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Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats with focal ischemia.

Altmann P, Mildner M, Haider T, Traxler D, Beer L, Ristl R, Golabi B, Gabriel C, Leutmezer F, Ankersmit HJ - F1000Res (2014)

Bottom Line: Administration of rat as well as human apoptotic MNC-secretomes significantly reduced ischemic lesion volumes by 36% and 37%, respectively.Co-incubation of human astrocytes, Schwann cells and neurons with hMNC (apo sec) resulted in activation of several signaling cascades associated with the regulation of cytoprotective gene products and enhanced neuronal sprouting in vitro.Analysis of neurotrophic factors in hMNC (apo sec) and rat plasma revealed high levels of brain derived neurotrophic factor (BDNF).

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, 1090, Austria.

ABSTRACT
The pursuit of targeting multiple pathways in the ischemic cascade of cerebral stroke is a promising treatment option. We examined the regenerative potential of conditioned medium derived from rat and human apoptotic mononuclear cells (MNC), rMNC (apo sec) and hMNC (apo sec), in experimental stroke. We performed middle cerebral artery occlusion on Wistar rats and administered apoptotic MNC-secretomes intraperitoneally in two experimental settings. Ischemic lesion volumes were determined 48 hours after cerebral ischemia. Neurological evaluations were performed after 6, 24 and 48 hours. Immunoblots were conducted to analyze neuroprotective signal-transduction in human primary glia cells and neurons. Neuronal sprouting assays were performed and neurotrophic factors in both hMNC (apo sec) and rat plasma were quantified using ELISA. Administration of rat as well as human apoptotic MNC-secretomes significantly reduced ischemic lesion volumes by 36% and 37%, respectively. Neurological examinations revealed improvement after stroke in both treatment groups. Co-incubation of human astrocytes, Schwann cells and neurons with hMNC (apo sec) resulted in activation of several signaling cascades associated with the regulation of cytoprotective gene products and enhanced neuronal sprouting in vitro. Analysis of neurotrophic factors in hMNC (apo sec) and rat plasma revealed high levels of brain derived neurotrophic factor (BDNF). Our data indicate that apoptotic MNC-secretomes elicit neuroprotective effects on rats that have undergone ischemic stroke.

No MeSH data available.


Related in: MedlinePlus

Infarct volumes in control animals and animals treated with apoptotic MNC-secretomes.The percentage of hemispheric lesion volumes (%HLV) are represented as box and whiskers plots, wherein the boxes indicate the 1st and the 2nd quartile and the whiskers the minimum and maximum within 1.5 times the interquartile range from the box.Figure 4a shows lesion volumes as the extend of ischemia in setting 1, where apoptotic MNC-secretomes derived from rats were administered 40 minutes after MCAO compared to controls.Figure 4b corresponds to setting 2, where apoptotic MNC-secretomes derived from humans were administered 40 minutes and 24 hours after MCAO. In both settings, MNCapo sec (red boxes) caused a significant decrease in infarct volumes (*p=0.0006 for setting 1,Figure 4a, and *p=0.0041 for setting 2,Figure 4b) compared to the control group (white boxes) that received only cell culture medium.
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f4: Infarct volumes in control animals and animals treated with apoptotic MNC-secretomes.The percentage of hemispheric lesion volumes (%HLV) are represented as box and whiskers plots, wherein the boxes indicate the 1st and the 2nd quartile and the whiskers the minimum and maximum within 1.5 times the interquartile range from the box.Figure 4a shows lesion volumes as the extend of ischemia in setting 1, where apoptotic MNC-secretomes derived from rats were administered 40 minutes after MCAO compared to controls.Figure 4b corresponds to setting 2, where apoptotic MNC-secretomes derived from humans were administered 40 minutes and 24 hours after MCAO. In both settings, MNCapo sec (red boxes) caused a significant decrease in infarct volumes (*p=0.0006 for setting 1,Figure 4a, and *p=0.0041 for setting 2,Figure 4b) compared to the control group (white boxes) that received only cell culture medium.

Mentions: In a rat model of MCAO we examined the potential of apoptotic MNC-secretomes to reduce ischemic lesion volumes in an allogeneic (experimental setting 1, rMNCapo sec) and a xenogeneic approach (experimental setting 2, hMNCapo sec) (Figure 1). The results of the allogeneic setting displayed significantly lower lesion volumes in the treatment group compared to the control group as shown by TTC-staining (Figure 4). Treatment with rMNCapo sec led to a mean decrease of 36% in total infarct volume. Hemispheric lesion volumes (mean±SD) in the control group were 59%±8% ranging from 50% to 73% (Mann WhitneyU-test; *p=0.0006;Figure 4a). The treatment group had a mean hemispheric lesion volume of 38%±11% ranging from 24% to 51%. In the xenogeneic setting, we injected hMNCapo sec 40 minutes and 24 hours after MCAO. The reduction of the infarction volume in the xenogeneic setting was statistically significant and comparable to that observed in the allogeneic setting (Mann WhitneyU-test; *p=0.0041;Figure 4b). The mean decrease in total infarct volume was 37%. Hemispheric lesion volumes (mean±SD) in the control group were 52%±8% ranging from 42% to 67%. The treatment group had a mean hemispheric lesion volume of 33%±11% ranging from 21% to 48%.


Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats with focal ischemia.

Altmann P, Mildner M, Haider T, Traxler D, Beer L, Ristl R, Golabi B, Gabriel C, Leutmezer F, Ankersmit HJ - F1000Res (2014)

Infarct volumes in control animals and animals treated with apoptotic MNC-secretomes.The percentage of hemispheric lesion volumes (%HLV) are represented as box and whiskers plots, wherein the boxes indicate the 1st and the 2nd quartile and the whiskers the minimum and maximum within 1.5 times the interquartile range from the box.Figure 4a shows lesion volumes as the extend of ischemia in setting 1, where apoptotic MNC-secretomes derived from rats were administered 40 minutes after MCAO compared to controls.Figure 4b corresponds to setting 2, where apoptotic MNC-secretomes derived from humans were administered 40 minutes and 24 hours after MCAO. In both settings, MNCapo sec (red boxes) caused a significant decrease in infarct volumes (*p=0.0006 for setting 1,Figure 4a, and *p=0.0041 for setting 2,Figure 4b) compared to the control group (white boxes) that received only cell culture medium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215751&req=5

f4: Infarct volumes in control animals and animals treated with apoptotic MNC-secretomes.The percentage of hemispheric lesion volumes (%HLV) are represented as box and whiskers plots, wherein the boxes indicate the 1st and the 2nd quartile and the whiskers the minimum and maximum within 1.5 times the interquartile range from the box.Figure 4a shows lesion volumes as the extend of ischemia in setting 1, where apoptotic MNC-secretomes derived from rats were administered 40 minutes after MCAO compared to controls.Figure 4b corresponds to setting 2, where apoptotic MNC-secretomes derived from humans were administered 40 minutes and 24 hours after MCAO. In both settings, MNCapo sec (red boxes) caused a significant decrease in infarct volumes (*p=0.0006 for setting 1,Figure 4a, and *p=0.0041 for setting 2,Figure 4b) compared to the control group (white boxes) that received only cell culture medium.
Mentions: In a rat model of MCAO we examined the potential of apoptotic MNC-secretomes to reduce ischemic lesion volumes in an allogeneic (experimental setting 1, rMNCapo sec) and a xenogeneic approach (experimental setting 2, hMNCapo sec) (Figure 1). The results of the allogeneic setting displayed significantly lower lesion volumes in the treatment group compared to the control group as shown by TTC-staining (Figure 4). Treatment with rMNCapo sec led to a mean decrease of 36% in total infarct volume. Hemispheric lesion volumes (mean±SD) in the control group were 59%±8% ranging from 50% to 73% (Mann WhitneyU-test; *p=0.0006;Figure 4a). The treatment group had a mean hemispheric lesion volume of 38%±11% ranging from 24% to 51%. In the xenogeneic setting, we injected hMNCapo sec 40 minutes and 24 hours after MCAO. The reduction of the infarction volume in the xenogeneic setting was statistically significant and comparable to that observed in the allogeneic setting (Mann WhitneyU-test; *p=0.0041;Figure 4b). The mean decrease in total infarct volume was 37%. Hemispheric lesion volumes (mean±SD) in the control group were 52%±8% ranging from 42% to 67%. The treatment group had a mean hemispheric lesion volume of 33%±11% ranging from 21% to 48%.

Bottom Line: Administration of rat as well as human apoptotic MNC-secretomes significantly reduced ischemic lesion volumes by 36% and 37%, respectively.Co-incubation of human astrocytes, Schwann cells and neurons with hMNC (apo sec) resulted in activation of several signaling cascades associated with the regulation of cytoprotective gene products and enhanced neuronal sprouting in vitro.Analysis of neurotrophic factors in hMNC (apo sec) and rat plasma revealed high levels of brain derived neurotrophic factor (BDNF).

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, 1090, Austria.

ABSTRACT
The pursuit of targeting multiple pathways in the ischemic cascade of cerebral stroke is a promising treatment option. We examined the regenerative potential of conditioned medium derived from rat and human apoptotic mononuclear cells (MNC), rMNC (apo sec) and hMNC (apo sec), in experimental stroke. We performed middle cerebral artery occlusion on Wistar rats and administered apoptotic MNC-secretomes intraperitoneally in two experimental settings. Ischemic lesion volumes were determined 48 hours after cerebral ischemia. Neurological evaluations were performed after 6, 24 and 48 hours. Immunoblots were conducted to analyze neuroprotective signal-transduction in human primary glia cells and neurons. Neuronal sprouting assays were performed and neurotrophic factors in both hMNC (apo sec) and rat plasma were quantified using ELISA. Administration of rat as well as human apoptotic MNC-secretomes significantly reduced ischemic lesion volumes by 36% and 37%, respectively. Neurological examinations revealed improvement after stroke in both treatment groups. Co-incubation of human astrocytes, Schwann cells and neurons with hMNC (apo sec) resulted in activation of several signaling cascades associated with the regulation of cytoprotective gene products and enhanced neuronal sprouting in vitro. Analysis of neurotrophic factors in hMNC (apo sec) and rat plasma revealed high levels of brain derived neurotrophic factor (BDNF). Our data indicate that apoptotic MNC-secretomes elicit neuroprotective effects on rats that have undergone ischemic stroke.

No MeSH data available.


Related in: MedlinePlus