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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

Neurological outcome score in control animals and animals treated with apoptotic MNC-secretomes.Mean neuroscores (±SD) are plotted over time. Treated animals (red triangles for setting 1,Figure 5a, and red squares for setting 2,Figure 5b) improved over time compared to controls (black/white triangles for setting 1,Figure 5a, and black/white squares for setting 2,Figure 5b). Error bars correspond to +/- one standard deviation.
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f5: Neurological outcome score in control animals and animals treated with apoptotic MNC-secretomes.Mean neuroscores (±SD) are plotted over time. Treated animals (red triangles for setting 1,Figure 5a, and red squares for setting 2,Figure 5b) improved over time compared to controls (black/white triangles for setting 1,Figure 5a, and black/white squares for setting 2,Figure 5b). Error bars correspond to +/- one standard deviation.

Mentions: The results from both settings are similar. At time point 6 h there is no significant mean difference in the neuroscores between control and treatment, which is suggested by the coefficient for Treatment. The coefficients for Time 24 h and Time 48 h are not significantly different from zero. We can therefore not conclude that the mean neuroscore in the control group changes with time. The interaction terms for Treatment and Time, however, are significant. This indicates a significant decrease in the mean neuroscore over time in the treatment group. These results correspond well to the graphical depictions of the time curves (Figures 5a and 5b).


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)

Neurological outcome score in control animals and animals treated with apoptotic MNC-secretomes.Mean neuroscores (±SD) are plotted over time. Treated animals (red triangles for setting 1,Figure 5a, and red squares for setting 2,Figure 5b) improved over time compared to controls (black/white triangles for setting 1,Figure 5a, and black/white squares for setting 2,Figure 5b). Error bars correspond to +/- one standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Neurological outcome score in control animals and animals treated with apoptotic MNC-secretomes.Mean neuroscores (±SD) are plotted over time. Treated animals (red triangles for setting 1,Figure 5a, and red squares for setting 2,Figure 5b) improved over time compared to controls (black/white triangles for setting 1,Figure 5a, and black/white squares for setting 2,Figure 5b). Error bars correspond to +/- one standard deviation.
Mentions: The results from both settings are similar. At time point 6 h there is no significant mean difference in the neuroscores between control and treatment, which is suggested by the coefficient for Treatment. The coefficients for Time 24 h and Time 48 h are not significantly different from zero. We can therefore not conclude that the mean neuroscore in the control group changes with time. The interaction terms for Treatment and Time, however, are significant. This indicates a significant decrease in the mean neuroscore over time in the treatment group. These results correspond well to the graphical depictions of the time curves (Figures 5a and 5b).

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