Effects of long-term elevated serum levels of growth hormone on life expectancy of mice: Lessons from transgenic animal models

1993 ◽  
Vol 68 (1-3) ◽  
pp. 71-87 ◽  
Author(s):  
Eckhard Wolf ◽  
Eva Kahnt ◽  
Jörn Ehrlein ◽  
Walter Hermanns ◽  
Gottfried Brem ◽  
...  
Author(s):  
Bianca Mages ◽  
Thomas Fuhs ◽  
Susanne Aleithe ◽  
Alexandra Blietz ◽  
Constance Hobusch ◽  
...  

AbstractIn the setting of ischemic stroke, the neurofilament subunit NF-L and the microtubule-associated protein MAP2 have proven to be exceptionally ischemia-sensitive elements of the neuronal cytoskeleton. Since alterations of the cytoskeleton have been linked to the transition from reversible to irreversible tissue damage, the present study investigates underlying time- and region-specific alterations of NF-L and MAP2 in different animal models of focal cerebral ischemia. Although NF-L is increasingly established as a clinical stroke biomarker, MAP2 serum measurements after stroke are still lacking. Therefore, the present study further compares serum levels of MAP2 with NF-L in stroke patients. In the applied animal models, MAP2-related immunofluorescence intensities were decreased in ischemic areas, whereas the abundance of NF-L degradation products accounted for an increase of NF-L-related immunofluorescence intensity. Accordingly, Western blot analyses of ischemic areas revealed decreased protein levels of both MAP2 and NF-L. The cytoskeletal alterations are further reflected at an ultrastructural level as indicated by a significant reduction of detectable neurofilaments in cortical axons of ischemia-affected areas. Moreover, atomic force microscopy measurements confirmed altered mechanical properties as indicated by a decreased elastic strength in ischemia-affected tissue. In addition to the results from the animal models, stroke patients exhibited significantly elevated serum levels of MAP2, which increased with infarct size, whereas serum levels of NF-L did not differ significantly. Thus, MAP2 appears to be a more sensitive stroke biomarker than NF-L, especially for early neuronal damage. This perspective is strengthened by the results from the animal models, showing MAP2-related alterations at earlier time points compared to NF-L. The profound ischemia-induced alterations further qualify both cytoskeletal elements as promising targets for neuroprotective therapies.


2005 ◽  
Vol 1739 (2-3) ◽  
pp. 251-259 ◽  
Author(s):  
Virginia M.-Y. Lee ◽  
Theresa K. Kenyon ◽  
John Q. Trojanowski

Author(s):  
Sneha Shree ◽  
Rajat Bhardwaj ◽  
Kashish ◽  
Rahul Deshmukh

Author(s):  
Victoria Hampshire ◽  
John Bacher ◽  
Melvin Dennis ◽  
Axel Wolff ◽  
Melissa Yarko

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