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Cell death of spinal cord ED1(+) cells in a rat model of multiple sclerosis.

Trifunović D, Djedović N, Lavrnja I, Wendrich KS, Paquet-Durand F, Miljković D - PeerJ (2015)

Bottom Line: Our findings suggest that activated macrophages/microglia of gray matter are less susceptible to cell death induction.Thus, further research on the gray matter macrophages/microglia cell death during EAE is warranted.They should be aimed at identification of the reasons for the observed differences and finding suitable ways to stimulate gray matter activated macrophages/microglia death.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Ophthalmic Research, University of Tuebingen , Tuebingen , Germany.

ABSTRACT
Infiltration of macrophages into the central nervous system and activation of microglia are hallmarks of multiple sclerosis and its animal model-experimental autoimmune encephalomyelitis (EAE). Cell death in EAE has been demonstrated as an essential mechanism in the local regulation of the inflammatory reaction, but also as one of the major factors contributing to the destruction of the nervous tissue. The focus of this study was on detection of cell death among ED1(+) cells (macrophages/activated microglia) in the spinal cord of Dark Agouti rats at the peak of EAE. Cell death was assessed using the TUNEL assay and immunostaining for cleaved caspase 3, as markers for cell death in general and "classical" apoptosis, respectively. Major infiltrates of immune cells were detected both in white matter and gray matter of spinal cords in rats at the disease peak. ED1, TUNEL, and caspase 3 positive cells were detected within, but also outside the infiltrates. There were more dying ED1(+) cells in white matter than in gray matter, both in the general population and in infiltrated regions. The observed discrepancy in the proportion of dying ED1(+) cells in spinal cord gray and white matter indicated that in EAE rat macrophages/microglia within gray matter are less prone to cell death induction. This is of special interest in the context of the increasingly appreciated contribution of spinal cord gray matter inflammation to multiple sclerosis pathogenesis. Our findings suggest that activated macrophages/microglia of gray matter are less susceptible to cell death induction. Alternatively, it can be assumed that intrinsic cell death-inductive mechanisms of nervous tissue differ in white and gray matter. Thus, further research on the gray matter macrophages/microglia cell death during EAE is warranted. They should be aimed at identification of the reasons for the observed differences and finding suitable ways to stimulate gray matter activated macrophages/microglia death.

No MeSH data available.


Related in: MedlinePlus

Experimental autoimmune encephalomyelitis in Dark Agouti rats.DA rats were immunized with SCH + CFA, while controls were non-immunized animals. (A) The time course of the neurological disability score was determined on a daily basis and data are presented as mean clinical score + SEM (n = 9). (B) Representative sections of spinal cords from immunized and control DA rats stained with DAPI as a nuclear marker. Severe inflammatory infiltrates were present in white and gray matter of immunized animals, as defined by the presence of cellular infiltrates stained with DAPI. WM, white matter; GM, gray matter. Scale bars are 200 and 20 µm for lower and higher magnification pictures, respectively.
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fig-1: Experimental autoimmune encephalomyelitis in Dark Agouti rats.DA rats were immunized with SCH + CFA, while controls were non-immunized animals. (A) The time course of the neurological disability score was determined on a daily basis and data are presented as mean clinical score + SEM (n = 9). (B) Representative sections of spinal cords from immunized and control DA rats stained with DAPI as a nuclear marker. Severe inflammatory infiltrates were present in white and gray matter of immunized animals, as defined by the presence of cellular infiltrates stained with DAPI. WM, white matter; GM, gray matter. Scale bars are 200 and 20 µm for lower and higher magnification pictures, respectively.

Mentions: DA rats immunized with SCH + CFA showed first clinical signs of EAE on 8–10 days post immunization, while the disease peak characterized by hind limb paralysis was observed on 12–14 days post immunization. To maximize the chances for a positive detection of cell death markers in immune cells, we focused the analysis on the peak of clinical score when a high number of infiltrated immune cells was to be expected (Fig. 1A). Indeed numerous, confluent foci of inflammation were visible in white and gray matter of the spinal cords at the peak of EAE (Fig. 1B). At the same time, spinal cord sections obtained from non-immunized (control) animals showed no signs of infiltration and are presented for comparison (Fig. 1B).


