Mild Fluid Percussion Injury Induces Diffuse Axonal Damage and Reactive Synaptic Plasticity in the Mouse Olfactory Bulb.

Despite the regenerative capacity of the olfactory bulb (OB), head trauma causes olfactory disturbances in up to 30% of patients. While models of olfactory nerve transection, olfactory receptor neuron (ORN) ablation, or direct OB impact have been used to examine OB recovery, these models are severe and not ideal for study of OB synaptic repair. We posited that a mild fluid percussion brain injury (mFPI), delivered over mid-dorsal cortex, would produce diffuse OB deafferentation without confounding pathology. Wild type FVB/NJ mice were subjected to mFPI and OB probed for ORN axon degeneration and onset of reactive synaptogenesis. OB extracts revealed 3 d postinjury elevation of calpain-cleaved 150-kDa αII-spectrin, an indicator of axon damage, in tandem with reduced olfactory marker protein (OMP), a protein specific to intact ORN axons. Moreover, mFPI also produced a 3-d peak in GFAP+ astrocyte and IBA1+ microglial reactivity, consistent with postinjury inflammation. OB glomeruli showed disorganized ORN axons, presynaptic degeneration, and glial phagocytosis at 3 and 7 d postinjury, all indicative of deafferentation. At 21 d after mFPI, normal synaptic structure re-emerged along with OMP recovery, supporting ORN afferent reinnervation. Robust 21 d postinjury upregulation of GAP-43 was consistent with the time course of ORN axon sprouting and synapse regeneration reported after more severe olfactory insult. Together, these findings define a cycle of synaptic degeneration and recovery at a site remote to non-contusive brain injury. We show that mFPI models diffuse ORN axon damage, useful for the study of time-dependent reactive synaptogenesis in the deafferented OB.