Changes in the Brain after Intracerebral Implantation of a Lead Pellet in the Rat

Abstract

In gunshot wounds to the head, the bullet containing neurotoxic lead may remain in the brain after trauma, and brain damage is therefore anticipated. We developed an animal model incorporating a lead ball implanted in the brain, or a glass ball as a control, and analyzed histological and biochemical changes in the brain for 28 days after surgery. The concentration of lead in the brain increased with time after implantation of the lead ball, while lead was not detected in brains implanted with a glass ball. A number of changes were noted following implantation of the lead ball. The number of neutrophils increased significantly at 7–28 days, while the number of macrophages also increased significantly with time. The number of neurons was significantly decreased by 28 days, and apoptotic cells were identified at 14–28 days. Expression of genes encoding N-methyl-d-aspartate receptors, which are related to cognitive function and help regulate apoptosis, was significantly suppressed at 7–21 days after implantation. Expression of metallothionein protein increased significantly with time. Metallothionein detoxifies lead and its overexpression is a known method of protection against lead neurotoxicity. These findings indicate that intracerebral lead induces neuronal degeneration that is attributable in part to the inflammation and apoptosis caused by leached lead. Although the severity of the brain damage primarily depends on the destructive effect of the moving bullet, the results of this study indicate that lead leaching from the residual bullet also damages the brain.