Diabetes Mellitus/Poststroke Hyperglycemia: a Detrimental Factor for tPA Thrombolytic Stroke Therapy
- PDF / 454,302 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 10 Downloads / 186 Views
REVIEW ARTICLE
Diabetes Mellitus/Poststroke Hyperglycemia: a Detrimental Factor for tPA Thrombolytic Stroke Therapy Yinghua Jiang 1 & Ning Liu 1 & Jinrui Han 1 & Yadan Li 1 & Pierce Spencer 1 & Samuel J. Vodovoz 1 & Ming-Ming Ning 2 & Gregory Bix 1 & Prasad V. G. Katakam 3 & Aaron S. Dumont 1 & Xiaoying Wang 1 Received: 30 August 2020 / Revised: 20 October 2020 / Accepted: 21 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Intravenous administration of tissue-type plasminogen activator (IV tPA) therapy has long been considered a mainstay in ischemic stroke management. However, patients respond to IV tPA therapy unequally with some subsets of patients having worsened outcomes after treatment. In particular, diabetes mellitus (DM) is recognized as a clinically important vascular comorbidity that leads to lower recanalization rates and increased risks of hemorrhagic transformation (HT). In this short-review, we summarize the recent advances in understanding of the underlying mechanisms involved in post-IV tPA worsening of outcome in diabetic stroke. Potential pathologic factors that are related to the suboptimal tPA recanalization in diabetic stroke include higher plasma plasminogen activator inhibitor (PAI)-1 level, diabetic atherogenic vascular damage, glycation of the tPA receptor annexin A2, and alterations in fibrin clot density. While factors contributing to the exacerbation of HT in diabetic stroke include hyperglycemia, vascular oxidative stress, and inflammation, tPA neurovascular toxicity and imbalance in extracellular proteolysis are discussed. Besides, impaired collaterals in DM also compromise the efficacy of IV tPA therapy. Additionally, several tPA combination approaches developed from experimental studies that may help to optimize IV tPA therapy are also briefly summarized. In summary, more research efforts are needed to improve the safety and efficacy of IV tPA therapy in ischemic stroke patients with DM/poststroke hyperglycemia. Keywords Ischemic stroke . Tissue-type plasminogen activator . Diabetes mellitus . Hyperglycemia . Recanalization rate . Intracerebral hemorrhage
Introduction Ischemic stroke is a serious cerebrovascular event. Despite enormous research efforts that have been put in finding
* Yinghua Jiang [email protected] * Xiaoying Wang [email protected] 1
Clinical Neuroscience Research Center, Departments of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA 70122, USA
2
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
3
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70122, USA
effective approaches for ischemic stroke management, intravenous administration of recombinant tissue plasminogen activator (IV tPA) remains the only FDA-approved pharmacological intervention for emergent management of ischemic stroke [1, 2]. IV tPA therapy is based on the “recanalization
Data Loading...
