Research Article Mitigated Oxidative Stress and Cognitive Impairments in Transient Global Ischemia using Niosomal Selegiline- NBP delivery Bahareh Jafari, 1 Mahmoud Gharbavi, 2 Yasamin Baghdadchi, 3 Hamidreza Kheiri Manjili, 1,3 Javad Mahmoudi, 4 Iraj Jafari-Anarkoli, 5 Shayan Amiri, 1 and Mir-Jamal Hosseini 1 1 Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran 2 Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 3 Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran 4 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 5 Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Correspondence should be addressed to Mir-Jamal Hosseini; jamal_hossini@yahoo.com Received 9 September 2021; Accepted 26 March 2022; Published 16 April 2022 Academic Editor: Jan Aasly Copyright © 2022 Bahareh Jafari et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Stroke is the most common reason for adult disabilities and the second ground for death worldwide. Our previous study revealed that selegiline serves as an alternative candidate in transient hypoxia-ischemia. However, aggressive and restless behavior was observed in stroke-induced rats receiving 4 mg/kg selegiline. In comparison, 1 mg/kg selegiline could induce negligible therapeutic effects on mitochondrial dysfunction and histopathological changes. Therefore, we designed oral noisome-based selegiline attached to 4-(4-nitrobenzyl) pyridine to improve transient global ischemia by attenuating cognitive impairments, oxidative stress, and histopathological injury. The investigation was performed in transient hypoxia-ischemia-induced rats by oral administration of nanoformulation containing selegiline (0.25-1 mg/kg) for 4 weeks (3 times a week). Novel object recognition (NOR) was considered to evaluate their cognitive dysfunction. Oxidative stress parameters and brain histopathological assessments were determined following the scarification of rats. Outstandingly, our data demonstrated slower selegiline release from niosomes relative to free drug, which was also in a controlled manner. Our data confirmed significant improvement in cognitive behavior in the NOR test, an increase in glutathione level and total antioxidant power, a decline in MDA and protein carbonyl level, as well as a decreased number of dead cells in histopathological assessment after being exposed to (0.5-1 mg/kg) selegiline-NBP nanoformulation. These data manifested that the selegiline-NBP nanoformulation (0.5-1 mg/kg) could significantly reduce oxidative damage, cognitive dysfunction, and histopathological damage compared to transient hypoxia-ischemia rats, which is 20 times lower than the therapeutic dose in humans. Therefore, the proposed nanoformulation would be capable as an alternative candidate without side effects in stroke. 1. Introduction Stroke is a devastating neurological condition, which deteri- orates the quality of life and causes mortality and disability throughout the world [1]. Unfortunately, the resulting bur- den of stroke on society is growing with the increase in its incidence [2, 3]. Few patients are eligible for the immediate restoration of cerebral blood flow by thrombolytic agents since it is effective only in a limited time window after stroke onset and only helps open occluded cerebral vessels [4]. In the ischemic stroke condition, pathological damage is observed following inflammation, oxidative stress, cell death signaling induction, and edema which is correlated to blood- brain barrier (BBB) disruption [5]. Therefore, it is highly Hindawi Behavioural Neurology Volume 2022, Article ID 4825472, 21 pages https://doi.org/10.1155/2022/4825472