In-vitro sensing of traumatic brain tissue by electrochemical impedance for diagnosis and therapeutic

Abstract

Traumatic brain injury (TBI) induces neurogenerative disorders affecting severely daily human activities and early diagnosis is a critical requirement for prevention and cure. Here, we induced TBI formation in the Zebra fish, a model organism, by both mechanical (ultrasonic cleaner generated convulsive shock, UGCS) and chemical (pentylenetetrazol, PTZ) methods. The TBI induced cellular and neuronal changes are monitored by measuring the activities of the indicator biomarkers viz., superoxide anion (O2−) and glutamate by electrochemical techniques. For this, the α-lipoic acid (α-LA, LA) functionalized gold-silver (LA-Au/Ag) is used as an electrochemical sensor to diagnose the presence of these markers in physiological phosphate buffer saline (PBS, pH 7.4), 0.1 M KCl solutions and in TBI tissues. While the oxidation of glutamate is observed in the potential window 0.2–0.5 V, the metal mediated oxidation of O2− is observed at the potential window 0.6–1.0 V. The sensor showed good linear ranges for O2− (from 4 to 48 μM with the LOD of 4 μM for the O2− detection) and glutamate (from 20 to 130 μM with the LOD 19 μM). The TBI tissue modified electrode showed lower resistance than the normal brain tissue ((NBT), as control) due to the presence of higher amount of O2− and occurrence of Fenton’s and Heber-Weise’s reactions in the presence of [Fe(CN)6]3−/4−. For theragnostic application, the LA-Au/Ag nanoparticles is delivered into the UGCS and PTZ treated Zebrafish and electrochemical signal changes are monitored by cyclic voltammetry and impedance spectroscopy. Electrochemical data further corroborated with the activities of superoxide dismutase (SOD), Catalase (CAT) and lipid peroxidase (MDA) in parallel. The developed method of electrochemical sensing of TBI may provide alternative for the early TBI diagnosis and therapeutics for the prevention of TBI.