Overload of intracellular
calcium ([Ca(2+)](i)) following
traumatic brain injury (TBI) has been implicated in the pathogenesis of neuronal injury and death. Voltage-gated
calcium channels (VGCCs) provide one of the major sources of Ca(2+) entry into cells. Therefore, the potential neuroprotective activity of
SNX-185, a specific N-type VGCC blocker, was tested in rats using the lateral fluid percussion (LFP) model of TBI.
SNX-185 (50, 100, or 200 pmol) or vehicle was injected 5 min after injury into the CA2-3 subregion of the hippocampus ipsilateral to TBI. Acute neuronal degeneration was visualized in brain sections 24 h postinjury using the histofluorescent marker
Fluoro-Jade (FJ), and the number of surviving neurons in the CA2-3 subregion of the hippocampus 42 days after injury was determined stereologically. Behavioral outcome after TBI and
drug treatment was assessed in the beam walk test and Morris water maze. Direct injection of
SNX-185 into the CA2-3 region of the hippocampus reduced neuronal injury 24 h after TBI and increased neuronal survival at 42 days at each of the three
drug concentrations. Behavioral outcome in both the beam walk and Morris water maze were also improved by
SNX-185, with 100 and 200 pmol, but not 50 pmol
SNX-185 providing neuroprotection. These data support previous studies demonstrating substantial neuroprotection after TBI by treatment with N-type VGCC blockers.