Differential regulation of the CXCR2 chemokine network in rat brain trauma: Implications for neuroimmune interactions and neuronal survival

Vallès, Astrid; Grijpink-Ongering, Lindsay; Bree, F.M. de; Tuinstra, T.; Ronken, Eric

doi:10.1016/j.nbd.2005.11.015

Cited by 82 publications

(56 citation statements)

References 53 publications

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“…In contrast, CXCR2 was absent on resting monocytes/microglia and is upregulated upon activation of these cells during demyelination. Such a differential regulation of CXCR2 on monocytes/microglia has also been observed in experimental stroke (Popivanova, 2003) and CNS injury (Valles, 2006). Thus, upregulation of CXCR2 on microglia in the CNS seems to be a rather unspecific consequence of microglial activation after various stimuli, including toxic demyelination.…”

Section: Discussionmentioning

confidence: 74%

The chemokine receptor CXCR2 is differentially regulated on glial cells in vivo but is not required for successful remyelination after cuprizone‐induced demyelination

Lindner

Trebst

Heine

et al. 2008

Glia

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Unravelling the factors that can positively influence remyelination is one of the major challenges in multiple sclerosis research. Expression of the chemokine receptor CXCR2 on oligodendrocytes both in vitro and in MS lesions has suggested a possible role for CXCR2 in the recruitment of oligodendrocyte precursor cells (OPC). To investigate the function of CXCR2 during remyelination in vivo, we studied this receptor in cuprizone-induced demyelination and subsequent remyelination. We found that CXCR2 is constitutively expressed on OPC, whereas on macrophages/microglia CXCR2 is upregulated upon activation during demyelination. Hence, the expression of CXCR2 is differentially regulated in oligodendrocytes and macrophages/microglia. Furthermore, we subjected CXCR2-/- mice to the cuprizone model demonstrating that remyelination was not altered in comparison to wildtype controls. In addition, the number of OPC and the amount of microglial accumulation were similar in both CXCR2-/- and wildtype animals during the whole demyelination and remyelination process. These results suggest that despite expression on OPC and microglia CXCR2 plays only a minor role during remyelination.

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Section: Discussionmentioning

confidence: 74%

The chemokine receptor CXCR2 is differentially regulated on glial cells in vivo but is not required for successful remyelination after cuprizone‐induced demyelination

Lindner

Trebst

Heine

et al. 2008

Glia

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“…These effects may facilitate faster and more thorough penetration by cytokines into the sampled brain tissue in trephine compared to the drill rats, potentially accounting for the increases in KC-GRO and IL-1b noted above. KC-GRO levels are increased at early time points post-injury in closed-head injury models (Semple et al, 2010a(Semple et al, , 2010bValles et al, 2006). The increase in the expression of this protein in both craniotomy groups suggests that the sham procedure itself can induce a confounding factor if this research is repeated using an open-head injury model.…”

Section: Discussionmentioning

confidence: 96%

Craniotomy: True Sham for Traumatic Brain Injury, or a Sham of a Sham?

Cole

Yarnell

Kean

et al. 2011

Journal of Neurotrauma

252

197

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Neurological dysfunction after traumatic brain injury (TBI) is caused by both the primary injury and a secondary cascade of biochemical and metabolic events. Since TBI can be caused by a variety of mechanisms, numerous models have been developed to facilitate its study. The most prevalent models are controlled cortical impact and fluid percussion injury. Both typically use ''sham'' (craniotomy alone) animals as controls. However, the sham operation is objectively damaging, and we hypothesized that the craniotomy itself may cause a unique brain injury distinct from the impact injury. To test this hypothesis, 38 adult female rats were assigned to one of three groups: control (anesthesia only); craniotomy performed by manual trephine; or craniotomy performed by electric dental drill. The rats were then subjected to behavioral testing, imaging analysis, and quantification of cortical concentrations of cytokines. Both craniotomy methods generate visible MRI lesions that persist for 14 days. The initial lesion generated by the drill technique is significantly larger than that generated by the trephine. Behavioral data mirrored lesion volume. For example, drill rats have significantly impaired sensory and motor responses compared to trephine or naïve rats. Finally, of the seven tested cytokines, KC-GRO and IFN-c showed significant increases in both craniotomy models compared to naïve rats. We conclude that the traditional sham operation as a control confers profound proinflammatory, morphological, and behavioral damage, which confounds interpretation of conventional experimental brain injury models. Any experimental design incorporating ''sham'' procedures should distinguish among sham, experimentally injured, and healthy/naïve animals, to help reduce confounding factors.

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“…There are few previous studies on the role of this cytokine in DRG, though it has been shown to enhance peptide release from neonatal DRG nociceptors in vitro and to induce hyperalgesia after peripheral injection (Qin et al, 2005). However, GRO/KC has been implicated in several CNS pathologies (e.g., Xia and Hyman, 2002, Losy et al, 2005, Valles et al, 2006, and can acutely modulate activity of cerebella neurons (Giovannelli et al, 1998). Similarly, there are few studies on the role of IL-18 in DRG, though it has been extensively studied in models of various CNS pathologies (Felderhoff-Mueser et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Robust increase of cutaneous sensitivity, cytokine production and sympathetic sprouting in rats with localized inflammatory irritation of the spinal ganglia

et al. 2006

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We investigated the role and mechanisms of inflammatory responses within the dorsal root ganglion (DRG) in the development of chemogenic pathological pain. DRG inflammation was induced by a single deposit of the immune activator zymosan in incomplete Freund's adjuvant in the epidural space near the L5 DRG via a small hole drilled through the transverse process. After a single zymosan injection, rats developed bilateral mechanical hyperalgesia and allodynia which began by day 1 after surgery, peaked at days 3-7, and lasted up to 28 days. The number of macrophages in ipsilateral and contralateral DRGs increased significantly, lasting over 14 days. Robust glial activation was observed in inflamed ganglia. Cytokine profile analysis using a multiplexing protein array system showed that, in normal DRG, all but IL-5, IL-10 and GM-CSF were detectable with concentrations of up to 180 pg/mg protein. Local inflammatory irritation selectively increased IL-1β, IL-6, IL-18, MCP-1, and GRO/KC up to 17 fold, and decreased IL-2 and IL-12 (p70) up to 3 fold. Inflaming the DRG also remarkably increased the incidence of spontaneous activity of A-and C-fibers recorded in the dorsal root. Many of the spontaneously active A-fibers exhibited a short-bursting discharge pattern. Changes in cytokines and spontaneous activity correlated with the time course of pain behaviors, especially light stroke-evoked tactile allodynia. Finally, local inflammation induced extensive sprouting of sympathetic fibers, extending from vascular processes within the inflamed DRG. These results demonstrate the feasibility of inducing chronic localized inflammatory responses in the DRG in the absence of traumatic nerve damage, and highlight the possible contribution of several inflammatory cytokines/chemokines to the generation of spontaneous activity and development and persistence of chemogenic pathologic pain.

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Differential regulation of the CXCR2 chemokine network in rat brain trauma: Implications for neuroimmune interactions and neuronal survival

Cited by 82 publications

References 53 publications

The chemokine receptor CXCR2 is differentially regulated on glial cells in vivo but is not required for successful remyelination after cuprizone‐induced demyelination

The chemokine receptor CXCR2 is differentially regulated on glial cells in vivo but is not required for successful remyelination after cuprizone‐induced demyelination

Craniotomy: True Sham for Traumatic Brain Injury, or a Sham of a Sham?

Robust increase of cutaneous sensitivity, cytokine production and sympathetic sprouting in rats with localized inflammatory irritation of the spinal ganglia

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