SUR1-TRPM4 Inhibitor Use During Thrombectomy for Stroke Edema
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Ischemic stroke patients, particularly those with large vessel occlusions, face significant challenges from brain swelling due to cellular swelling and ion influx, which complicates treatment and increases the risk of hemorrhage during mechanical thrombectomy, limiting effective interventions like tPA and thrombolytics.
Innovation Solution
Administering a SUR1-TRPM4 channel inhibitor, such as glibenclamide, in combination with mechanical thrombectomy, through continuous infusion over several days, to reduce brain swelling and improve outcomes in patients with large ischemic lesions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If mechanical thrombectomy is performed to restore blood flow, then ischemic damage is reduced, but brain swelling and cerebral edema occur leading to increased intracranial pressure and potential herniation
Solution Approach 1:
The patent applies preliminary action by administering a SUR1-TRPM4 channel inhibitor before and during mechanical thrombectomy procedures. This pre-treatment approach prevents the development of severe brain swelling and cerebral edema that would otherwise occur after reperfusion, thereby enabling safer thrombectomy in patients with large vessel occlusions while reducing the risk of herniation and neurological deterioration
Solution Approach 2:
The SUR1-TRPM4 channel inhibitor acts as an intermediary substance that mediates between the reperfusion process and the harmful effects of brain swelling. By blocking the SUR1-TRPM4 channel, the inhibitor prevents excessive ion influx and cellular swelling during thrombectomy, thus protecting the brain from edema-related damage while allowing beneficial reperfusion to occur
2Productivity
If tPA and other thrombolytics are administered to dissolve clots, then blood flow is restored, but treatment window is narrow and risk of hemorrhage exists
Solution Approach 1:
The patent changes the therapeutic parameter by using a SUR1-TRPM4 channel inhibitor instead of traditional thrombolytics like tPA. This parameter change allows for broader treatment timing flexibility and improved safety profile, as the channel inhibitor works by preventing ion influx and cellular swelling rather than dissolving clots through fibrin degradation, thereby eliminating the narrow time window and hemorrhage risk associated with thrombolytics
3Productivity
If rapid reperfusion is performed in patients with large vessel occlusions, then ischemic tissue is saved, but hemorrhage and adverse effects increase
Solution Approach 1:
The patent applies preliminary action by administering the SUR1-TRPM4 channel inhibitor before rapid reperfusion therapy. This pre-treatment stabilizes the blood-brain barrier and prevents excessive cerebral edema formation, thereby enabling rapid reperfusion in patients with large vessel occlusions while significantly reducing the risk of hemorrhage and other adverse effects that would otherwise occur
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination therapy effectively reduces the risk of neurological deterioration and mortality, improving functional outcomes in patients with large vessel occlusions, even in cases where rapid reperfusion was previously contraindicated.
Implementation Method 1
One ion channel that is associated with cellular swelling is the NCCA-ATP channel, also known as the SUR1-TRPM4 channel. This channel is a non-selective Ca2+ activated ATP sensitive cation channel that is activated when neuronal cells are depleted of intracellular ATP.
Data Source
AI summary
The invention relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors in combination with mechanical thrombectomy. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a lesion volume of less than 140 cm3 or less than 125 cm3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo decompressive therapy.