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10. Transient Middle Cerebral Artery Occlusion with an Intraluminal Suture Enables Reproducible Induction of Ischemic Stroke in Mice

Author

Lemmerman, Luke R., Harris, Hallie N., Balch, Maria H. H., Rincon-Benavides, Maria A., Higuita-Castro, Natalia, Arnold, David W., and Gallego-Perez, Daniel

Subjects
Strategy and Management, Mechanical Engineering, Methods Article, Metals and Alloys, Industrial and Manufacturing Engineering
Abstract

Ischemic stroke is a leading cause of mortality and chronic disability worldwide, underscoring the need for reliable and accurate animal models to study this disease’s pathology, molecular mechanisms of injury, and treatment approaches. As most clinical strokes occur in regions supplied by the middle cerebral artery (MCA), several experimental models have been developed to simulate an MCA occlusion (MCAO), including transcranial MCAO, micro- or macro-sphere embolism, thromboembolisation, photothrombosis, Endothelin-1 injection, and – the most common method for ischemic stroke induction in murine models – intraluminal MCAO. In the intraluminal MCAO model, the external carotid artery (ECA) is permanently ligated, after which a partially-coated monofilament is inserted and advanced proximally to the common carotid artery (CCA) bifurcation, before being introduced into the internal carotid artery (ICA). The coated tip of the monofilament is then advanced to the origin of the MCA and secured for the duration of occlusion. With respect to other MCAO models, this model offers enhanced reproducibility regarding infarct volume and cognitive/functional deficits, and does not require a craniotomy. Here, we provide a detailed protocol for the surgical induction of unilateral transient ischemic stroke in mice, using the intraluminal MCAO model. Graphic abstract: [Image: see text] Overview of the intraluminal monofilament method for transient middle cerebral artery occlusion (MCAO) in mouse.

Published
2022
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12. Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke

Author

Lemmerman, Luke R., primary, Balch, Maria H. H., additional, Moore, Jordan T., additional, Alzate-Correa, Diego, additional, Rincon-Benavides, Maria A., additional, Salazar-Puerta, Ana, additional, Gnyawali, Surya, additional, Harris, Hallie N., additional, Lawrence, William, additional, Ortega-Pineda, Lilibeth, additional, Wilch, Lauren, additional, Risser, Ian B., additional, Maxwell, Aidan J., additional, Duarte-Sanmiguel, Silvia, additional, Dodd, Daniel, additional, Guio-Vega, Gina P., additional, McTigue, Dana M., additional, Arnold, W. David, additional, Nimjee, Shahid M., additional, Sen, Chandan K., additional, Khanna, Savita, additional, Rink, Cameron, additional, Higuita-Castro, Natalia, additional, and Gallego-Perez, Daniel, additional

Published
2021
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13. Nanochannel‐Based Poration Drives Benign and Effective Nonviral Gene Delivery to Peripheral Nerve Tissue

Author

Moore, Jordan T., primary, Wier, Christopher G., additional, Lemmerman, Luke R., additional, Ortega‐Pineda, Lilibeth, additional, Dodd, Daniel J., additional, Lawrence, William R., additional, Duarte‐Sanmiguel, Silvia, additional, Dathathreya, Kavya, additional, Diaz‐Starokozheva, Ludmila, additional, Harris, Hallie N., additional, Sen, Chandan K., additional, Valerio, Ian L., additional, Higuita‐Castro, Natalia, additional, Arnold, William David, additional, Kolb, Stephen J., additional, and Gallego‐Perez, Daniel, additional

Published
2020
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15. Abstract WP70: Aptamer Inhibition of Von Willebrand Factor Ameliorates Ischemic Stroke Burden in a Murine Model of Thromboembolic Stroke

Author

Dornbos, David L, primary, Wheeler, Debra G, additional, Harris, Hallie, additional, Gnyawali, Surya, additional, Huttinger, Allyson, additional, Talentino, Spencer, additional, Venetos, Nicholas, additional, Musgrave, Nicholas, additional, Jones, Cheyenne, additional, Wilson, Jenna, additional, Bratton, Camille, additional, Carlisle, Kendyl, additional, Zweier, Jay L, additional, Sen, Chandan K, additional, Rink, Cameron, additional, and Nimjee, Shahid M, additional

Published
2018
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18. Abstract WP69: Reversible Aptamer Inhibition of Von Willebrand Factor is a Potent Thrombolytic and Ameliorates Stroke Burden Following Vascular Injury Compared to Recombinant Tissue Plasminogen Activator

