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Surgical Approach for Middle Cerebral Artery Occlusion and Reperfusion Induced Stroke in Mice
Published on: October 20, 2016
Post-treatment of a BiP inducer prevents cell death after middle cerebral artery occlusion in mice
Yasuhisa Oida1, Junya Hamanaka, Kana Hyakkoku
1Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Abstract:
We previously reported the effect of a selective inducer of BiP (a BiP inducer X; BIX) after permanent middle cerebral artery occlusion (MCAO) in mice. However, in acute stroke, almost all drugs have been used clinically after the onset of events. We evaluated the effect of post-treatment of BIX after permanent MCAO in mice, and examined its neuroprotective properties in in vivo mechanism. BIX (intracerebroventricular injection at 20μg) administered either at 5min or 3h after occlusion reduced both infarct volume and brain swelling, but at 6h after occlusion there was no reduction. BIX protected against the decrease in a dose-dependent manner. Furthermore, BIX reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells induced by the ischemia in ischemic penumbra. These findings indicate that post-treatment with BIX after ischemia has neuroprotective effects against acute ischemic neuronal damage in mice even when given up to 3h after MCAO. BIX may therefore be a potential drug for stroke.
Insights
Post-treatment with BiP inducer X (BIX) up to 3 hours after ischemic stroke in mice reduced brain damage and swelling. This finding suggests BIX is a potential therapeutic drug for acute stroke.
Area of Science:
- Neuroscience
- Pharmacology
- Ischemic Stroke Research
Background:
- Acute ischemic stroke treatment is time-sensitive.
- BiP inducer X (BIX) has shown potential in previous studies.
- Investigating post-treatment efficacy is crucial for clinical translation.
Purpose of the Study:
- To evaluate the neuroprotective effects of BIX post-treatment after permanent middle cerebral artery occlusion (MCAO) in mice.
- To determine the optimal time window for BIX administration.
- To elucidate the in vivo mechanisms of BIX's neuroprotection.
Main Methods:
- Permanent MCAO model in mice.
- Intracerebroventricular injection of BIX at varying time points (5 min, 3 h, 6 h) post-occlusion.
- Measurement of infarct volume and brain swelling.
- Assessment of TUNEL-positive cells in the ischemic penumbra.
Main Results:
- BIX administration at 5 min or 3 h post-MCAO significantly reduced infarct volume and brain swelling.
- No significant reduction was observed when BIX was administered at 6 h post-MCAO.
- BIX demonstrated a dose-dependent protective effect.
- BIX reduced the number of apoptotic cells (TUNEL-positive) in the ischemic penumbra.
Conclusions:
- Post-treatment with BIX up to 3 hours after ischemic stroke exhibits significant neuroprotective effects in a mouse model.
- BIX reduces neuronal apoptosis in the ischemic penumbra.
- BIX is a promising therapeutic candidate for acute ischemic stroke, warranting further investigation.
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