Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Research article Continuous and not continuous 2-week treadmill training enhances the performance in the passive avoidance test in ischemic gerbils Ana Paula Cassiano Silveira a , Takae Tamy Kitabatake a , Vivian Mozol Pantaleo a , Hélio Zangrossi Júnior b , Guilherme Bertolino a , Elaine Caldeira de Oliveira Guirro a , Hugo Celso Dutra de Souza a , João Eduardo de Araujo a, ⁎ a Laboratory of Neuropsychobiology and Motor Behavior, Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System, Ribeirão Preto Medical School of the University of São Paulo (USP),AV. dos Bandeirantes, 3900, Ribeirão Preto (SP), 14049-900, Brazil b Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), AV. dos Bandeirantes, 3900, Ribeirão Preto (SP), 14049-900, Brazil ARTICLE INFO Keywords: Treadmill training Global ischemia Passive avoidance test Shuttle box ABSTRACT This study aims to investigate the frequency and total duration effects of the 2-week treadmill training after experimental ischemic stroke in the passive avoidance test. We performed bilateral occlusion of common ex- ternal carotid arteries, for five minutes, in Mongolian gerbils. The training groups were: continuous training for twelve consecutive days or not continuous training for six non-consecutive days. The groups remained in the treadmill for 15 min, with the speed set at 10 m/min, and the training started 24 h after the stroke. In the Shuttle Box, each animal had ten trials during the Learning Session (LS), which occurred 24 h before the stroke. The Retention Test (RT) occurred 24 h after the stroke and started on the second, third, seventh and twelfth day after LS. After the experiments, the brains were perfused, and coronal sections of the CA1 area of the hippocampus were cut and stained with hematoxylin and eosin. ANOVA on Ranks was used for Behavioral data analysis and morphological data by percentage. Ischemic training groups showed preservation in neuron density in the CA1 area of the hippocampus, when compared to the control groups. Animals subjected to continuous training, showed a higher latency in the RT when compared to ischemic animals in both weeks [(2nd, H = 39.81; P < 0.05), (3rd, H = 38.08; P < 0.05), (7th, H = 44.17; P < 0.05), and (12th, H = 39.55; P < 0.05). Animals in the not continuous training showed higher latency in the RT, in the second week only [(2nd, H = 39.81; P < 0.05), (3rd, H = 38.08; P < 0.05), (7th, H = 44.17; P < 0.05), and (12th, H = 39.55; P < 0.05). These findings suggest that improvement of memory after stroke after treadmill training is depen- dent on the frequency and total duration of training. 1. Introduction Brain ischemia causes disability among adults, since it makes the total functional recovery always a challenge [1,2]. The obstruction of one or more blood vessels that irrigate the brain characterizes the is- chemic strokes [3]. After ischemic stroke, motor, learning, memory and other deficits arise [4] and are due to neuronal death that occurs after necrosis and apoptosis of the areas submitted to ischemia [5]. Physical exercise is widely used in experimental and clinical studies since evidence suggests that it can prevent brain atrophy and improve cognitive performance in healthy subjects and subjects with degen- erative diseases [6]. Physical exercise can prevent neuronal death and thus promote the recovery of lost functions [7]. The parameters such as frequency of exercise, intensity, duration, and specificity are a challenge for proposing a protocol of physical exercises to prevent da- mage or restore the brain function after ischemia [1,2]. In rats, forced treadmill exercise decreases the size of damaged areas compared to sedentary ischemic controls [8,9]. Acute treadmill protocols, with a duration of 5 consecutive days, using a speed of 10meters/min, lasting 15 min beginning 24 h after ischemic lesion, preserves the motor behavior in ischemic Gerbils [10,11]. On the other hand, the earlier onset of exercise might increase the injured area in rats [12]. Among the parameters for the prescription of physical exercise after ischemia, the start time appears to be in agreement. Twenty four hours post-ischemic lesions interventions [13,14] are more effective than those performed after 12 h, 3, and 7 days [15,16] in Gerbils and rats. The mechanisms by which physical activity changes the brain https://doi.org/10.1016/j.neulet.2017.12.012 Received 13 September 2017; Received in revised form 30 October 2017; Accepted 4 December 2017 ⁎ Corresponding author at: Medical School of the University of São Paulo USP AV dos Bandeirantes, 3900 Ribeirão Preto SP 14049 900, Brazil. E-mail address: araujoje@fmrp.usp.br (J.E. de Araujo). Neuroscience Letters 665 (2018) 170–175 Available online 06 December 2017 0304-3940/ © 2017 Elsevier B.V. All rights reserved. T