Epilepsy after penetrating brain injury

Brain trauma is a common cause of epilepsy, especially trauma from penetrating injuries (e.g. gun shot
wounds) in which 60% of the injury survivors may develop epilepsy. There are over 3000 surviving veterans
of the recent wars with penetrating brain injuries, and an estimated 11,000 new head wound survivors in the
American civilian population each year, so the potential for epilepsy among this group is significant. Data
also suggest that severe head injury survivors have an increased risk for the later development of dementia.
One of the established risk factors for subsequent epilepsy is the presence of foreign materials, including
metallic fragments (e.g. copper and lead) from bullets. At present very little is known about the
pathophysiology of this form of epilepsy and how the risk factors contribute to the development of the
seizures. Copper and lead are toxic materials that have the potential to cause greater damage over the long
term . We have recently developed a model of penetrating brain injury that has an incidence of epilepsy over
80%, and the presence of copper in the lesion is the critical factor, as the lesion alone has a much lower
incidence of epilepsy. In addition to the epilepsy, these metal fragments also are associated with significant
brain necrosis and volume loss over the 6 months that the animals were followed. This extensive added
damage is not seen in lesioned animals without the added metal. These observations raise a number of
questions about the causes of epilepsy, and they also have implications for the clinical care of the survivors of
these injuries, especially if these metals cause further damage beyond the initial injury. Before we can start
to investigate the many mechanistic questions about the progressive injuries and the development of
epilepsy, we have to focus on two fundamental issues which will set the direction for all subsequent studies
and which may help direct future clinical care. The questions in this project are 1) Is it the duration of the
exposure to the toxic metals that lead to epilepsy? and 2) Is the extent of the damage associated with copper
and lead related to the duration of exposure to the metals? The central hypothesis for this project is The
damage and the epilepsy related to the presence retained toxic metal fragments result from the
duration of exposure to the metals. We will answer these questions with our new model of post traumatic
epilepsy by first creating a penetrating injury in rats, adding to the injury stainless steel (control), lead or
copper and evaluating the animals for the development of epilepsy and the severity of the injury following
predetermined exposures to the two metals. Determining that the severity of damage and the development of
epilepsy are influenced by the length of exposure will have a significant impact on clinical care directed to
reducing the risks for epilepsy and long term functional deterioration. The results will also provide a basis for
more in depth future studies on the mechanisms of this type of acquired focal epilepsy.

Grant Number: 1R21NS130385-01A1
NIH Institute/Center: NIH
Principal Investigator: EDWARD BERTRAM