Increased levels of axonal calcium have been found after Traumatic Brain injury. Calcium can enter the cell from an extracellular source or be released from intracellular stores. Here, we investigate the importance of intracellular calcium in axonal pathology by chelating intracellular calcium and isolating components of the injury pathway such as membrane damage, calcium influx, mitochondrial injury, and increased oxidative stress. The findings were that chelating intracellular calcium with BAPTA-AM was neuroprotective after increasing membrane permeability with melittin, damaging mitochondria with CCCP, and increasing oxidative stress with TbHp. Chelating intracellular calcium was not neuroprotective after injuring cells by selectively increasing axonal calcium with A23187.