia and astrocytes and an increased cytokine production both systemically and within the brain 14 . Recently, the first study in humans using molecular imaging demonstrated neuroinflammation after mTBI was published, with findings indicating neuroinflammation of deeper brain regions 3‐4 months after mTBI, and with correlation to presence of post‐concussion symptoms 15 …”