Author

Dornbos, David L, primary, Harris, Hallie, additional, Gnyawali, Surya, additional, Wheeler, Debra G, additional, Huttinger, Allyson, additional, Venetos, Nicholas, additional, Talentino, Spencer, additional, Vaccaro, Hope, additional, Musgrave, Nicholas, additional, Jones, Cheyenne, additional, Amaya, Pedro, additional, Rink, Cameron, additional, Zweier, Jay L, additional, Sen, Chandan K, additional, and Nimjee, Shahid M, additional

Published
2017
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19. Abstract 187: Reversible Aptamer Inhibition of Von Willebrand Factor is a Potent Thrombolytic and Ameliorates Stroke Burden Following Vascular Injury Compared to Recombinant Tissue Plasminogen Activator

Author

Dornbos, David L, primary, Harris, Hallie, additional, Gnyawali, Surya, additional, Wheeler, Debra G, additional, Huttinger, Allyson, additional, Venetos, Nicholas, additional, Talentino, Spencer, additional, Vaccaro, Hope, additional, Musgrave, Nicholas, additional, Jones, Cheyenne, additional, Amaya, Pedro, additional, Rink, Cameron, additional, Zweier, Jay L, additional, Sen, Chandan K, additional, and Nimjee, Shahid M, additional

Published
2017
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25. Ketogenic Diet Improves Motor Function and Motor Unit Connectivity in Aged C57BL/6 Mice.

Author

Padilla CJ, Harris H, Volek JS, Clark BC, and Arnold WD

Abstract

Objective: Pathological, age-related loss of muscle function, commonly referred to as sarcopenia, contributes to loss of mobility, impaired independence, as well as increased risk of adverse health events. Sarcopenia has been attributed to changes in both neural and muscular integrity during aging. Current treatment options are primarily limited to exercise and dietary protein fortification, but the therapeutic impact of these approaches are often inadequate. Prior work has suggested that a ketogenic diet (KD) might improve healthspan and lifespan in aging mice. Thus, we sought to investigate the effects of a KD on neuromuscular indices of sarcopenia in aged C57BL/6 mice., Design: A randomized, controlled pre-clinical experiment consisting of longitudinal assessments performed starting at 22-months of age (baseline) as well as 2, 6 and 10 weeks after the start of a KD vs. regular chow intervention., Setting: Preclinical laboratory study., Sample Size: Thirty-six 22-month-old mice were randomized into 2 dietary groups: KD [n = 22 (13 female and 9 male)], and regular chow [n = 15 (7 female and 8 male)]., Measurements: Measures included body mass, hindlimb and all limb grip strength, rotarod for motor performance, plantarflexion muscle contractility, motor unit number estimations (MUNE), and repetitive nerve stimulation (RNS) as an index of neuromuscular junction transmission efficacy recorded from the gastrocnemius muscle. At end point, blood samples were collected to assess blood beta-hydroxybutyrate levels., Statistical Analysis: Two-way ANOVA mixed-effects analysis (time x diet) were performed to analyze grip, rotarod, MUNE, and muscle contractility data., Results: Beta-hydroxybutyrate (BHB) was significantly higher at 10 weeks in mice on a KD vs control group (0.83 ± 0.44 mmol/l versus 0.42 ± 0.21 mmol/l, η 2 = 0.265, unpaired t-test, p = 0.0060). Mice on the KD intervention demonstrated significantly increased hindlimb grip strength (time x diet, p = 0.0030), all limb grip strength (time x diet, p = 0.0523), and rotarod latency to fall (time x diet, p = 0.0021). Mice treated with the KD intervention also demonstrated significantly greater MUNE (time x diet, p = 0.0064), but no difference in muscle contractility (time x diet, p = 0.5836) or RNS (time x diet, p = 0.9871)., Conclusion: KD intervention improved neuromuscular and motor function in aged mice. This pre-clinical work suggests that further research is needed to assess the efficacy and physiological effects of a KD on indices of sarcopenia., Competing Interests: BC Clark reported receiving grants from the National Institutes of Health during the conduct of the study; grants and personal fees from Regeneron Pharmaceuticals; grants from Astellas Global Development Inc, RTI Solutions, NMD Pharma, and OsteoDx Inc; and personal fees from Gerson Lehrman Group; and reported serving as a co-founder and chief of aging research at OsteoDx Inc outside the submitted work. WD Arnold has received grant funding from NMD Pharma and Avidity Biosciences, consulting fees from Avidity Biosciences, NMD Pharma, Dyne Therapeutics, Genentech, Design Therapeutics, Cadent Therapeutics, Catalyst Pharmaceuticals, and from Novartis. JS Volek is a co-founder and stockholder in Virta Health, receives royalties for low-carbohydrate books, and is a scientific advisor for Simply Good Foods and Cook Keto.

Published
2023
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