Solid-state zinc ion sensor is developed with high enough resolution and reproducibility for the potential application in brain injury monitoring. An optical diffuser is incorporated into the zinc ion sensor based on optical fiber and hydrogel doped with the fluorescent zinc ion probe molecule meso-2,6-Dichlorophenyltripyrrinone (TPN-Cl). The diffuser transforms the high-peak-intensity excitation light near the fiber end into a broad light with moderate local intensity to reduce the degradation of the probe molecule. Reversible detection can be reached for 1, 2, and 5 μM (10 Molar), with slopes 0.3, 0.6, and 0.8 respectively. This is the pathophysiological concentration range after brain injury. The sensor is applied to neuron-glial cultures and macrophage under the stimulation of lipopolysaccharide (LPS), KCl and oxygen/glucose deprivation (OGD) that reflect inflammation, depolarization and ischemia respectively, mimicking events after brain injury. The zinc ion level is raised to 4-5 μM after LPS treatment, and then reduced to <3 μM after the co-treatment with the herbal drug silymarin. The results suggest the conditions of the neural cells under stress can be monitored.Copyright © 2020. Published by Elsevier B.V.