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Intra-Arterial Delivery of Neural Stem Cells to the Rat and Mouse Brain: Application to Cerebral Ischemia
Published on: June 26, 2020
Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model
Samantha E Spellicy1,2, Erin E Kaiser1,2, Michael M Bowler1
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA.
Abstract:
Magnetic resonance imaging (MRI) is a clinically relevant non-invasive imaging tool commonly utilized to assess stroke progression in real time. This study investigated the utility of MRI as a predictive measure of clinical and functional outcomes when a stroke intervention is withheld or provided, in order to identify biomarkers for stroke functional outcome under these conditions. Fifteen MRI and ninety functional parameters were measured in a middle cerebral artery occlusion (MCAO) porcine ischemic stroke model. Multiparametric analysis of correlations between MRI measurements and functional outcome was conducted. Acute axial and coronal midline shift (MLS) at 24 h post-stroke were associated with decreased survival and recovery measured by modified Rankin scale (mRS) and were significantly correlated with 52 measured acute (day 1 post) and chronic (day 84 post) gait and behavior impairments in non-treated stroked animals. These results suggest that MLS may be an important non-invasive biomarker that can be used to predict patient outcomes and prognosis as well as guide therapeutic intervention and rehabilitation in non-treated animals and potentially human patients that do not receive interventional treatments. Neural stem cell-derived extracellular vesicle (NSC EV) was a disruptive therapy because NSC EV administration post-stroke disrupted MLS correlations observed in non-treated stroked animals. MLS was not associated with survival and functional outcomes in NSC EV-treated animals. In contrast to untreated animals, NSC EVs improved stroked animal outcomes regardless of MLS severity.
Insights
Midline shift (MLS) on MRI predicts stroke outcomes in untreated animals. Neural stem cell-derived extracellular vesicles (NSC EVs) improved outcomes, disrupting MLS-outcome correlations and benefiting all animals.
Area of Science:
- Neurology
- Biomarkers
- Medical Imaging
Background:
- Magnetic resonance imaging (MRI) is crucial for real-time stroke assessment.
- Identifying predictive biomarkers for stroke outcomes is essential for guiding treatment and rehabilitation.
- Current methods for predicting functional recovery post-stroke require further refinement.
Purpose of the Study:
- To investigate MRI as a predictive measure of clinical and functional outcomes in a porcine ischemic stroke model.
- To identify novel biomarkers for stroke functional outcome.
- To evaluate the impact of withholding or providing stroke intervention on MRI-based outcome prediction.
Main Methods:
- Utilized a middle cerebral artery occlusion (MCAO) porcine ischemic stroke model.
- Measured fifteen MRI and ninety functional parameters.
- Conducted multiparametric analysis correlating MRI measurements with functional outcomes.
Main Results:
- Acute midline shift (MLS) at 24 hours post-stroke correlated with decreased survival and functional recovery (mRS) in untreated animals.
- MLS was significantly associated with acute and chronic gait and behavioral impairments in non-treated animals.
- Neural stem cell-derived extracellular vesicle (NSC EV) treatment disrupted MLS-outcome correlations and improved outcomes irrespective of MLS severity.
Conclusions:
- Midline shift (MLS) on MRI serves as a potential non-invasive biomarker for predicting stroke patient outcomes and prognosis.
- MLS may guide therapeutic interventions and rehabilitation strategies, particularly in patients not receiving acute treatments.
- NSC EV therapy offers a promising approach to improve stroke recovery, independent of initial imaging biomarkers like MLS.
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