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These studies suggest that treatments for ischemic changes in the brain include nanozymes, baicalein, stem cell therapy, nanomedicines, microglial activation regulation, anti-ischemic drugs, and polyphenolic compounds.
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Recent advancements in nanomedicine have introduced innovative approaches to treat ischemic stroke (IS). A novel peptide-templated MnO2 nanozyme (PNzyme/MnO2) has shown promising results by integrating thrombolytic activity with reactive oxygen species (ROS) scavenging capabilities. This nanozyme can cross the blood-brain barrier, accumulate in ischemic neuronal tissues, and activate thrombolytic functions in the presence of thrombin. In animal models, PNzyme/MnO2 demonstrated prolonged blood circulation, strong thrombolytic action, and reduced ischemic brain damage, while also inhibiting astrocyte activation and pro-inflammatory cytokine secretion.
Baicalein, a flavonoid derived from the root of Scutellaria baicalensis, has been studied for its neuroprotective effects in the subacute phase of ischemic stroke. Administered 24 hours after reperfusion, baicalein significantly reduced neurobehavioral deficits and brain infarct volume in rat models. It also modulated microglia/macrophage polarization, reduced neuroinflammation, and decreased neuronal apoptosis and autophagy, suggesting its potential as a therapeutic agent for cerebral ischemia-reperfusion injury.
Stem cell therapy has emerged as a promising treatment for ischemic brain injury. Various stem cell types have been investigated for their ability to release growth factors, protect blood-brain barrier integrity, and mitigate ischemic injury through exosome release. Intranasal delivery and hypoxic conditioning are potential strategies to optimize stem cell therapy. Preclinical studies have shown that stem cells can down-regulate inflammatory phenotypes and promote tissue regeneration, although clinical trials are still in early phases .
A neutrophil-like cell-membrane-coated mesoporous Prussian blue nanozyme (MPBzyme@NCM) has been developed to target ischemic brain damage noninvasively. This nanozyme improves delivery to the damaged brain and is taken up by microglia, promoting M2 polarization, reducing neutrophil recruitment, and decreasing neuronal apoptosis. This approach shows potential for long-term neurological recovery after ischemic stroke.
Polyphenolic compounds have shown potential in animal models of ischemic stroke due to their biocompatibility and ability to target multiple ischemic cascade signaling pathways. However, their low bioavailability remains a challenge. Strategies to improve bioavailability are being explored to enhance the therapeutic efficacy of polyphenols in clinical settings.
Nanomedicine offers new possibilities for treating ischemic stroke by improving drug pharmacokinetics, achieving effective drug accumulation at target sites, and enhancing therapeutic effects while reducing side effects. Recent research has focused on overcoming barriers to nanomedicine delivery to ischemic lesions and developing new nanomedicine-based treatments.
The treatment of ischemic changes in the brain involves a multifaceted approach, including thrombolytic and neuroprotective strategies, stem cell therapy, and innovative nanomedicine applications. Advances in these areas hold promise for improving outcomes in ischemic stroke patients by targeting various aspects of the ischemic cascade, reducing inflammation, and promoting tissue regeneration. Continued research and clinical trials are essential to translate these promising therapies into effective treatments for patients.
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