University of Iowa

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Drs. Enrique Leira and Anil Chauhan are co-PIs at the University of Iowa SPAN. Our team has worked efficiently in animal studies with the maximum rigor, involving a multidisciplinary approach of vascular neurologists, animal laboratory surgeons, and imaging facilities. Dr. Chauhan laboratory is very experienced with stroke translational animal studies. Dr. Daniel Thedens is our animal MRI imaging expert. Dr. Angel Chamorro, from the University of Barcelona, an international expert in uric acid, is a collaborator and a consultant in this proposal. Dr. Chauhan’s lab studies the mechanistic role of adhesion molecules in the pathophysiology of brain ischemia/reperfusion injury, particularly in context of thrombo-inflammation.1-4 The approach utilizes experimental models of stroke: filament and embolic models to evaluate stroke outcomes in male and female mice with preexisting comorbidities including hyperlipidemia and aging. Furthermore, the group utilizes state-of-the-art imaging techniques (intravital microscopy, laser-speckle imaging and MRI) and several sensorimotor tests (cylinder test, accelerated rota-rod test, wire-hanging test and corner test) to evaluate long-term functional recovery after stroke.

Publications

1.    Schnell T, Rahmatalla S, DeShaw J, Thedens D, Parker BM, Zimmerman MB, Pieper AA, Chauhan AK, Leira EC. Low-Frequency Vibrations Enhance Thrombolytic Therapy and Improve Stroke Outcomes. Stroke. 2020 Jun;51(6):1855-1861. doi: 10.1161/STROKEAHA.120.029405. Epub 2020 May 13. PMID: 32397935; PMCID: PMC7263385.

2.    Jain M, Tripathi AK, Doddapattar P, Chorawala M, Bathla G, Nayak MK, Ghatge M, Lentz SR, Kon S, Chauhan AK. Targeting Myeloid-Specific Integrin α9β1 Improves Short- and Long-Term Stroke Outcomes in Murine Models With Preexisting Comorbidities by Limiting Thrombosis and Inflammation. Circ Res. 2020 Jun 5;126(12):1779-1794. doi: 10.1161/CIRCRESAHA.120.316659. Epub 2020 Mar 20. PMID: 32195632; PMCID: PMC7274887.

3.    Chorawala MR, Jain M, Bhalla A, Thedens D, Nayak M, Doddapattar P, Chauhan AK. Fn-EDA (Fibronectin Containing Extra Domain A) in the Plasma, but Not Endothelial Cells, Exacerbates Stroke Outcome by Promoting Thrombo-Inflammation. Stroke. 2019 May;50(5):1201-1209. doi: 10.1161/STROKEAHA.118.023697. PMID: 30909835; PMCID: PMC6476677.

4.    Vázquez-Rosa E, Cintrón-Pérez CJ, Thedens D, Kort AJ, Chuong V, Rivera-Dompenciel AM, Chauhan AK, Leira EC, Pieper AA. Treatment with Uric Acid Reduces Infarct and Improves Neurologic Function in Female Mice After Transient Cerebral Ischemia. J Stroke Cerebrovasc Dis. 2018 May;27(5):1412-1416. doi: 10.1016/j.jstrokecerebrovasdis.2017.12.043. Epub 2018 Feb 15. PMID: 29398531.

5.    Prakash P, Doddapattar P, Khanna I, Pollpeter MJ, Nayak MK, Staber JM, Chauhan AK. Endothelial Cell-Derived von Willebrand Factor Is the Major Determinant That Mediates von Willebrand Factor-Dependent Acute Ischemic Stroke by Promoting Postischemic Thrombo-Inflammation. Arterioscler Thromb Vasc Biol. 2016 Sep;36(9):1829-37. doi: 10.1161/ATVBAHA.116.307660. Epub 2016 Jul 21. PMID: 27444201; PMCID: PMC5001895.

6.    Ahmad A, Prakash P, Doddapattar P, Lentz SR, Chauhan AK. Genetic Ablation of Extra Domain A of Fibronectin in Hypercholesterolemic Mice Improves Stroke Outcome by Reducing Thrombo-Inflammation. Circulation. 2015 Dec 8;132(23):2237-47. doi: 10.1161/CIRCULATIONAHA.115.016540. Epub 2015 Oct 27. PMID: 26508731; PMCID: PMC4674336.

7.    Khan MM, Motto DG, Lentz SR, Chauhan AK. ADAMTS13 reduces VWF-mediated acute inflammation following focal cerebral ischemia in mice. J Thromb Haemost. 2012 Aug;10(8):1665-71. doi: 10.1111/j.1538-7836.2012.04822.x. PMID: 22712744; PMCID: PMC3419774.

8.    Khan MM, Gandhi C, Chauhan N, Stevens JW, Motto DG, Lentz SR, Chauhan AK. Alternatively-spliced extra domain A of fibronectin promotes acute inflammation and brain injury after cerebral ischemia in mice. Stroke. 2012 May;43(5):1376-82. doi: 10.1161/STROKEAHA.111.635516. Epub 2012 Feb 23. PMID: 22363055; PMCID: PMC3335936.

9.    Patel RB, Doddapattar P, Ghatge M, Flora GD, Jain M, Thedens D, Olalde H, Kumskova M, Leira EC, Chauhan AK. PKM2 promotes neutrophil activation and cerebral thromboinflammation: therapeutic implications for ischemic stroke. Blood. 2022 Feb 24;139(8):1234-1245. doi: 10.1182/blood.2021012322. PubMed PMID: 34529778; PubMed Central PMCID: PMC8874361.

10.    Garg A, Shaban A, Samaniego EA, Chauhan AK, Leira EC. Risk of Venous Thromboembolism in Hospitalized Patients with Acute Ischemic Stroke Versus Other Neurological Conditions. J Stroke Cerebrovasc Dis. 2021 Nov;30(11):106077. doi: 10.1016/j.jstrokecerebrovasdis.2021.106077. Epub 2021 Sep 6. PubMed PMID: 34500199.


Meet the Team

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Anil Chauhan M. Tech, PhD (co-PI)
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 Enrique Leira MS, MD (co-PI)
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Rakesh Patel, PhD (Post-doc)
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Daniel Thedens, PhD (MRI)
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Mariia Kumskova, MD (Post-doc)
 
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Abhishek Jha, PhD
Aditi Jain M. Tech, PhD (Post-Doc)
Aditi Jain M. Tech, PhD (Post-Doc)