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Alterations in hippocampal GAP-43, BDNF, and L1 following sustained cerebral ischemia
Keiko Miyake1, Wataru Yamamoto, Mina Tadokoro
1Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, 192-0392 Hachioji, Japan.
Abstract:
Alterations in factors involved in the regeneration of the neuronal network in the hippocampus of rats with microsphere embolism (ME) were examined. Nine hundred microspheres (48 microm in diameter) were injected into the right hemisphere, and immunochemical and immunohistochemical studies on the hippocampus were performed on the seventh day thereafter. Hematoxylin-eosin staining showed progressive and severe degeneration of the hippocampus after ME. The protein levels of brain-derived neurotrophic factor (BDNF), 43-kDa growth-associated protein (GAP-43), and adhesion protein L1 (L1) in the ipsilateral hippocampus of the ME animal, determined by Western blot analysis or enzyme immunoassay, were increased, unaltered, and decreased, respectively. In contrast, the immunohistochemical study showed increases in a marker of axonal sprouting GAP-43, and a neurotrophic factor BDNF, and a decrease in an adhesion molecule L1 in some areas of the hippocampal ischemic penumbra of such animals. These results suggest that some factors for regeneration of the neuronal network in the ischemic penumbra responded to sustained cerebral ischemia for a certain period, although functional network of the nerve cells in the microsphere-injected hemisphere would be unlikely established after ME.
Insights
Brain-derived neurotrophic factor (BDNF) and GAP-43 increased after microsphere embolism (ME) in rats, while L1 decreased, indicating some regenerative response in the ischemic penumbra despite severe hippocampal degeneration.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Regenerative Medicine
Background:
- Neuronal network regeneration is crucial for recovery after ischemic stroke.
- The hippocampus is highly vulnerable to ischemic injury.
- Understanding molecular changes post-ischemia aids therapeutic development.
Purpose of the Study:
- To investigate alterations in key regeneration factors in the hippocampus following microsphere embolism (ME) in rats.
- To assess the expression of brain-derived neurotrophic factor (BDNF), GAP-43, and L1 post-ischemia.
- To evaluate the potential for neuronal network regeneration in the ischemic penumbra.
Main Methods:
- Rat model of cerebral ischemia induced by microsphere embolism (ME).
- Hematoxylin-eosin staining for histological assessment of hippocampal degeneration.
- Western blot and enzyme immunoassay for protein level analysis of BDNF, GAP-43, and L1.
- Immunohistochemistry to localize changes in the ischemic penumbra.
Main Results:
- ME caused severe progressive degeneration of the hippocampus.
- Protein levels of BDNF and GAP-43 increased, while L1 decreased in the ipsilateral hippocampus.
- Immunohistochemistry revealed increased axonal sprouting marker (GAP-43) and neurotrophic factor (BDNF) in the ischemic penumbra, with decreased L1.
- These changes suggest a partial regenerative response within the ischemic penumbra.
Conclusions:
- The hippocampus exhibits a complex molecular response to ischemic injury, with some pro-regenerative factors upregulated.
- Despite upregulation of BDNF and GAP-43, severe degeneration and decreased L1 hinder functional neuronal network recovery after ME.
- The findings highlight the limited capacity for functional network restoration in the ischemic penumbra following significant cerebral ischemia.