2002 Director's Summary Synopsis

CLARIFYING INTRICATE INJURY MECHANISMS
W. Dalton Dietrich, Ph.D. • Robert W. Keane, Ph.D. • John M. Bethea, Ph.D.

During nervous system development, some cells serve their purpose for a short time and are then programed to die. Many studies suggest that apoptosis, this programed cell suicide, is reactivated following SCI and may be the cause of some cell death. To target apoptosis, Miami Project Scientific Director Dr. Dietrich with University of Miami colleague Dr. Keane, evaluated the effectiveness of a caspase inhibitor in animals with SCI. Caspase inhibitors have been effective in some types of experimental CNS injury, but few studies have tested them in traumatic SCI. The results indicate that the caspase inhibitor did not inhibit apoptosis and raise questions about their use in traumatic SCI.

In addition to apoptosis, researchers suspect that intricate inflammatory processes also contribute to immediate and delayed damage. Spinal cord injury sets off a strong immune response within the spinal cord. Immune cells within the spinal cord become activated and cells from outside the spinal cord enter the tissue causing additional immune response. A protein, RGS7, may have an important effect on the inflammatory process. Dr. Bethea measured RGS7 expression after SCI. He found higher levels of the protein in neurons and in immune cells called macrophages. Future studies will evaluate how treatments to block RGS7 expression affects inflammation. In another study by Dr. Dietrich, he and his colleagues looked at the role of a neuromessenger nitric oxide (NO) in inflammation. In traumatic brain injury and stroke, the presence or absence of nitric oxide can indicate various stages of inflammation. While they measured the level of NO after injury, they also examined the effects of an aminoguanidine treatment to learn its effects on reducing the inflammatory process. The results show that the treatment reduced spinal cord damage and improved function. Studies such as these lead to a clearer understanding of how the nervous system responds to injury and provide basic information for the design of new therapies.

Synopsis Publications

 Ozawa H, Keane RW, Marcillo AE, Diaz PH, Dietrich WD. Therapeutic strategies targeting caspase inhibition following spinal cord injury in rats.  Exp Neurol. 2002 Sep;177(1):306-13.

 Hausmann ON, Hu W-H, Keren-Raifman T, Witherow DS, Wang Q, Levay K, Frydel B, Slepak VZ, Bethea JR (2002) Spinal cord injury induces expression of RGS7 in microglia/macrophages in rats. Eur J Neurosci 15:602-612.

 Chatzipanteli K, Garcia, R, Marcillo AE, Loor KE, Kraydieh S, Dietrich WD (2002) Temporal and segmental distribution of constitutive and inducible nitric oxide synthases after traumatic spinal cord injury: Effect of aminoguanidine treatment. J Neurotrauma 19:639-651.