Curcumin encapsulated in PAMAM dendrimers for the therapeutic treatment of ischemic stroke in rats
IntroductionIschemic stroke is a devastating neurovascular condition that occurs when cerebral tissue fails to receive an adequate supply of oxygen. Despite being a leading cause of death and disability worldwide, therapeutic interventions are currently limited. Polyamidoamine (PAMAM) dendrimers are...
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Frontiers Media S.A.
2025-01-01
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| author | Justin Stadler Justin Stadler Justin Stadler Lucas G. Garmo Lucas G. Garmo Lucas G. Garmo David Doyle David Doyle David Doyle Chin-I. Cheng Garrett Richardson Garrett Richardson Zain Waheed Zain Waheed Tim Tofan Bhairavi Srinageshwar Bhairavi Srinageshwar Bhairavi Srinageshwar Ajit Sharma Robert B. Petersen Gary L. Dunbar Gary L. Dunbar Gary L. Dunbar Julien Rossignol Julien Rossignol Julien Rossignol |
| author_facet | Justin Stadler Justin Stadler Justin Stadler Lucas G. Garmo Lucas G. Garmo Lucas G. Garmo David Doyle David Doyle David Doyle Chin-I. Cheng Garrett Richardson Garrett Richardson Zain Waheed Zain Waheed Tim Tofan Bhairavi Srinageshwar Bhairavi Srinageshwar Bhairavi Srinageshwar Ajit Sharma Robert B. Petersen Gary L. Dunbar Gary L. Dunbar Gary L. Dunbar Julien Rossignol Julien Rossignol Julien Rossignol |
| author_sort | Justin Stadler |
| collection | DOAJ |
| description | IntroductionIschemic stroke is a devastating neurovascular condition that occurs when cerebral tissue fails to receive an adequate supply of oxygen. Despite being a leading cause of death and disability worldwide, therapeutic interventions are currently limited. Polyamidoamine (PAMAM) dendrimers are nanomolecules commonly used in biomedical applications due to their ability to encapsulate small-molecules and improve their pharmacokinetic properties. Curcumin is known to have anti-inflammatory and antioxidant effects yet suffers from poor solubility and bioavailability. The purpose of this study is to investigate the efficacy of curcumin encapsulated in PAMAM dendrimers as a potential therapeutic treatment for ischemic stroke by studying post-stroke lesion size, astrocyte reactivity, and functional recovery in a rat model of cerebral ischemia.MethodsForty-eight male and female Sprague-Dawley rats (280–380 g) underwent either a 90-min middle cerebral artery occlusion (MCAo) or sham surgery before receiving one of four treatments: (1) Hanks’ balanced salt solution (HBSS) control, (2) empty dendrimer control, (3) curcumin control, or (4) curcumin encapsulated in PAMAM dendrimer. Neurobehavioral outcomes were evaluated at 1-, 3-, 5-, and 7-day post-surgery, after which animals were euthanized on day 8 to assess infarct volume and GFAP immunoreactivity.ResultsAnimals that received formulations containing dendrimers (curcumin encapsulated in dendrimers or empty dendrimers) demonstrated significantly lower levels of GFAP immunoreactivity and improved functional recovery, including weight and neurobehavioral scores, compared to the formulations that did not contain dendrimers (curcumin and HBSS control). Additionally, the dendrimer-curcumin treatment group exhibited a significantly improved paw laterality index over the course of the study compared with the other three treatment groups.ConclusionAlthough the post-stroke administration of curcumin encapsulated in PAMAM dendrimers modulates the astrocytic response and promotes functional recovery following ischemic stroke in rats, its therapeutic benefits may be driven by PAMAM dendrimers as the empty dendrimer treatment group also showed significant improvements post-stroke. Further investigation regarding PAMAM dendrimers in treating neuroinflammatory conditions remains warranted. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-78a73870714d417cbefbbdbff25985512025-01-06T06:59:33ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011210.3389/fcell.2024.14674171467417Curcumin encapsulated in PAMAM dendrimers for the therapeutic treatment of ischemic stroke in ratsJustin Stadler0Justin Stadler1Justin Stadler2Lucas G. Garmo3Lucas G. Garmo4Lucas G. Garmo5David Doyle6David Doyle7David Doyle8Chin-I. Cheng9Garrett Richardson10Garrett Richardson11Zain Waheed12Zain Waheed13Tim Tofan14Bhairavi Srinageshwar15Bhairavi Srinageshwar16Bhairavi Srinageshwar17Ajit Sharma18Robert B. Petersen19Gary L. Dunbar20Gary L. Dunbar21Gary L. Dunbar22Julien Rossignol23Julien Rossignol24Julien Rossignol25College of Medicine, Central Michigan University, Mount Pleasant, MI, United StatesProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI, United StatesField Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, United StatesCollege of Medicine, Central Michigan University, Mount Pleasant, MI, United StatesProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI, United StatesField Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, United StatesCollege of Medicine, Central Michigan University, Mount Pleasant, MI, United StatesProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI, United StatesField Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, United StatesDepartment of Statistics, Actuarial and Data Science, Central Michigan University, Mt. Pleasant, MI, United StatesCollege of