Upregulation of CSPG3 Accompanies Neuronal Progenitor Proliferation and Migration in EAE

Sajad, Mir; Zargan, Jamil; Chawla, Raman; Umar, Sadiq; Khan, Haider Ali

doi:10.1007/s12031-010-9476-0

Cited by 17 publications

(12 citation statements)

References 47 publications

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“…Increased neurocan expression is consistent with other reports showing induction of neurocan levels following different types of insults to the mammalian central nervous system, including a knife wound injury to the cortex (Asher et al, 2000;Asher et al, 2002), a contusion injury to the spinal cord (Andrews et al, 2012;Massey et al, 2008) as well as inflammatory insults (Sajad et al, 2011) and chronic glial scars (McKeon et al, 1999). In cell culture, neurocan is anti-adhesive and can effectively repel axons, and these actions were effectively abrogated after treatment of neurocan with chondroitinase ABC, supporting a primary role of GAG chains in actions of neurocan (Friedlander et al, 1994).…”

Section: Discussionsupporting

confidence: 92%

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Katagiri

Susarla

et al. 2012

J of Comparative Neurology

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Chondroitin sulfate proteoglycans (CSPGs) play a pivotal role in many neuronal growth mechanisms including axon guidance and the modulation of repair processes following injury to the spinal cord or brain. Many actions of CSPGs in the central nervous system (CNS) are governed by the specific sulfation pattern on the glycosaminoglycan (GAG) chains attached to CSPG core proteins. To elucidate the role of CSPGs and sulfated GAG chains following traumatic brain injury (TBI), controlled cortical impact injury of mild to moderate severity was performed over the left sensory motor cortex in mice. Using immunoblotting and immunostaining, we found that TBI resulted in an increase in the CSPGs neurocan and NG2 expression in a tight band surrounding the injury core, which overlapped with the presence of 4-sulfated CS GAGs but not with 6-sulfated GAGs. This increase was observed as early as 7 days post injury (dpi), and persisted up to 28 dpi. Labeling with markers against microglia/macrophages, NG2 + cells, fibroblasts and astrocytes showed that these cells were all localized in the area, suggesting multiple origins of chondroitin-4-sultate increase. TBI also caused a decrease in the expression of aggrecan and phosphacan in the pericontusional cortex with a concomitant reduction in the number of perineuronal nets. In summary, we describe a dual response in CSPGs where they may be actively involved in complex repair processes following TBI. INDEXING TERMSChondroitin sulfate proteoglycan; traumatic brain injury; extracellular matrix; perineuronal nets

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Section: Discussionsupporting

confidence: 92%

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Katagiri

Susarla

et al. 2012

J of Comparative Neurology

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“…The tight band of 4S CSPG staining around the injury core following CCI is associated with the core proteins neurocan and NG2. Increased neurocan expression is consistent with other reports showing induction of neurocan levels following different types of insults to the mammalian central nervous system, including a knife wound injury to the cortex (Asher et al,2000,2002) and a contusion injury to the spinal cord (Andrews et al,2012; Massey et al,2008) as well as inflammatory insults (Sajad et al,2011) and chronic glial scars (McKeon et al,1999). In cell culture, neurocan is anti‐adhesive and can effectively repel axons, and these actions were effectively abrogated after treatment of neurocan with chondroitinase ABC, supporting a primary role of GAG chains in actions of neurocan (Friedlander et al,1994).…”

