Cytoskeletal protein degradation and neurodegeneration evolves differently in males and females following experimental head injury
Autor: | Bradley Snyder, Edward D. Hall, Walter F. Bobrowski, Nancy C. Kupina, Megan Ryan Detloff |
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Rok vydání: | 2003 |
Předmět: |
Male
Silver Staining medicine.medical_specialty Pathology Time Factors Neurofilament Traumatic brain injury Protein degradation Hippocampus Neuroprotection Mice Sex Factors Neurochemical Developmental Neuroscience Neurofilament Proteins Internal medicine medicine Animals Cerebral Cortex biology Head injury Neurodegeneration Brain Spectrin Neurodegenerative Diseases Calpain medicine.disease Corpus Striatum Survival Rate Cytoskeletal Proteins Disease Models Animal Endocrinology Neurology Brain Injuries Disease Progression biology.protein Female Densitometry |
Zdroj: | Experimental Neurology. 180:55-73 |
ISSN: | 0014-4886 |
Popis: | The resulting neuropathological degeneration that occurs following a traumatic brain injury (TBI) is a consequence of both immediate and secondary neurochemical sequelae. Proteolysis of cytoskeletal proteins, triggered by calcium-mediated events, is believed to be a particularly significant contributor to TBI-induced neuronal death. To date, efforts to associate cytoskeletal degradation and neurodegeneration in TBI have been primarily qualitative or semiquantitative. The objectives of this study were (1) to quantitatively describe, over a posttraumatic time course, the relationship and mechanisms of cytoskeletal degradation (Western blot) and neurodegeneration (silver staining) in male and female mice following a moderately severe weight-drop impact-acceleration head injury; (2) to evaluate gender differences in the response to TBI; and (3) to examine the potential therapeutic window for future pharmacological treatment strategies. In male and female mice, we report a close correlation in the time courses of neurofilament M protein degradation and α-spectrin breakdown products (SBDP 150 and 145) with the peak magnitude of neurodegeneration, as quantified by silver staining. Evidence from the increased patterns of SBDPs suggests that both calpain and caspase-3 are involved. In general, males incurred peak protein degradation and neurodegeneration within 3 days after injury, while in females this did not occur until 14 days. The neuroprotective effects of estrogen are believed to be key factors in the superior outcome of female vs male mice following TBI. In mice, the therapeutic window of opportunity for pharmacological intervention aimed at limiting cytoskeletal degradation might be as much as 24 h following injury. Evidence of a protracted time course of cytoskeletal degradation, especially in females, suggests a potential for an extended treatment-duration following TBI. |
Databáze: | OpenAIRE |
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