Widespread and Prolonged Increase in (<i>R</i>)-<sup>11</sup>C-PK11195 Binding After Traumatic Brain Injury

Folkersma, Hedy; Boellaard, Ronald; Yaqub, Maqsood; Kloet, Reina W.; Windhorst, Albert D.; Lammertsma, Adriaan A.; Vandertop, W. Peter; Berckel, Bart N.M. van

doi:10.2967/jnumed.110.084061

Cited by 71 publications

(59 citation statements)

References 20 publications

(20 reference statements)

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“…It is hypothesized that this microglial activation could induce a pro-inflammatory environment in the undamaged cerebral parenchyma. The findings are consistent with previous imaging PET studies, performed in living patients with the radiotracer 11 C-PK11195 [21,22].…”

Section: Discussionsupporting

confidence: 92%

“…Very interestingly, these studies showed that microglial activation remains active several months after the time of injury and, more importantly, showed a widespread distribution of microglial activation throughout the brain [21,22]. The hypothesis that a focal TBI could induce global changes in encephalic microglia has not been sufficiently explored in humans.…”

Section: Introductionmentioning

confidence: 99%

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Widespread microglial activation in patients deceased from traumatic brain injury

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Widespread microglial activation in patients deceased from traumatic brain injury

et al. 2015

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“…Excess TNF is centrally involved in the pathophysiology of chronic brain dysfunction in multiple disease states: (a) cerebral malaria; (b) TBI; (c) stroke; (d) Alzheimer’s disease; (e) frontotemporal dementia; (f) post-surgery; (g) hepatic encephalopathy Rationale: Etanercept reduces cognitive impairment in disorders associated with excess TNFClark 1989, 1991 [51, 181]Goodman 1990 [52]Perry 2001 [53]Tarkowski 2003 [223]Sjogren 2004 [54]Tweedie 2007 [55]Kaushal 2008 [86]John 2008 [56]Clark 2010, 2012 [32, 33]Chio 2010 [45]Terrando 2010 [57]Frankola 2011 [59]Butterworth 2011 [58]Clark 2012 [34]Chastre 2012 [213]Cheong 2013 [60]Chio 2013 [61]Miller 2013 [62]Etanercept reduces TNF-mediated cognitive impairment in Alzheimer’s disease, other dementias, stroke, TBI, rheumatoid arthritis, sarcoidosis, hepatic encephalopathy, post status epilepticusTobinick 2006–2012 [10, 35, 68, 69, 146, 216, 218, 219]; Griffin 2008 [217]Shi (infliximab) 2011, 2011 [195, 196]Tobinick 2008 [204, 219]Tobinick 2011–12 [4, 5] Chio 2010 [45]Tobinick 2012 [5]Chen 2010 [206]Efferich 2010 [205]Bassi 2010 [207]Butterworth 2013 [67]Tobinick 2014 [11] 4. Stroke and TBI cause chronic intracerebral glial activation and neuroinflammation Rationale: Etanercept reduces glial activation and pathologic TNF concentrationDubois 1988 [131]Myers 1991 [132]Pappata 2000 [133]Gentleman 2004 [134]Gerhard 2005 [135]Price 2006 [136]Kaushal 2008 [86]Folkersma 2011 [137]Ramlackhansingh 2011 [138]Johnson 2013 [139]Etanercept inhibits glial activation and neuroinflammationMarchand 2009 [64]…”

Section: The Nine Criteria Of Hillmentioning

confidence: 99%

“…In 2011, Folkersma et al [137], studied microglial activation in patients with moderate and severe TBI using (R)-[ 11 C]-PK11195 brain PET, 6 months after trauma. In both whole-brain and regional analysis, increased (R)-[ 11 C]-PK11195 binding potential was found compared with age- and sex-matched healthy controls.…”

Section: The Nine Criteria Of Hillmentioning

confidence: 99%

Perispinal Etanercept for Post-Stroke Neurological and Cognitive Dysfunction: Scientific Rationale and Current Evidence

