GTPase RhoB: An early predictor of neuronal death after transient focal ischemia in mice

Applying the recently developed DNA array technique to a murine stroke mode l, we found that the gene coding for RhoB, a member of the family of GTPase s that regulate a variety of signal transduction pathways, is upregulated i n ischemia-damaged neurons. RhoB immunoreactivity precedes DNA single-stran d breaks and heralds the evolving infarct, making it an early predictor of neuronal death. Expression of RhoB colocalized with drastic rearrangement o f the actin cytoarchitecture indicates a role for Rho in postischemic morph ological changes. Apoptosis in a murine hippocampal cell line was also asso ciated with an early increase in RhoB protein. Activation of caspase-3, a c rucial step in apoptosis, could be inhibited by cytochalasin D, a substance that counteracts the actin-modulating activity of Rho GTPases, indicating that Rho proteins may have impact on injury-initiated neuronal signal trans duction. Our findings make Rho GTPases potential targets for the developmen t of drugs aimed at limiting neuronal death following brain damage.