Prophylactic Zinc Administration Combined with Swimming Exercise Prevents Cognitive-Emotional Disturbances and Tissue Injury following a Transient Hypoxic-Ischemic Insult in the Rat

Abstract

Exercise performance and zinc administration individually yield a protective effect on various neurodegenerative models, including ischemic brain injury. Therefore, this work was aimed at evaluating the combined effect of subacute prophylactic zinc administration and swimming exercise in a transient cerebral ischemia model. The prophylactic zinc administration (2.5 mg/kg of body weight) was provided every 24 h for four days before a 30 min common carotid artery occlusion (CCAO), and 24 h after reperfusion, the rats were subjected to swimming exercise in the Morris Water Maze (MWM). Learning was evaluated daily for five days, and memory on day 12 postreperfusion; anxiety or depression-like behavior was measured by the elevated plus maze and the motor activity by open-field test. Nitrites, lipid peroxidation, and the activity of superoxide dismutase (SOD) and catalase (CAT) were assessed in the temporoparietal cortex and hippocampus. The three nitric oxide (NO) synthase isoforms, chemokines, and their receptor levels were measured by ELISA. Nissl staining evaluated hippocampus cytoarchitecture and Iba-1 immunohistochemistry activated the microglia. Swimming exercise alone could not prevent ischemic damage but, combined with prophylactic zinc administration, reversed the cognitive deficit, decreased NOS and chemokine levels, prevented tissue damage, and increased Iba-1 (+) cell number. These results suggest that the subacute prophylactic zinc administration combined with swimming exercise, but not the individual treatment, prevents the ischemic damage on day 12 postreperfusion in the transient ischemia model.

Physical exercise regulates microglia in health and disease

“…Furthermore, a transgenerational study selecting for low capacity and high-capacity runners found male low-capacity runners had more severe ICH-induced brain injury and greater numbers of major histocompatibility complex class 2 1a (OX-6) positive microglia cells, demonstrating transgenerational regulation of microglia phenotype in a stroke model ( He et al, 2013 ). Both treadmill and swimming exercise have been found to regulate microglial numbers in different brain regions, such as the hypothalamus, hippocampus, basal ganglia, as well as in peri-infarcted and peri-hematoma zones ( Kinoshita et al, 2021 ; Xia et al, 2021 ; Aguilar-Peralta et al, 2022 ; Li et al, 2022 ). However, a single study by Svensson et al reported no impact of exercise on hippocampal microglial number or phenotype in a cerebral ischemic stroke model ( Svensson et al, 2016 ).…”

Dietary zinc protects against methotrexate-induced neurotoxicity in rats via modulation of oxidative stress, inflammation and neuronal energy metabolism

“…The amygdala and hippocampus have the highest concentration of zinc while the brain's extracellular fluid has the lowest concentration [24][25][26]. The neuroprotective effects of zinc have also been reported severally [27][28][29][30]. While there have been reports of the ameliorative potential of zinc in methotrexate induced intestinal damage [31,32].…”