Dendritic Spines and Pre-Synaptic Boutons Are Stable Despite Local Deep Hypothermic Challenge and Re-Warming In Vivo

BACKGROUND AND PURPOSE Deep hypothermia to 20°C is used clinically for major pediatric and adult surgical procedures. In particular, it is used in the "standstill operation" where blood flow is stopped for up to 30 min. Patients recovering from these procedures can exhibit neurological deficits. Such deficits could arise from changes to dendritic spines and plasticity-induced changes in network function as a result of cooling and/or re-warming. In the brain, each dendritic spine represents a single excitatory synapse and their number can be reflective of injury or plasticity-induced changes in network function. This research sought to determine whether deep hypothermia and re-warming have detrimental effects on synaptic stability and network function. METHODS In vivo 2-photon (2-P) imaging in green/yellow fluorescent protein (GFP/YFP)-expressing transgenic mice was performed to determine whether 4 hours of deep hypothermia and 2 hours of re-warming can have relatively covert effects on dendritic spine and presynaptic bouton stability. At the same time, electroencephalographic (EEG) activity was recorded to evaluate network function during deep hypothermia and re-warming. RESULTS We report that deep hypothermia and subsequent re-warming did not change the stability of dendritic spines or presynaptic boutons in mouse somatosensory cortex measured over 8 hours. As expected, deep hypothermia attenuated ongoing EEG activity over 0.1-80 Hz frequencies. The effects on EEG activity were fully reversible following re-warming. CONCLUSION These results are consistent with deep hypothermia being a safe treatment which could be applied clinically to those undergoing major elective surgical procedures.