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Absence of IL-1β positively affects neurological outcome, lesion development and axonal plasticity after spinal cord injury.

Boato F, Rosenberger K, Nelissen S, Geboes L, Peters EM, Nitsch R, Hendrix S - J Neuroinflammation (2013)

Bottom Line: In contrast to our hypothesis, the histological analysis revealed a significantly increased lesion width and a reduced number of corticospinal tract fibers caudal to the lesion center after local application of recombinant IL-1β.Histological analysis revealed a smaller lesion size, reduced lesion width and greatly decreased astrogliosis in the white matter, while the number of corticospinal tract fibers increased significantly 5 mm caudal to the lesion in IL-1βKO mice relative to controls.Our study for the first time characterizes the detrimental effects of IL-1β not only on lesion development (in terms of size and glia activation), but also on the plasticity of central nervous system axons after injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Morphology & BIOMED Institute, Campus Diepenbeek, Hasselt University, Agoralaan Gebouw C, Diepenbeek, BE 3590, Belgium.

ABSTRACT
Precise crosstalk between the nervous and immune systems is important for neuroprotection and axon plasticity after injury. Recently, we demonstrated that IL-1β acts as a potent inducer of neurite outgrowth from organotypic brain slices in vitro, suggesting a potential function of IL-1β in axonal plasticity. Here, we have investigated the effects of IL-1β on axon plasticity during glial scar formation and on functional recovery in a mouse model of spinal cord compression injury (SCI). We used an IL-1β deficiency model (IL-1βKO mice) and administered recombinant IL-1β. In contrast to our hypothesis, the histological analysis revealed a significantly increased lesion width and a reduced number of corticospinal tract fibers caudal to the lesion center after local application of recombinant IL-1β. Consistently, the treatment significantly worsened the neurological outcome after SCI in mice compared with PBS controls. In contrast, the absence of IL-1β in IL-1βKO mice significantly improved recovery from SCI compared with wildtype mice. Histological analysis revealed a smaller lesion size, reduced lesion width and greatly decreased astrogliosis in the white matter, while the number of corticospinal tract fibers increased significantly 5 mm caudal to the lesion in IL-1βKO mice relative to controls. Our study for the first time characterizes the detrimental effects of IL-1β not only on lesion development (in terms of size and glia activation), but also on the plasticity of central nervous system axons after injury.

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Application of recombinant IL-1β and its deficiency influence lesion size after spinal cord compression injury. (A) to (D) Quantification of the lesion size and lesion width based on a clearly distinguishable Iba1-positive area. Lesion size measurement in the central sections of recombinant IL-1β (rIL-1β)-treated mice indicated no difference compared with controls (A), while the lesion width was about 20% greater (B). Both the lesion size (C) and the lesion width (D) were reduced by 40% and 25%, respectively, in IL-1βKO mice compared with controls. (E) Representative micrographs of Iba1 immunoreactive microglia distribution around the compression injury site in spinal cord sections. Upper panels: comparison of PBS-treated and IL-1β-treated spinal cord. Lower panels: comparison of wildtype control with IL-1βKO spinal cord. Dashed line, area of the lesion. Iba1 intensity did not differ significantly between groups (data not shown). *P <0.05; n = 5 mice (PBS), n = 5 mice (rIL-1β), n = 7 mice (C57BL6/J), n = 5 mice (IL-1βKO). Scale bar = 100 μm.
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Figure 8: Application of recombinant IL-1β and its deficiency influence lesion size after spinal cord compression injury. (A) to (D) Quantification of the lesion size and lesion width based on a clearly distinguishable Iba1-positive area. Lesion size measurement in the central sections of recombinant IL-1β (rIL-1β)-treated mice indicated no difference compared with controls (A), while the lesion width was about 20% greater (B). Both the lesion size (C) and the lesion width (D) were reduced by 40% and 25%, respectively, in IL-1βKO mice compared with controls. (E) Representative micrographs of Iba1 immunoreactive microglia distribution around the compression injury site in spinal cord sections. Upper panels: comparison of PBS-treated and IL-1β-treated spinal cord. Lower panels: comparison of wildtype control with IL-1βKO spinal cord. Dashed line, area of the lesion. Iba1 intensity did not differ significantly between groups (data not shown). *P <0.05; n = 5 mice (PBS), n = 5 mice (rIL-1β), n = 7 mice (C57BL6/J), n = 5 mice (IL-1βKO). Scale bar = 100 μm.

Mentions: The rostro-caudal lesion size (mean area on sagittal sections in the center of the lesion) and the lateral lesion width (corresponding to the number of sagittal sections that included the lesion, multiplied by the thickness of each section) were determined by assessing the clearly demarcated Iba1-positive area, but not the sparse Iba1 immunoreactivity present in the surrounding spared tissue (Figure8). Application of rIL-1β did not influence the size of the lesion in the center of the spinal cord (Figure8A), but did result in a lesion almost 100 μm wider compared with PBS-treated mice (from 500 μm in control mice to 600 μm in rIL-1β-treated mice; Figure8B). On the contrary, systemic deficiency of IL-1β resulted in a significantly smaller lesion (almost 40% smaller than in WT mice; Figure8C), as shown in a representative photomicrograph of the center of the lesion (Figure8E lower panels); this was also reflected in a reduced lesion width (25% smaller in IL-1βKO mice; Figure8D).


