Table 2.

Evidence for disseminated brain inflammation in patients with traumatic brain injury

Study design	Patients inclusion (n)	Control group (n)	Age	Approaches	Disease phase during detection	Findings
Cross-sectional29	Moderate to severe TBIa (10)	Healthy controls (22)	36-55	PK11195-PET	11 months to 17 years after injury	Significantly higher PK11195 binding was observed in the thalamus, putamen, occipital cortices, and posterior limb of the internal capsules of survivors of TBI, without hemispheric differences.
Prospective30	Moderate to severe TBIb (8)	Healthy controls (7)	18-63	PK11195-PET	6 months after injury	PK11195 binding was significantly increased throughout the brains of patients with TBI.
Cross-sectional28	Patients with TBI who survived for different times (52)	Uninjured, no documented history of TBI, Alzheimer’s disease or Down syndrome (44)	9-89	Autopsy and immunohisto-chemistry	10 h to 47 years after injury	Acute phase (< 2 weeks): no obvious change compared with controls; sub-acute phase (2 weeks–1 year): focal clusters of activated microglia; long-term phase (>1 year): activated microglia were distributed throughout the corpus callosum.
Cross-sectional31	Former American football players (11)	Healthy controls (9)	65 ± 5	DPA-713-PET	24–42 years since last playing	DPA-713 binding was significantly increased throughout the brains of retired players.
Cross-sectional32	Active and former American football players (14)	Healthy controls (15)	31 ± 6	DPA-713-PET	7 ± 6.4 years after last self-reported concussion	Players showed higher total distribution volumes.

(n) indicates the sample size. PK11195 and DPA-713 are ¹¹C-labeled translocator protein (TSPO) ligands used for PET imaging of brain inflammation. TSPO is expressed at high levels in activated microglia, it is also expressed in peripheral monocytes and, to a lesser extent, astrocytes. Therefore, the information about inflammation delivered by this signal may be mediated by multiple cells

PET positron emission tomography, TBI traumatic brain injury

^aDefined based on the Mayo classification of patients who meet one or more following criteria: (1) death due to this TBI; (2) loss of consciousness of 30 minutes or more; (3) post-traumatic anterograde amnesia for at least 24 h; (4) worst Glasgow Coma Scale full score recorded in the first 24 h <13; and (5) the presence of one or more of the following symptoms: intracerebral hematoma, subdural hematoma, epidural hematoma, cerebral contusion, hemorrhagic contusion, penetrating TBI (dura penetrated), subarachnoid hemorrhage, or brain stem Injury

^bDefined according to the score on the Glasgow Coma Scale, 9–13 points represents a moderate injury and ≤ 8 points represents a severe injury