Abstract
Traumatic brain injury triggers neuroinflammation that may contribute to progressive neurodegeneration. We investigated patterns of recruitment of astrocytes and microglia to inflammation after brain trauma by firstly characterising expression profiles over time of marker genes following TBI, and secondly by monitoring glial morphologies reflecting inflammatory responses in a rat model of traumatic brain injury (i.e. the lateral fluid percussion injury). Gene expression profiles revealed early elevation of expression of astrocytic marker glial fibrillary acidic protein relative to microglial marker allograft inflammatory factor 1 (also known as ionized calcium-binding adapter molecule 1). Adult rat brains collected at day 7 after injury were processed for immunohistochemistry with allograft inflammatory factor 1, glial fibrillary acidic protein and complement C3 (marker of bad/disruptive astrocytic A1 phenotype). Astrocytes positive for glial fibrillary acidic protein and complement C3 were significant increased in the injured cortex and displayed more complex patterns of arbourisation with significantly increased bifurcations. Our observations suggested that traumatic brain injury changed the phenotype of microglia from a ramified appearance with long, thin, highly branched processes to a swollen amoeboid shape in the injured cortex. These findings suggest differential glial activation with astrocytes likely undergoing strategic changes in morphology and function. Whilst a detailed analysis is needed of temporal patterns of glial activation, ours is the first evidence of a role for the bad/disruptive astrocytic A1 phenotype in an open head model of traumatic brain injury.
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Abbreviations
- A1:
-
Neurotoxic phenotype of reactive astrocytes
- A2:
-
Neuroprotective phenotype of reactive astrocytes
- Aif1:
-
Allograft inflammatory factor 1
- AuD:
-
Auditory cortex
- BBB:
-
Blood–brain barrier
- BDNF:
-
Brain-derived neurotrophic factor
- C3:
-
Complement component 3
- C3+:
-
Complement component 3 immunoreactive positive
- CCI:
-
Controlled cortical impact injury
- CNS:
-
Central nervous system
- CSPG:
-
Chondroitin sulphate proteoglycan
- C1q:
-
Complement component 1q
- CD68:
-
Cluster of differentiation 68
- CSF-1:
-
Colony stimulating factor 1
- DAMPs:
-
Damage-associated molecular patterns
- DAM:
-
Disease-associated microglia
- DAPI:
-
4′-6-diamidino-2-phenylindole
- FPI:
-
Lateral fluid percussion injury
- GFAP:
-
Glial fibrillary acidic protein
- GFAP+:
-
Glial fibrillary acidic protein immunoreactive positive
- HCl:
-
Hydrochloric acid
- Iba1:
-
Ionized calcium-binding adapter molecule 1
- IL:
-
Interleukin
- M1:
-
Neurotoxic phenotype of reactive microglia
- M2:
-
Neuroprotective phenotype of reactive microglia
- NDS:
-
Normal donkey serum
- PBS:
-
Phosphate buffered saline
- S2:
-
Region somatosensory cortex
- Sham:
-
Sham-injury
- TBI:
-
Traumatic brain injury
- TGF-β:
-
Transforming growth factor beta 1
- TNF:
-
Tumor necrosis factor
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Acknowledgements
PMB is pleased to contribute a paper to this Special Issue honouring Tony Turner who has been a colleague furthering the neurochemical cause via the Journal of Neurochemistry and internationally (ISN) and in Europe (ESN) for some 20 years. This work is partly funded by the J and M Nolan Family Trust. This work was supported by the Victorian Government through the Operational Infrastructure Scheme.
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Special issue in honor of Prof. Anthony J. Turner.
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Clark, D.P.Q., Perreau, V.M., Shultz, S.R. et al. Inflammation in Traumatic Brain Injury: Roles for Toxic A1 Astrocytes and Microglial–Astrocytic Crosstalk. Neurochem Res 44, 1410–1424 (2019). https://doi.org/10.1007/s11064-019-02721-8
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DOI: https://doi.org/10.1007/s11064-019-02721-8