The outcome of spinal cord injury depends on the extent of secondary damage produced by a series of cellular and molecular events initiated by the primary trauma. This article reviews the evidence that secondary spinal cord injury involves the apoptotic as well as necrotic death of neurons and glial cells. Also discussed are the major factors that can contribute to cell death, such as glutamatergic excitotoxicity, free radical damage, cytokines, and inflammation. The development of innovative therapeutic strategies to reduce secondary spinal cord injury depends on an increased understanding of secondary injury mechanisms at the molecular and biochemical level. Such therapeutic interventions may include the use of antiapoptotic drugs, free radical scavengers, and anti-inflammatory agents. These could be targeted to block key reactions on cellular and molecular injury cascades, thus reducing secondary tissue damage, minimizing side effects, and improving functional recovery.

We have used immunohistochemistry and immunoblotting to examine the expression of Bid and four other Bcl-2 family proteins (Bcl-2, Bcl-X, Bax and Bak)in the developing and adult murine central nervous system (CNS). Bid protein is widespread in embryonic and postnatal brain, and its expression is maintained at a high level late into the adulthood. Bid is expressedbothinthegermdisc,earlyneuraltube,proliferating stem cells of ventricular zones, and in postmitotic, differentiated neurons of the developing central and peripheral nervous system. As the differentiation proceeds, the neurons express higher levels of Bid than the stem cells of the paraventricular zone. Both in embryonic and postnatal life, Bid protein is present in the most vital regions of brain, such as the limbic system, basal ganglia, mesencephalic tectum, Purkinje cells in cerebellum, and the ventral columns of spinal cord. The p15 cleaved form of Bid was detectable in the brain specimens at fetal stages of development, consistent with caspasemediated activation of this pro-apoptotic Bcl-2 family protein.Among the Bcl-2 family proteins only Bid and Bcl-X L continue to be expressed at high levels in the adult brain.

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