Section: Discussionsupporting

confidence: 89%

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Katagiri

Susarla

et al. 2012

J of Comparative Neurology

View full text Add to dashboard Cite

Chondroitin sulfate proteoglycans (CSPGs) play a pivotal role in many neuronal growth mechanisms including axon guidance and the modulation of repair processes following injury to the spinal cord or brain. Many actions of CSPGs in the central nervous system (CNS) are governed by the specific sulfation pattern on the glycosaminoglycan (GAG) chains attached to CSPG core proteins. To elucidate the role of CSPGs and sulfated GAG chains following traumatic brain injury (TBI), controlled cortical impact injury of mild to moderate severity was performed over the left sensory motor cortex in mice. Using immunoblotting and immunostaining, we found that TBI resulted in an increase in the CSPGs neurocan and NG2 expression in a tight band surrounding the injury core, which overlapped with the presence of 4-sulfated CS GAGs but not with 6-sulfated GAGs. This increase was observed as early as 7 days post injury (dpi), and persisted up to 28 dpi. Labeling with markers against microglia/macrophages, NG2+ cells, fibroblasts and astrocytes showed that these cells were all localized in the area, suggesting multiple origins of chondroitin-4-sultate increase. TBI also caused a decrease in the expression of aggrecan and phosphacan in the pericontusional cortex with a concomitant reduction in the number of perineuronal nets. In summary, we describe a dual response in CSPGs where they may be actively involved in complex repair processes following TBI.

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“…In another model of RR EAE (induced with MOG in C57BL/6 mice) (32,33), it was demonstrated that EAE enhanced the migration of SVZ-derived neural stem/progenitor cells (NSC) to the olfactory bulbs and that the adult mouse SVZ is a source of newly generated oligodendrocytes that may contribute, along with oligodendrocyte precursors, to the replacement of oligodendrocytes in inflammatory demyelinating diseases of the CNS. Because it is highly probable that the same would be valid for RR EAE in SJL/J mice, the activated NSC could then express the TSPO, which would reflect the increased uptake of 18 F-PBR111.…”

Section: Discussionmentioning

confidence: 99%

Central Nervous System Expression and PET Imaging of the Translocator Protein in Relapsing–Remitting Experimental Autoimmune Encephalomyelitis

et al. 2013

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Glial neuroinflammation is associated with the development and progression of multiple sclerosis. PET imaging offers a unique opportunity to evaluate neuroinflammatory processes longitudinally in a noninvasive and clinically translational manner. 18 F-PBR111 is a newly developed PET radiopharmaceutical with high affinity and selectivity for the translocator protein (TSPO), expressed on activated glia. This study aimed to investigate neuroinflammation at different phases of relapsing-remitting (RR) experimental autoimmune encephalomyelitis (EAE) in the brains of SJL/J mice by postmortem histologic analysis and in vivo by PET imaging with 18 F-PBR111. Methods: RR EAE was induced by immunization with PLP 139-151 peptide in complete Freund's adjuvant. Naive female SJL/J mice and mice immunized with saline-complete Freund's adjuvant were used as controls. The biodistribution of 18 F-PBR111 was measured in 13 areas of the central nervous system and compared with PET imaging results during different phases of RR EAE. The extents of TSPO expression and glial activation were assessed with immunohistochemistry, immunofluorescence, and a real-time polymerase chain reaction. Results: There was significant TSPO expression in all of the central nervous system areas studied at the peak of the first clinical episode and, importantly, at the preclinical stage. In contrast, only a few TSPO-positive cells were observed at the second episode. At the third episode, there was again an increase in TSPO expression. TSPO expression was associated with microglial cells or macrophages without obvious astrocyte labeling. The dynamics of 18 F-PBR111 uptake in the brain, as measured by in vivo PET imaging and biodistribution, followed the pattern of TSPO expression during RR EAE. Conclusion: PET imaging with the TSPO ligand 18 F-PBR111 clearly reflected the dynamics of microglial activation in the SJL/J mouse model of RR EAE. The results are the first to highlight the discrepancy between the clinical symptoms of EAE and TSPO expression in the brain, as measured by PET imaging at the peaks of various EAE episodes. The results suggest a significant role for PET imaging investigations of neuroinflammation in multiple sclerosis and allow for in vivo follow-up of antiinflammatory treatment strategies.

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Upregulation of CSPG3 Accompanies Neuronal Progenitor Proliferation and Migration in EAE

Cited by 17 publications

References 47 publications

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Central Nervous System Expression and PET Imaging of the Translocator Protein in Relapsing–Remitting Experimental Autoimmune Encephalomyelitis

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