Intra‐arterial combination therapy for experimental acute ischemic stroke
| Autor: | Michael E. Maniskas, Gregory J. Bix, Jill Roberts, Justin F. Fraser, Amanda A. Gorman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
medicine.medical_specialty
Combination therapy medicine.drug_class Calcium channel blocker RM1-950 Article General Biochemistry Genetics and Molecular Biology Mice chemistry.chemical_compound Pharmacotherapy Piperidines Internal medicine Lubeluzole medicine Animals Infusions Intra-Arterial General Pharmacology Toxicology and Pharmaceutics Ischemic Stroke business.industry Research General Neuroscience Articles General Medicine Ischemic cascade Calcium Channel Blockers Combined Modality Therapy Mice Inbred C57BL Thiazoles Neuroprotective Agents Treatment Outcome Blood pressure Verapamil chemistry Cardiology Therapeutics. Pharmacology Public aspects of medicine RA1-1270 business medicine.drug Combination drug |
| Zdroj: | Clinical and Translational Science, Vol 15, Iss 1, Pp 279-286 (2022) Clinical and Translational Science |
| ISSN: | 1752-8054 1752-8062 |
| Popis: | Acute ischemic stroke continues to devastate millions of individuals worldwide. Current treatments work to restore blood flow but not rescue affected tissue. Our goal was to develop a combination of neuroprotective agents administered intra‐arterially following recanalization to target ischemic tissue. Using C57Bl/6J male mice, we performed tandem transient ipsilateral middle cerebral/common carotid artery occlusion, followed by immediate intra‐arterial pharmacotherapy administration through a standardized protocol. Two pharmacotherapy agents, verapamil and lubeluzole, were selected based on their potential to modulate different aspects of the ischemic cascade; verapamil, a calcium channel blocker, works in an acute fashion blocking L‐type calcium channels, whereas lubeluzole, an N‐methyl‐D‐aspartate modulator, works in a delayed fashion blocking intracellular glutamate trafficking. We hypothesized that combination therapy would provide complimentary and potentially synergistic benefit treating brain tissue undergoing various stages of injury. Physiological measurements for heart rate and pulse distention (blood pressure) demonstrated no detrimental effects between groups, suggesting that the combination drug administration is safe. Tissue analysis demonstrated a significant difference between combination and control (saline) groups in infarct volume, neuronal health, and astrogliosis. Although a significant difference in functional outcome was not observed, we did note that the combination treatment group had a greater percent change from baseline in forced motor movement as compared with controls. This study demonstrates the safety and feasibility of intra‐arterial combination therapy following successful recanalization and warrants further study. |
| Databáze: | OpenAIRE |
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