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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

Profile of neurotrophic factors in hMNCapo sec and animals treated with hMNCapo sec.(a) ELISA for BDNF, GDNF, and NGF detected only levels of BDNF (356±14pg/mL, mean±SEM) in hMNCapo sec. (b) Six animals received an intraperitoneal injection with hMNCapo sec (n=3, red bar) or control medium (n=3, black/white bar) and BDNF plasma levels were determined 24 hours after administration using ELISA.
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f8: Profile of neurotrophic factors in hMNCapo sec and animals treated with hMNCapo sec.(a) ELISA for BDNF, GDNF, and NGF detected only levels of BDNF (356±14pg/mL, mean±SEM) in hMNCapo sec. (b) Six animals received an intraperitoneal injection with hMNCapo sec (n=3, red bar) or control medium (n=3, black/white bar) and BDNF plasma levels were determined 24 hours after administration using ELISA.

Mentions: In order to characterize the composition of neurotrophic factors present in hMNCapo sec, we performed ELISA for BDNF, GDNF and NGF. Interestingly, only high amounts of BDNF (356±14pg/mL) were detected in hMNCapo sec, suggesting an exclusive role for this neurotrophic factor in hMNCapo sec (Figure 8a).


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)

Profile of neurotrophic factors in hMNCapo sec and animals treated with hMNCapo sec.(a) ELISA for BDNF, GDNF, and NGF detected only levels of BDNF (356±14pg/mL, mean±SEM) in hMNCapo sec. (b) Six animals received an intraperitoneal injection with hMNCapo sec (n=3, red bar) or control medium (n=3, black/white bar) and BDNF plasma levels were determined 24 hours after administration using ELISA.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f8: Profile of neurotrophic factors in hMNCapo sec and animals treated with hMNCapo sec.(a) ELISA for BDNF, GDNF, and NGF detected only levels of BDNF (356±14pg/mL, mean±SEM) in hMNCapo sec. (b) Six animals received an intraperitoneal injection with hMNCapo sec (n=3, red bar) or control medium (n=3, black/white bar) and BDNF plasma levels were determined 24 hours after administration using ELISA.
Mentions: In order to characterize the composition of neurotrophic factors present in hMNCapo sec, we performed ELISA for BDNF, GDNF and NGF. Interestingly, only high amounts of BDNF (356±14pg/mL) were detected in hMNCapo sec, suggesting an exclusive role for this neurotrophic factor in hMNCapo sec (Figure 8a).

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