Ignatowski

Spengler²,

Dhandapani

et al. 2014

CNS Drugs

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There is increasing recognition of the involvement of the immune signaling molecule, tumor necrosis factor (TNF), in the pathophysiology of stroke and chronic brain dysfunction. TNF plays an important role both in modulating synaptic function and in the pathogenesis of neuropathic pain. Etanercept is a recombinant therapeutic that neutralizes pathologic levels of TNF. Brain imaging has demonstrated chronic intracerebral microglial activation and neuroinflammation following stroke and other forms of acute brain injury. Activated microglia release TNF, which mediates neurotoxicity in the stroke penumbra. Recent observational studies have reported rapid and sustained improvement in chronic post-stroke neurological and cognitive dysfunction following perispinal administration of etanercept. The biological plausibility of these results is supported by independent evidence demonstrating reduction in cognitive dysfunction, neuropathic pain, and microglial activation following the use of etanercept, as well as multiple studies reporting improvement in stroke outcome and cognitive impairment following therapeutic strategies designed to inhibit TNF. The causal association between etanercept treatment and reduction in post-stroke disability satisfy all of the Bradford Hill Criteria: strength of the association; consistency; specificity; temporality; biological gradient; biological plausibility; coherence; experimental evidence; and analogy. Recognition that chronic microglial activation and pathologic TNF concentration are targets that may be therapeutically addressed for years following stroke and other forms of acute brain injury provides an exciting new direction for research and treatment.

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“…227 Two recent reports of studies use the radiopharmaceutical [ 11 C]PK11195, a marker for neuroinflammation that reflects microglial activation and increased macrophages. 228,229 These studies demonstrated ongoing neuroinflammation that was widespread in the brain, yet more prominent in deeper brain structures. This neuroinflammation was present as late as 17 years post-TBI.…”

Section: Chronic Tbimentioning

confidence: 98%

A Review of the Effectiveness of Neuroimaging Modalities for the Detection of Traumatic Brain Injury

Amyot

Arciniegas

et al. 2015

Journal of Neurotrauma

169

147

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The incidence of traumatic brain injury (TBI) in the United States was 3.5 million cases in 2009, according to the Centers for Disease Control and Prevention. It is a contributing factor in 30.5% of injury-related deaths among civilians. Additionally, since 2000, more than 260,000 service members were diagnosed with TBI, with the vast majority classified as mild or concussive (76%). The objective assessment of TBI via imaging is a critical research gap, both in the military and civilian communities. In 2011, the Department of Defense (DoD) prepared a congressional report summarizing the effectiveness of seven neuroimaging modalities (computed tomography [CT], magnetic resonance imaging [MRI], transcranial Doppler [TCD], positron emission tomography, single photon emission computed tomography, electrophysiologic techniques [magnetoencephalography and electroencephalography], and functional near-infrared spectroscopy) to assess the spectrum of TBI from concussion to coma. For this report, neuroimaging experts identified the most relevant peer-reviewed publications and assessed the quality of the literature for each of these imaging technique in the clinical and research settings. Although CT, MRI, and TCD were determined to be the most useful modalities in the clinical setting, no single imaging modality proved sufficient for all patients due to the heterogeneity of TBI. All imaging modalities reviewed demonstrated the potential to emerge as part of future clinical care. This paper describes and updates the results of the DoD report and also expands on the use of angiography in patients with TBI.

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Widespread and Prolonged Increase in (R)-¹¹C-PK11195 Binding After Traumatic Brain Injury

Cited by 71 publications

References 20 publications

Widespread microglial activation in patients deceased from traumatic brain injury

Widespread microglial activation in patients deceased from traumatic brain injury

Perispinal Etanercept for Post-Stroke Neurological and Cognitive Dysfunction: Scientific Rationale and Current Evidence

A Review of the Effectiveness of Neuroimaging Modalities for the Detection of Traumatic Brain Injury

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Widespread and Prolonged Increase in (R)-11C-PK11195 Binding After Traumatic Brain Injury

Cited by 71 publications

References 20 publications

Widespread microglial activation in patients deceased from traumatic brain injury

Widespread microglial activation in patients deceased from traumatic brain injury

Perispinal Etanercept for Post-Stroke Neurological and Cognitive Dysfunction: Scientific Rationale and Current Evidence

A Review of the Effectiveness of Neuroimaging Modalities for the Detection of Traumatic Brain Injury

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Widespread and Prolonged Increase in (R)-¹¹C-PK11195 Binding After Traumatic Brain Injury