Medicine, Central Michigan University, Mount Pleasant, MI, United StatesField Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, United StatesCollege of Medicine, Central Michigan University, Mount Pleasant, MI, United StatesField Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, United StatesSchool of Business, Wayne State University, Detroit, MI, United StatesCollege of Medicine, Central Michigan University, Mount Pleasant, MI, United StatesProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI, United StatesField Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, United StatesDepartment of Chemistry & Biochemistry, Central Michigan University, Mount Pleasant, MI, United StatesCollege of Medicine, Central Michigan University, Mount Pleasant, MI, United StatesProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI, United StatesField Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, United StatesDepartment of Psychology, Central Michigan University, Mount Pleasant, MI, United StatesCollege of Medicine, Central Michigan University, Mount Pleasant, MI, United StatesProgram in Neuroscience, Central Michigan University, Mount Pleasant, MI, United StatesField Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, United StatesIntroductionIschemic stroke is a devastating neurovascular condition that occurs when cerebral tissue fails to receive an adequate supply of oxygen. Despite being a leading cause of death and disability worldwide, therapeutic interventions are currently limited. Polyamidoamine (PAMAM) dendrimers are nanomolecules commonly used in biomedical applications due to their ability to encapsulate small-molecules and improve their pharmacokinetic properties. Curcumin is known to have anti-inflammatory and antioxidant effects yet suffers from poor solubility and bioavailability. The purpose of this study is to investigate the efficacy of curcumin encapsulated in PAMAM dendrimers as a potential therapeutic treatment for ischemic stroke by studying post-stroke lesion size, astrocyte reactivity, and functional recovery in a rat model of cerebral ischemia.MethodsForty-eight male and female Sprague-Dawley rats (280–380 g) underwent either a 90-min middle cerebral artery occlusion (MCAo) or sham surgery before receiving one of four treatments: (1) Hanks’ balanced salt solution (HBSS) control, (2) empty dendrimer control, (3) curcumin control, or (4) curcumin encapsulated in PAMAM dendrimer. Neurobehavioral outcomes were evaluated at 1-, 3-, 5-, and 7-day post-surgery, after which animals were euthanized on day 8 to assess infarct volume and GFAP immunoreactivity.ResultsAnimals that received formulations containing dendrimers (curcumin encapsulated in dendrimers or empty dendrimers) demonstrated significantly lower levels of GFAP immunoreactivity and improved functional recovery, including weight and neurobehavioral scores, compared to the formulations that did not contain dendrimers (curcumin and HBSS control). Additionally, the dendrimer-curcumin treatment group exhibited a significantly improved paw laterality index over the course of the study compared with the other three treatment groups.ConclusionAlthough the post-stroke administration of curcumin encapsulated in PAMAM dendrimers modulates the astrocytic response and promotes functional recovery following ischemic stroke in rats, its therapeutic benefits may be driven by PAMAM dendrimers as the empty dendrimer treatment group also showed significant improvements post-stroke. Further investigation regarding PAMAM dendrimers in treating neuroinflammatory conditions remains warranted.https://www.frontiersin.org/articles/10.3389/fcell.2024.1467417/fullblood-brain barrier (BBB)curcuminischemic strokeneuroinflammationPAMAM dendrimers |
| spellingShingle | Justin Stadler Justin Stadler Justin Stadler Lucas G. Garmo Lucas G. Garmo Lucas G. Garmo David Doyle David Doyle David Doyle Chin-I. Cheng Garrett Richardson Garrett Richardson Zain Waheed Zain Waheed Tim Tofan Bhairavi Srinageshwar Bhairavi Srinageshwar Bhairavi Srinageshwar Ajit Sharma Robert B. Petersen Gary L. Dunbar Gary L. Dunbar Gary L. Dunbar Julien Rossignol Julien Rossignol Julien Rossignol Curcumin encapsulated in PAMAM dendrimers for the therapeutic treatment of ischemic stroke in rats Frontiers in Cell and Developmental Biology blood-brain barrier (BBB) curcumin ischemic stroke neuroinflammation PAMAM dendrimers |
| title | Curcumin encapsulated in PAMAM dendrimers for the therapeutic treatment of ischemic stroke in rats |
| title_full | Curcumin encapsulated in PAMAM dendrimers for the therapeutic treatment of ischemic stroke in rats |
| title_fullStr | Curcumin encapsulated in PAMAM dendrimers for the therapeutic treatment of ischemic stroke in rats |
| title_full_unstemmed | Curcumin encapsulated in PAMAM dendrimers for the therapeutic treatment of ischemic stroke in rats |
| title_short | Curcumin encapsulated in PAMAM dendrimers for the therapeutic treatment of ischemic stroke in rats |
| title_sort | curcumin encapsulated in pamam dendrimers for the therapeutic treatment of ischemic stroke in rats |
| topic | blood-brain barrier (BBB) curcumin ischemic stroke neuroinflammation PAMAM dendrimers |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1467417/full |
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