title: Hyperglycemia, acute ischemic stroke, and thrombolytic therapy.
abstract: Ischemic stroke is a leading cause of disability and is considered now the fourth leading cause of death. Many clinical trials have shown that stroke patients with acute elevation in blood glucose at onset of stroke suffer worse functional outcomes, longer in-hospital stay, and higher mortality rates. The only therapeutic hope for these patients is the rapid restoration of blood flow to the ischemic tissue through intravenous administration of the only currently proven effective therapy, tissue plasminogen activator (tPA). However, even this option is associated with the increased risk of intracerebral hemorrhage. Nonetheless, the underlying mechanisms through which hyperglycemia (HG) and tPA worsen the neurovascular injury after stroke are not fully understood. Accordingly, this review summarizes the latest updates and recommendations about the management of HG and coadministration of tPA in a clinical setting while focusing more on the various experimental models studying (1) the effect of HG on stroke outcomes, (2) the potential mechanisms involved in worsening the neurovascular injury, (3) the different therapeutic strategies employed to ameliorate the injury, and finally, (4) the interaction between HG and tPA. Developing therapeutic strategies to reduce the hemorrhage risk with tPA in hyperglycemic setting is of great clinical importance. This can best be achieved by conducting robust preclinical studies evaluating the interaction between tPA and other therapeutics in order to develop potential therapeutic strategies with high translational impact.
authors.affiliation: Charlie Norwood Veterans Administration Medical Center, College of Pharmacy, University of Georgia.|Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia.
authors.forename: Sherif
authors.initials: S
authors.lastname: Hafez
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA.
authors.forename: Maha
authors.initials: M
authors.lastname: Coucha
authors.affiliation: Department of Neurology, Georgia Regents University, Augusta, GA.
authors.forename: Askiel
authors.initials: A
authors.lastname: Bruno
authors.affiliation: Charlie Norwood Veterans Administration Medical Center, College of Pharmacy, University of Georgia.|Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia.|Department of Neurology, Georgia Regents University, Augusta, GA.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
authors.affiliation: Charlie Norwood Veterans Administration Medical Center, College of Pharmacy, University of Georgia.|Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia.|Department of Physiology, Georgia Regents University, Augusta, GA.
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000208:Acute Disease; D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D008297:Male; D051379:Mice; D051381:Rats; D020521:Stroke / Q000150:complications* / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator