Neuroprotection with

Members of the Bcl-2 proto-oncogene family have been identified as major modulators of programmed cell death, with Bcl-2 gene products either enhancing or diminishing the likelihood of neuronal survival. This regulation appears to be essential to normal brain development, where programmed cell death may eliminate up to 50% of neurons as a part of selective pruning during formation of neuronal networks.1 In addition to this physiological role, the Bcl-2 family appears to be active in brain pathophysiology, by modulating neuronal survival after injury.2 The Bcl-2 protein has been demonstrated to be neuroprotective, since the presence of Bcl-2 gene inhibits neuronal death from apoptosis.3 In addition, the overexpression of the Bcl-2 gene is associated with enhanced neuronal survival after ischemia.4 Although the neuroprotective effects of the Bcl-2 protein may be substantial, the mechanism of this protection is not clearly understood. However, data suggest that the BH4 region near the N-terminus may be in involved, since deletion of N-terminal region in fibroblasts promotes rather than inhibits cell death.5 Therefore, we examined neuroprotective effects of the peptide sequence Bcl-220-34, which is contained within the N-terminal region. For our study, we utilized the hippocampal slice and monitored the electrophysiological function of CA1 pyramidal neurons subjected to fluid percussion trauma.6 Electrophysiological function was utilized as a marker of neuroprotection, because the preservation of neuronal electrophysiological function is the ultimate goal of neuroprotective efforts. The response of hippocampal CA1 pyramidal neurons to Bcl-220-34 were monitored, because these neurons have been found not to express endogenous Bcl-2 in either a basal state or following hypoxia– ischemia injury.7 In addition, CA1 pyramidal cells show great vulnerability to clinical head trauma8 and hypoxia–ischemia.9 Memory loss is the most frequent deficit seen after head trauma,10 and the CA1 pyramidal neuron population has been found to play a critical role in memory formation.11