The biochemical mechanisms of explosive blast-induced traumatic brain injury and the subsequent long-term neurobehavioral abnormalities are still not completely understood. We studied the biochemical mechanism of blast traumatic brain injury using our recently reported in-vitro model system with a shock tube. Primary blast exposure of in-vitro models leads to neurobiological changes in an overpressure dose-dependent and time-dependent manner. Lactate dehydrogenase was released significantly into the extracellular medium without cell death after blast exposure, indicating compromised cell membrane integrity. We further explored the integrity of cell membrane after blast exposure by fluorescent dye uptake/release techniques in SH-SY5Y human neuroblastoma cells. Our data indicate that blast exposure leads to an overpressure-dependent transient increase in the release of preloaded calcein AM into the culture medium with proportional intracellular decrease. Uptake of an extracellular nucleic acid-binding dye TO-PRO-3 iodide was also increased significantly after blast exposure, indicating that the increased molecular transport is bidirectional and nuclear membrane integrity is also affected by blast exposure. These results suggest that blast exposure perturbs the integrity of the neuronal cell membrane, leading to increased bidirectional transport of molecules--a potential mechanism that can lead to traumatic brain injury.