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Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery
Published on: August 16, 2019
Cell death in an ischemic infarct rim model
Hang Yao1, Xiaolu Sun, Xiang Gu
1Department of Pediatrics (Section of Respiratory Medicine), University of California, San Diego, La Jolla, California, USA.
Journal of Neurochemistry
|August 31, 2007
Summary
Investigating astrocyte-rich areas (ARA) in hippocampal slice cultures, this study found that specific ion changes and DIDS protect against ischemic cell death. These findings offer insights into neuroprotection strategies for stroke.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Ischemic stroke causes significant neuronal damage, particularly in the hippocampus.
- The microenvironment of the ischemic infarct rim plays a critical role in cell death mechanisms.
- Astrocyte-rich areas (ARA) within the hippocampus are vulnerable to ischemic injury.
Purpose of the Study:
- To investigate the temporal profile and mechanisms of cell death in the astrocyte-rich area (ARA) of hippocampal slice cultures under ischemic conditions.
- To evaluate the protective effects of specific ion concentrations and DIDS on cell survival in ARA.
- To elucidate the role of ion transport and signaling pathways in ischemic injury within the hippocampus.
Main Methods:
- Organotypic hippocampal slice cultures were used to simulate the in vitro ischemic infarct rim microenvironment.
- Two-photon confocal microscopy, propidium iodide staining, and GFAP-GFP transgenic mice were employed to assess cell death in astrocytes.
- An 'ischemic solution' (IS) was utilized, with subsequent ion replacements (K+, Cl-, HCO3-) and the application of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) to study protective mechanisms.
Main Results:
- Ischemic solution induced significant cell death in the hippocampus, with earliest injury observed in ARA.
- Increased extracellular potassium (K+) and lowered pH showed modest protection in ARA, with high K+ being most effective when bicarbonate (HCO3-) levels were normal or high.
- Reduced chloride (Cl-) or bicarbonate (HCO3-) exacerbated cell injury, while DIDS demonstrated dose-dependent protection against IS-induced death.
Conclusions:
- Different hippocampal regions exhibit varying responses to ionic alterations during ischemia.
- Potassium ions (K+) interact with other ions to confer protection to cells in ARA.
- DIDS provides substantial protection in ARA, likely by inhibiting specific membrane exchangers or interfering with intracellular signaling pathways, highlighting its potential therapeutic relevance.
