Validation of a stroke model in rat compatible with rt-PA-induced thrombolysis: new hope for successful translation to the clinic.

Scientific Reports
Kajsa ArkeliusSaema Ansar

Abstract

The recent clinical trial (DAWN) suggests that recanalization treatment may be beneficial up to 24 h after stroke onset, thus re-opening avenues for development of new therapeutic strategies. Unfortunately, there is a continuous failure of drugs in clinical trials and one of the major reasons proposed for this translational roadblock is the animal models. Therefore, the purpose of this study was to validate a new thromboembolic stroke rat model that mimics the human pathology, and that can be used for evaluating new strategies to save the brain in conditions compatible with recanalization. Stroke was induced by injection of thrombin into the middle cerebral artery. Recombinant tissue-type plasminogen activator (rt-PA) or saline was administrated at 1 h/4 h after stroke onset, and outcome was evaluated after 24 h. Induced ischemia resulted in reproducible cortical brain injuries causing a decrease in neurological function 24 h after stroke onset. Early rt-PA treatment resulted in recanalization, reduced infarct size and improved neurological functions, while late rt-PA treatment showed no beneficial effects and caused hemorrhagic transformation in 25% of the rats. This validated and established model's resemblance to human ische...Continue Reading

References

Jul 1, 1992·Annals of Neurology·G J del ZoppoO Busse
Jan 1, 1985·Stroke; a Journal of Cerebral Circulation·D KanekoT Ogawa
Jul 1, 1982·Stroke; a Journal of Cerebral Circulation·M KudoN Fukunaga
Dec 14, 1995·The New England Journal of Medicine·UNKNOWN National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group
Feb 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Z ZhangM Chopp
Nov 22, 1997·Cellular and Molecular Life Sciences : CMLS·E Di CeraY M Ayala
May 22, 1998·Stroke; a Journal of Cerebral Circulation·L Roberts, C Counsell
Nov 6, 1998·Neuroreport·E KilicK A Hossmann
Apr 27, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·C X WangA Shuaib
Aug 7, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·R M DijkhuizenE H Lo
Feb 12, 2005·Stroke; a Journal of Cerebral Circulation·Raza NoorAshfaq Shuaib
May 11, 2005·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·Michael D HillUNKNOWN Canadian Alteplase for Stroke Effectiveness Study (CASES) Investigators
Feb 3, 2006·Annals of Neurology·Victoria E O'CollinsDavid W Howells
Oct 10, 2006·Artificial Organs·Johannes BoltzeFrank Emmrich
Feb 10, 2007·Stroke; a Journal of Cerebral Circulation·Maher SaqqurUNKNOWN CLOTBUST Investigators
May 25, 2007·Pharmacology, Biochemistry, and Behavior·Aysan Durukan, Turgut Tatlisumak
Jun 26, 2007·Neurological Research·Rune Skovgaard RasmussenGudrun Boysen
Aug 19, 2007·Stroke; a Journal of Cerebral Circulation·Cyrille OrsetDenis Vivien
Aug 23, 2007·ILAR Journal·Jeffrey A KleimDeAnna L Adkins
Sep 26, 2008·The New England Journal of Medicine·Werner HackeUNKNOWN ECASS Investigators
Mar 11, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Benoît HaelewynJacques H Abraini
Sep 21, 2010·Experimental & Translational Stroke Medicine·Karsten OvergaardFlemming F Johansen
Nov 26, 2010·Stroke; a Journal of Cerebral Circulation·Isaac García-YébenesMaría A Moro
Jan 25, 2011·Journal of Neuroscience Methods·Angelo EncarnacionMehrdad Shamloo
Jan 12, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Konstantin-Alexander Hossmann
Sep 13, 2012·Experimental & Translational Stroke Medicine·Friederike L LanghauserMarc Fatar
Apr 18, 2015·The New England Journal of Medicine·Jeffrey L SaverUNKNOWN SWIFT PRIME Investigators
Mar 19, 2016·Stroke; a Journal of Cerebral Circulation·Nicholas H ChiaTimothy J Kleinig
Apr 2, 2016·Stroke; a Journal of Cerebral Circulation·Cyrille OrsetDenis Vivien
Nov 23, 2016·Journal of the Neurological Sciences·Georgios TsivgoulisAnne W Alexandrov
Nov 14, 2017·The New England Journal of Medicine·Raul G NogueiraUNKNOWN DAWN Trial Investigators
Feb 2, 2018·Circulation·Emelia J BenjaminUNKNOWN American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
Jun 15, 2018·European Stroke Journal·Peter McMeekinGary A Ford
Aug 10, 2018·Acta Neurologica Scandinavica·Tatsuya UenoMasahiko Tomiyama
Apr 2, 2020·European Stroke Journal·Ramon Luengo-FernandezJose Leal

❮ Previous
Next ❯

Citations

May 1, 2021·Pharmaceuticals·Jung Hak KimHong Jun Lee

❮ Previous
Next ❯

Software Mentioned

GraphPad Prism
ARRIVE
GraphPad
ImageJ

Related Concepts

Related Feeds

Acute Stroke

A stroke occurs when blood supply to the brain is interrupted depriving the brain of oxygen and nutrients. This feed focuses cerebrovascular accidents including ischemic and paralytic stroke.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.