The release of pro-inflammatory cytokines and growth inhibitory proteins after a SCI results in enhanced signaling of the protein Rho. When Rho is activated, axon regrowth is inhibited. Cethrin®specifically inactivates Rho and therefore enables axons to regrow. In addition, Cethrin®has been shown to reduce inflammation by decreasing hematogenous monocytes, reducing glial scar formation and augmenting neuron remyelination (McKerracher & Guertin, 2013). Unlike most acute spinal cord drugs reviewed so far that have been delivered intravenously, Cethrin®is applied topically to the spinal cord during the time of surgery.
Another emerging neuroprotective drug is minocycline, a broad spectrum antibiotic. Minocycline is able to cross the blood-brain barrier and exhibits anti-inflammatory and anti-excitatory properties (Baptiste & Fehlings, 2006). Studies investigating SCI in animal models have suggested that this drug inhibits microglial proliferation, reduces cellular apoptosis and neutralizes free radicals (Yong et al. 2004). These properties have made it a promising candidate for neurological disorders such as Parkinson’s disease, stroke, and multiple sclerosis in addition to SCI (Casha et al. 2012).
During secondary injury, an influx of sodium enters nerve cells and instigates an osmotic response where the neurons begin to swell to dangerous levels. In response, calcium rushes into the cell and triggers an amplified sodium excretion from the cell. Subsequently, the high intracellular concentration of calcium results in glutamate release and therefore excitotoxicity (Wilson & Fehlings, 2014). Riluzole acts to block these sodium channels, thus preventing excitotoxicity. Animal studies have found spinal cord injured rats that received riluzole to have improved motor function, more brain stem neurons and a smaller lesion size after 6 weeks compared to rats that received different sodium channel blockers or a placebo (Schwartz & Fehlings, 2001). Earlier human trials with riluzole have led to its approval by the Food and Drug Administrationin the US for the treatment of amyotrophic lateral sclerosis (Wilson & Fehlings, 2014).