  Citation: Rizwana, N.; Agarwal, V.; Nune, M. Antioxidant for Neurological Diseases and Neurotrauma and Bioengineering Approaches. Antioxidants 2022, 11, 72. https://doi.org/10.3390/ antiox11010072 Academic Editors: Alessandra Napolitano, Maria Cristina Albertini and Seeram Ramakrishna Received: 23 October 2021 Accepted: 20 December 2021 Published: 29 December 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). antioxidants Review Antioxidant for Neurological Diseases and Neurotrauma and Bioengineering Approaches Nasera Rizwana 1 , Vipul Agarwal 2, * and Manasa Nune 1, * 1 Manipal Institute of Regenerative Medicine (MIRM), Bengaluru, Manipal Academy of Higher Education (MAHE), Manipal 576104, India; nasera.rizwana@learner.manipal.edu 2 Cluster for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia * Correspondence: agarwalvipul84@gmail.com (V.A.); manasa.nune@manipal.edu (M.N.) Abstract: Antioxidants are a class of molecules with an innate affinity to neutralize reactive oxygen species (ROS), which are known to cause oxidative stress. Oxidative stress has been associated with a wide range of diseases mediated by physiological damage to the cells. ROS play both beneficial and detrimental roles in human physiology depending on their overall concentration. ROS are an inevitable byproduct of the normal functioning of cells, which are produced as a result of the mitochondrial respiration process. Since the establishment of the detrimental effect of oxidative stress in neurological disorders and neurotrauma, there has been growing interest in exploring antioxidants to rescue remaining or surviving cells and reverse the neurological damage. In this review, we present the survey of different antioxidants studied in neurological applications including neurotrauma. We also delve into bioengineering approaches developed to deliver antioxidants to improve their cellular uptake in neurological applications. Keywords: antioxidants; oxidative stress; neurotrauma; neuroregeneration; bioengineering approaches 1. Introduction Oxidative stress induced by reactive oxygen species (ROS) is inevitably produced from normal cellular metabolism through mitochondrial respiration and a family of membrane- bound NADPH oxidases (NOXs). ROS are broadly divided into free radicals (molecules with unpaired electrons) and non-radical species. Physiologically, three main ROS types are superoxide anion (O 2 − ), hydroxyl radical (·OH), and hydrogen peroxide (H 2 O 2 )[1]. ROS play an important role in both physiological cell functioning at low to moderate concentra- tions by oxidizing different collocated proteins to activate multiple biochemical pathways associated with cell viability, proliferation, differentiation and metabolic adaptation [2]. However, at high concentrations, ROS are toxic and cause oxidation-induced damage to the pivotal cell components including lipids, proteins and DNA leading to cell cycle arrest and cell death [3–7]. There is growing evidence showcasing that the excess oxidative stress cause different pathological diseases including cancer, atherosclerosis, neurological disor- ders, cardiovascular stress (hypertension, ischemia, reperfusion), diabetes mellitus, chronic inflammation, acute respiratory distress syndrome, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and asthma [8–10]. For example, atherosclerosis is caused by ROS-mediated oxidation of the lipids in low-density lipoprotein (LDL) called lipid peroxidation [11]. In cancer, ROS can promote cancer by introducing conducive genetic mutations by oxidizing specific intracellular chemical moieties and activating biochemical pathways that promote growth and neoplastic transformation [12]. Cancer cells survive high ROS concentrations by preserving the intrinsic concentrations of reduced glutathione and thioredoxin, which allows cells to activate proximal signaling pathways necessary for Antioxidants 2022, 11, 72. https://doi.org/10.3390/antiox11010072 https://www.mdpi.com/journal/antioxidants