Ryanodex Reduces Persistent Hippocampal Effects of Single Mild Traumatic Brain Injury in Rats

This is the authors' abstract. We don't add key points for this paper.

Traumatic brain injury (TBI) affects millions of individuals annually, with a 53% increase in emergency visits since 2006. Despite its prevalence, no FDA-approved treatments exist to mitigate brain damage or promote recovery. While repeated TBI is widely studied, even a single impact can cause persistent neurological changes, likely mediated by Ca 2+ dysregulation via effects on ryanodine receptors. In a rat model of mild TBI, using a single closed-head controlled cortical impact, we observed no changes in the levels of hippocampal glial fibrillary acidic protein and phosphorylated tau—both markers of cellular damage. However, mild TBI (mTBI) significantly enhanced synaptic transmission at hippocampal CA3-CA1 synapses and increased CA1 pyramidal cell excitability for at least 30 days—effects that were significantly attenuated by acute and subacute injection of Ryanodex, a concentrated nanocrystalline formulation of the ryanodine receptor allosteric modulator dantrolene. Ryanodex may, therefore, offer a promising intervention to reduce persistent hippocampal dysfunction following mTBI, with potential clinical applications for acute TBI treatment.