ORIGINAL ARTICLE Four-vessel occlusion model using aged male Wistar rats: a reliable model to resolve the discrepancy related to age in cerebral ischemia research Jesu ´ s Ancer-Rodrı ´guez 1 • Eliud Enrique Villarreal-Silva 2 • Rodolfo Amador Salazar-Ybarra 2 • Oscar Quiroga-Garcı ´a 2 • Humberto Rodrı ´guez-Rocha 3 • Aracely Garcı ´a-Garcı ´a 3 • Rodolfo Morales-Avalos 2 • Jesu ´s Alberto Morales-Go ´mez 5 • Alejandro Quiroga-Garza 2 • Odila Saucedo-Ca ´rdenas 3 • Zao Cheng Xu 4 • Rodrigo Enrique Elizondo-Oman ˜a 2 • Angel Raymundo Martı ´nez-Ponce-de-Leo ´n 5 • Santos Guzma ´n-Lo ´pez 2 Received: 18 November 2014 / Accepted: 25 April 2015 / Published online: 13 May 2015 Ó Japanese Association of Anatomists 2015 Abstract Animal models of cerebral ischemia have typically been established and performed using young animals, even though cerebral ischemia (CI) affects primarily elderly patients. This situation represents a discrepancy that complicates the translation of novel therapeutic strategies for CI. Models of transient global CI using aged animals have demonstrated an apparent neuroprotective effect on CA1 hippocampal neurons; however, this effect is not completely understood. Our study used a model in which young (3–6 months) and aged (18–21 months) male Wistar rats were subjected to 15 min of transient global CI using the four-vessel oc- clusion (4 VO) model. We determined that the 4 VO model can be performed on aged rats with a slight in- crease in mortality rate. In aged rats, the morphological damage was completely established by the 4th day after reperfusion, displaying no difference from their younger counterparts. These results demonstrated the lack of a neuroprotective effect of aging on CA1 hippocampal neurons in aged male Wistar rats. This study determined and characterized the morphological damage to the CA1 area after 15 min of 4 VO in aged male Wistar rats, validating the use of this model in CI and aging research. Keywords Aging Á Animal models Á Brain ischemia Á Global cerebral ischemia Á Hippocampal CA1 region Introduction In the clinical setting, cerebral ischemia (CI) occurs during stroke and cardiac arrest (CA) and affects primarily elderly patients. In the Western world, more than 70 % of indi- viduals experiencing a stroke and 83 % experiencing a CA are over 65 years old (Zheng et al. 2001; Lakhan et al. 2009). As life expectancy continues to increase, the number of in- dividuals affected by CI will increase further. Studies of CI in experimental animals have demonstrated the neuropro- tective efficacy of a variety of interventions, but most of these interventions have failed to demonstrate any benefit to humans based on clinical trials. A discrepancy related to age is the most apparent potential explanation for these disap- pointing results, because most experimental neuroprotective strategies have been evaluated using young animals, even though CI affects primarily elderly patients (Buga et al. 2011; Geocadin et al. 2008; Popa-Wagner et al. 2011). To address this discrepancy, the adaptation of current CI models for use in aged animals is necessary. & Eliud Enrique Villarreal-Silva eliud1511@gmail.com 1 Department of Pathology, School of Medicine, Universidad Auto ´ noma de Nuevo Leo ´ n, Madero and Dr. Aguirre Pequen ˜o, Mitras Centro, 64460 Monterrey, Nuevo Leo ´n, Mexico 2 Department of Human Anatomy, School of Medicine, Universidad Auto ´noma de Nuevo Leo ´n, Madero and Dr. Aguirre Pequen ˜o, Mitras Centro, 64460 Monterrey, Nuevo Leo ´n, Mexico 3 Department of Histology, School of Medicine, Universidad Auto ´ noma de Nuevo Leo ´ n, Madero and Dr. Aguirre Pequen ˜o, Mitras Centro, 64460 Monterrey, Nuevo Leo ´n, Mexico 4 Department of Anatomy and Cell Biology, School of Medicine, Indiana University, Van Nuys Medical Science Building 635 Barnhill Drive, MS 507, 46202 Indianapolis, IN, USA 5 Neurosurgery Service, School of Medicine, Universidad Auto ´ noma de Nuevo Leo ´ n, Madero and Dr. Aguirre Pequen ˜o, Mitras Centro, 64460 Monterrey, Nuevo Leo ´n, Mexico 123 Anat Sci Int (2016) 91:226–237 DOI 10.1007/s12565-015-0286-x