Appearance of Cxcl10-expressing cell clusters is common for traumatic brain injury and neurodegenerative disorders.
Traumatic brain injury (TBI) in the mouse results in the rapid appearance of scattered clusters of cells expressing the chemokine Cxcl10 in cortical and subcortical areas. To extend the observation of this unique pattern, we used neuropathological mouse models using quantitative reverse transcriptase-polymerase chain reaction, gene array analysis, in-situ hybridization and flow cytometry. As for TBI, cell clusters of 150-200 mum expressing Cxcl10 characterize the cerebral cortex of mice carrying a transgene encoding the Swedish mutation of amyloid precursor protein, a model of amyloid Alzheimer pathology. The same pattern was found in experimental autoimmune encephalomyelitis in mice modelling multiple sclerosis. In contrast, mice carrying a SOD1(G93A) mutant mimicking amyotrophic lateral sclerosis pathology lacked such cell clusters in the cerebral cortex, whereas clusters appeared in the brainstem and spinal cord. Mice homozygous for a null mutation of the Cxcl10 gene did not show detectable levels of Cxcl10 transcript after TBI, confirming the quantitative reverse transcriptase-polymerase chain reaction and in-situ hybridization signals. Moreover, unbiased microarray expression analysis showed that Cxcl10 was among 112 transcripts in the neocortex upregulated at least threefold in both TBI and ageing TgSwe mice, many of them involved in inflammation. The identity of the Cxcl10(+) cells remains unclear but flow cytometry showed increased numbers of activated microglia/macrophages as well as myeloid dendritic cells in the TBI and experimental autoimmune encephalomyelitis models. It is concluded that the Cxcl10(+) cells appear in the inflamed central nervous system and may represent a novel population of cells that it may be possible to target pharmacologically in a broad range of neurodegenerative conditions.
Israelsson
Charlotte
C
Department of Neuroscience, Developmental Neuroscience, Biomedical Center, Uppsala University, PO Box 593, SE-751 24 Uppsala, Sweden.
Bengtsson
Henrik
H
Lobell
Anna
A
Nilsson
Lars N G
LN
Kylberg
Annika
A
Isaksson
Magnus
M
Wootz
Hanna
H
Lannfelt
Lars
L
Kullander
Klas
K
Hillered
Lars
L
Ebendal
Ted
T
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D002469:Cell Separation; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054357:Chemokine CXCL10