Absence of IL-1β positively affects neurological outcome, lesion development and axonal plasticity after spinal cord injury.

Boato F, Rosenberger K, Nelissen S, Geboes L, Peters EM, Nitsch R, Hendrix S - J Neuroinflammation (2013)

Application of recombinant IL-1β and its deficiency influence lesion size after spinal cord compression injury. (A) to (D) Quantification of the lesion size and lesion width based on a clearly distinguishable Iba1-positive area. Lesion size measurement in the central sections of recombinant IL-1β (rIL-1β)-treated mice indicated no difference compared with controls (A), while the lesion width was about 20% greater (B). Both the lesion size (C) and the lesion width (D) were reduced by 40% and 25%, respectively, in IL-1βKO mice compared with controls. (E) Representative micrographs of Iba1 immunoreactive microglia distribution around the compression injury site in spinal cord sections. Upper panels: comparison of PBS-treated and IL-1β-treated spinal cord. Lower panels: comparison of wildtype control with IL-1βKO spinal cord. Dashed line, area of the lesion. Iba1 intensity did not differ significantly between groups (data not shown). *P <0.05; n = 5 mice (PBS), n = 5 mice (rIL-1β), n = 7 mice (C57BL6/J), n = 5 mice (IL-1βKO). Scale bar = 100 μm.
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Figure 8: Application of recombinant IL-1β and its deficiency influence lesion size after spinal cord compression injury. (A) to (D) Quantification of the lesion size and lesion width based on a clearly distinguishable Iba1-positive area. Lesion size measurement in the central sections of recombinant IL-1β (rIL-1β)-treated mice indicated no difference compared with controls (A), while the lesion width was about 20% greater (B). Both the lesion size (C) and the lesion width (D) were reduced by 40% and 25%, respectively, in IL-1βKO mice compared with controls. (E) Representative micrographs of Iba1 immunoreactive microglia distribution around the compression injury site in spinal cord sections. Upper panels: comparison of PBS-treated and IL-1β-treated spinal cord. Lower panels: comparison of wildtype control with IL-1βKO spinal cord. Dashed line, area of the lesion. Iba1 intensity did not differ significantly between groups (data not shown). *P <0.05; n = 5 mice (PBS), n = 5 mice (rIL-1β), n = 7 mice (C57BL6/J), n = 5 mice (IL-1βKO). Scale bar = 100 μm.
Mentions: The rostro-caudal lesion size (mean area on sagittal sections in the center of the lesion) and the lateral lesion width (corresponding to the number of sagittal sections that included the lesion, multiplied by the thickness of each section) were determined by assessing the clearly demarcated Iba1-positive area, but not the sparse Iba1 immunoreactivity present in the surrounding spared tissue (Figure8). Application of rIL-1β did not influence the size of the lesion in the center of the spinal cord (Figure8A), but did result in a lesion almost 100 μm wider compared with PBS-treated mice (from 500 μm in control mice to 600 μm in rIL-1β-treated mice; Figure8B). On the contrary, systemic deficiency of IL-1β resulted in a significantly smaller lesion (almost 40% smaller than in WT mice; Figure8C), as shown in a representative photomicrograph of the center of the lesion (Figure8E lower panels); this was also reflected in a reduced lesion width (25% smaller in IL-1βKO mice; Figure8D).

Bottom Line: In contrast to our hypothesis, the histological analysis revealed a significantly increased lesion width and a reduced number of corticospinal tract fibers caudal to the lesion center after local application of recombinant IL-1β.Histological analysis revealed a smaller lesion size, reduced lesion width and greatly decreased astrogliosis in the white matter, while the number of corticospinal tract fibers increased significantly 5 mm caudal to the lesion in IL-1βKO mice relative to controls.Our study for the first time characterizes the detrimental effects of IL-1β not only on lesion development (in terms of size and glia activation), but also on the plasticity of central nervous system axons after injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Morphology & BIOMED Institute, Campus Diepenbeek, Hasselt University, Agoralaan Gebouw C, Diepenbeek, BE 3590, Belgium.

ABSTRACT
Precise crosstalk between the nervous and immune systems is important for neuroprotection and axon plasticity after injury. Recently, we demonstrated that IL-1β acts as a potent inducer of neurite outgrowth from organotypic brain slices in vitro, suggesting a potential function of IL-1β in axonal plasticity. Here, we have investigated the effects of IL-1β on axon plasticity during glial scar formation and on functional recovery in a mouse model of spinal cord compression injury (SCI). We used an IL-1β deficiency model (IL-1βKO mice) and administered recombinant IL-1β. In contrast to our hypothesis, the histological analysis revealed a significantly increased lesion width and a reduced number of corticospinal tract fibers caudal to the lesion center after local application of recombinant IL-1β. Consistently, the treatment significantly worsened the neurological outcome after SCI in mice compared with PBS controls. In contrast, the absence of IL-1β in IL-1βKO mice significantly improved recovery from SCI compared with wildtype mice. Histological analysis revealed a smaller lesion size, reduced lesion width and greatly decreased astrogliosis in the white matter, while the number of corticospinal tract fibers increased significantly 5 mm caudal to the lesion in IL-1βKO mice relative to controls. Our study for the first time characterizes the detrimental effects of IL-1β not only on lesion development (in terms of size and glia activation), but also on the plasticity of central nervous system axons after injury.

Show MeSH
Related in: MedlinePlus