Cell death of spinal cord ED1(+) cells in a rat model of multiple sclerosis.

Trifunović D, Djedović N, Lavrnja I, Wendrich KS, Paquet-Durand F, Miljković D - PeerJ (2015)

Experimental autoimmune encephalomyelitis in Dark Agouti rats.DA rats were immunized with SCH + CFA, while controls were non-immunized animals. (A) The time course of the neurological disability score was determined on a daily basis and data are presented as mean clinical score + SEM (n = 9). (B) Representative sections of spinal cords from immunized and control DA rats stained with DAPI as a nuclear marker. Severe inflammatory infiltrates were present in white and gray matter of immunized animals, as defined by the presence of cellular infiltrates stained with DAPI. WM, white matter; GM, gray matter. Scale bars are 200 and 20 µm for lower and higher magnification pictures, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581773&req=5

fig-1: Experimental autoimmune encephalomyelitis in Dark Agouti rats.DA rats were immunized with SCH + CFA, while controls were non-immunized animals. (A) The time course of the neurological disability score was determined on a daily basis and data are presented as mean clinical score + SEM (n = 9). (B) Representative sections of spinal cords from immunized and control DA rats stained with DAPI as a nuclear marker. Severe inflammatory infiltrates were present in white and gray matter of immunized animals, as defined by the presence of cellular infiltrates stained with DAPI. WM, white matter; GM, gray matter. Scale bars are 200 and 20 µm for lower and higher magnification pictures, respectively.
Mentions: DA rats immunized with SCH + CFA showed first clinical signs of EAE on 8–10 days post immunization, while the disease peak characterized by hind limb paralysis was observed on 12–14 days post immunization. To maximize the chances for a positive detection of cell death markers in immune cells, we focused the analysis on the peak of clinical score when a high number of infiltrated immune cells was to be expected (Fig. 1A). Indeed numerous, confluent foci of inflammation were visible in white and gray matter of the spinal cords at the peak of EAE (Fig. 1B). At the same time, spinal cord sections obtained from non-immunized (control) animals showed no signs of infiltration and are presented for comparison (Fig. 1B).

Bottom Line: Our findings suggest that activated macrophages/microglia of gray matter are less susceptible to cell death induction.Thus, further research on the gray matter macrophages/microglia cell death during EAE is warranted.They should be aimed at identification of the reasons for the observed differences and finding suitable ways to stimulate gray matter activated macrophages/microglia death.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Ophthalmic Research, University of Tuebingen , Tuebingen , Germany.

ABSTRACT
Infiltration of macrophages into the central nervous system and activation of microglia are hallmarks of multiple sclerosis and its animal model-experimental autoimmune encephalomyelitis (EAE). Cell death in EAE has been demonstrated as an essential mechanism in the local regulation of the inflammatory reaction, but also as one of the major factors contributing to the destruction of the nervous tissue. The focus of this study was on detection of cell death among ED1(+) cells (macrophages/activated microglia) in the spinal cord of Dark Agouti rats at the peak of EAE. Cell death was assessed using the TUNEL assay and immunostaining for cleaved caspase 3, as markers for cell death in general and "classical" apoptosis, respectively. Major infiltrates of immune cells were detected both in white matter and gray matter of spinal cords in rats at the disease peak. ED1, TUNEL, and caspase 3 positive cells were detected within, but also outside the infiltrates. There were more dying ED1(+) cells in white matter than in gray matter, both in the general population and in infiltrated regions. The observed discrepancy in the proportion of dying ED1(+) cells in spinal cord gray and white matter indicated that in EAE rat macrophages/microglia within gray matter are less prone to cell death induction. This is of special interest in the context of the increasingly appreciated contribution of spinal cord gray matter inflammation to multiple sclerosis pathogenesis. Our findings suggest that activated macrophages/microglia of gray matter are less susceptible to cell death induction. Alternatively, it can be assumed that intrinsic cell death-inductive mechanisms of nervous tissue differ in white and gray matter. Thus, further research on the gray matter macrophages/microglia cell death during EAE is warranted. They should be aimed at identification of the reasons for the observed differences and finding suitable ways to stimulate gray matter activated macrophages/microglia death.

No MeSH data available.


Related in: MedlinePlus