FIGURE 4.

Representation of the biological timeline of the synapse after impact. (A) Thin synapse before an impact. Thin spines are considered a transitory spine phenotype, with the potential to transition in an excitatory synapse. (B) Within minutes after impact, synaptic changes within the hyperacute phase after impact. Membrane ruptures and ionic imbalances promote the hyperexcitability of the synapse, with an influx of Ca²⁺ into the post-synaptic terminal via NMDAr (purple). (C) Further damage to the synapse due to hyperexcitability and sustained release of glutamate from the pre-synaptic terminal is observed several hours after impact. Increased influx of Ca²⁺ into the post-synaptic terminal promotes the further upregulation of NMDAr, as well as upregulating GluR1 subunit of AMPAr (red). Disinhibition of synaptic reconstruction proteins, such as EB3 (green), occurs as restricting proteins become inactivated, promoting excitatory mushroom spine phenotype. Hyperexcitability promotes neurodegenerative pathways via overworked mitochondria and damage to the microtubule cytoskeleton of the neuron. Created with BioRender.com.