A Clinically Relevant Thromboembolic Stroke Model in the Aged Rat

Animal models have been an integral component of scientific discovery concerning ischemic stroke pathophysiology and the accompanying therapeutic targets. Unfortunately, the knowledge gleaned from these studies has failed to translate to enhanced therapeutics in the clinical environment [O’Collins VE, Macleod MR, Donnan Ga, Horky LL, van der Worp BH, Howells DW, Ann Neurol 59: 467–477, 2006]. We argue that this failed translation is a direct result of inadequate animal models that fail to address the greatest risk factor for stroke, age [Rosen CL, Dinapoli VA, Nagamine T, Crocco T, J Neurosurg 103:687–694, 2005]. Herein we provide comprehensive step-by-step instructions for a clinically relevant thromboembolic stroke model in aged rats [Dinapoli VA, Rosen CL, Nagamine T, Crocco T, J Neurosci Methods 154: 233–238, 2006]. This technique, utilizing the only FDA-approved therapeutic agent for the treatment of stroke, tissue plasminogen activator (tPA), allows for pathophysiologic studies in addition to testing potential therapeutic agents in combination with the currently approved treatment regimen.