Differential genomic expression after in vitro mechanical injury of organotypic brain slice cultures

Traumatic brain injury (TBI) is responsible for approximately 80,000 permanently disabled persons per year, however, there is currently no pharmacological treatment for the head injured patient. The primary mechanical stimulus responsible for TBI occurs in less than a second, but is capable of initiating an extended cellular and molecular sequelae requiring hours or days or years to develop which results in the death of brain cells. A more thorough understanding of these molecular changes, including alterations in gene expression, could suggest new therapies for the TBI patient to either ameliorate detrimental or augment beneficial aspects of the post-traumatic sequelae. A novel in vitro model of TBI was developed to produce a precise and reproducible mechanical injury of long term organotypic brain slice cultures (OBSC) at strains and strain rates thought to be responsible for in vivo TBI. At 24 h after in vitro stretch injury, the expression of BDNF, NGF, and TrkA was increased whereas that of bcl-2, CREB, and GAD₆₅ was decreased. These results imply that apoptosis may play a role in cell death after TBI and suggest new therapies for the patient including infusion of growth factors such as BDNF or NGF