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Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage.

Scott G, Hellyer PJ, Ramlackhansingh AF, Brooks DJ, Matthews PM, Sharp DJ - J Neuroinflammation (2015)

Bottom Line: Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.These findings support a link between axonal damage and persistent inflammation after brain injury.

View Article: PubMed Central - PubMed

Affiliation: Division of Brain Sciences, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London, UK.

ABSTRACT

Background: Traumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.

Findings: Using [(11)C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.

Conclusions: These findings support a link between axonal damage and persistent inflammation after brain injury.

No MeSH data available.


Related in: MedlinePlus

How chronic microglial activation and axonal injury may be linked after traumatic brain injury (TBI). Microglial activation (green cells) and traumatic axonal injury in thalamo-cortical white matter tracts (red areas) have been demonstrated after TBI. Sites of chronic microglial activation can co-localise with axonal abnormality (a) as well as along the entire axonal tract affected by injury. Remote from sites of primary axonal injury, microglia may be observed both in retrograde projection areas, towards the cell bodies of damaged neurons (b), and in anterograde areas (c and d). The thalamus is a highly connected structure. Thalamic microglial activation may be observed after TBI because of the high density of connections to damaged axons. The number of cortico-thalamic projections far exceeds thalamo-cortical projections. If microglial activation preferentially favours anterograde involvement, then relatively increased activation would be expected in the thalamus (c) compared to corresponding cortical areas (b)
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Fig3: How chronic microglial activation and axonal injury may be linked after traumatic brain injury (TBI). Microglial activation (green cells) and traumatic axonal injury in thalamo-cortical white matter tracts (red areas) have been demonstrated after TBI. Sites of chronic microglial activation can co-localise with axonal abnormality (a) as well as along the entire axonal tract affected by injury. Remote from sites of primary axonal injury, microglia may be observed both in retrograde projection areas, towards the cell bodies of damaged neurons (b), and in anterograde areas (c and d). The thalamus is a highly connected structure. Thalamic microglial activation may be observed after TBI because of the high density of connections to damaged axons. The number of cortico-thalamic projections far exceeds thalamo-cortical projections. If microglial activation preferentially favours anterograde involvement, then relatively increased activation would be expected in the thalamus (c) compared to corresponding cortical areas (b)

Mentions: Several mechanisms might underlie persistent thalamic inflammation after TBI (Fig. 3). It may be a response to focal injury. However, there was no MRI evidence of focal thalamic injury. Furthermore, there was no increase in PK binding in focal lesions [3], making a prolonged response to direct damage an unlikely explanation. Alternatively, thalamic inflammation may relate to a persistent effect of TAI. This is made more likely by the observation that activated microglia are seen at sites of TAI in acute and chronic phases [19]. The co-localisation of myelin basic protein immunoreactivity within microglia at sites of TAI suggests myelin fragments may provide a persistent trigger for inflammation [19]. The strong correlation we observed between thalamic PK binding and white matter close to the thalamus suggests a causative role for the persistent effects of TAI years after injury.Fig. 3


Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage.

Scott G, Hellyer PJ, Ramlackhansingh AF, Brooks DJ, Matthews PM, Sharp DJ - J Neuroinflammation (2015)

How chronic microglial activation and axonal injury may be linked after traumatic brain injury (TBI). Microglial activation (green cells) and traumatic axonal injury in thalamo-cortical white matter tracts (red areas) have been demonstrated after TBI. Sites of chronic microglial activation can co-localise with axonal abnormality (a) as well as along the entire axonal tract affected by injury. Remote from sites of primary axonal injury, microglia may be observed both in retrograde projection areas, towards the cell bodies of damaged neurons (b), and in anterograde areas (c and d). The thalamus is a highly connected structure. Thalamic microglial activation may be observed after TBI because of the high density of connections to damaged axons. The number of cortico-thalamic projections far exceeds thalamo-cortical projections. If microglial activation preferentially favours anterograde involvement, then relatively increased activation would be expected in the thalamus (c) compared to corresponding cortical areas (b)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4666189&req=5

Fig3: How chronic microglial activation and axonal injury may be linked after traumatic brain injury (TBI). Microglial activation (green cells) and traumatic axonal injury in thalamo-cortical white matter tracts (red areas) have been demonstrated after TBI. Sites of chronic microglial activation can co-localise with axonal abnormality (a) as well as along the entire axonal tract affected by injury. Remote from sites of primary axonal injury, microglia may be observed both in retrograde projection areas, towards the cell bodies of damaged neurons (b), and in anterograde areas (c and d). The thalamus is a highly connected structure. Thalamic microglial activation may be observed after TBI because of the high density of connections to damaged axons. The number of cortico-thalamic projections far exceeds thalamo-cortical projections. If microglial activation preferentially favours anterograde involvement, then relatively increased activation would be expected in the thalamus (c) compared to corresponding cortical areas (b)
Mentions: Several mechanisms might underlie persistent thalamic inflammation after TBI (Fig. 3). It may be a response to focal injury. However, there was no MRI evidence of focal thalamic injury. Furthermore, there was no increase in PK binding in focal lesions [3], making a prolonged response to direct damage an unlikely explanation. Alternatively, thalamic inflammation may relate to a persistent effect of TAI. This is made more likely by the observation that activated microglia are seen at sites of TAI in acute and chronic phases [19]. The co-localisation of myelin basic protein immunoreactivity within microglia at sites of TAI suggests myelin fragments may provide a persistent trigger for inflammation [19]. The strong correlation we observed between thalamic PK binding and white matter close to the thalamus suggests a causative role for the persistent effects of TAI years after injury.Fig. 3

Bottom Line: Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.These findings support a link between axonal damage and persistent inflammation after brain injury.

View Article: PubMed Central - PubMed

Affiliation: Division of Brain Sciences, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London, UK.

ABSTRACT

Background: Traumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.

Findings: Using [(11)C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.

Conclusions: These findings support a link between axonal damage and persistent inflammation after brain injury.

No MeSH data available.


Related in: MedlinePlus