Sustained Hippocampal Synaptic Pathophysiology Following Single and Repeated Closed-Head Concussive Impacts

Area of Science:

• Neuroscience
• Neurology
• Traumatic Brain Injury Research

Background:

• Traumatic brain injury (TBI), including concussions, is linked to long-term neurological issues affecting memory and behavior.
• Repeated concussions exacerbate symptoms compared to single events, impacting cognition and brain pathology.
• Understanding the persistent effects of concussions on synaptic transmission, plasticity, and calcium signaling is crucial.

Purpose of the Study:

• To compare the persistent effects of single versus repeated concussive impacts on memory encoding mechanisms.
• To investigate alterations in synaptic transmission, plasticity, and cellular Ca2+ signaling post-concussion.
• To assess the development of pathogenic phospho-tau species following concussive injuries.

Main Methods:

• A controlled cortical impact (CCI) model was used in adult male rats to simulate single or repeated concussions.
• Electrophysiological recordings and 2-photon Ca2+ imaging were performed on hippocampal slices 30 days post-injury.
• Immunohistochemistry was used to detect pathogenic phospho-tau species.

Main Results:

• Both single and repeated concussions resulted in hyper-excitable hippocampal synaptic responses.
• Elevated resting Ca2+ levels and voltage-gated Ca2+ signals were observed in concussion groups.
• Pathogenic phospho-tau staining increased progressively with concussion severity and spread beyond the injury site.

Conclusions:

• Concussions induce persistent alterations in hippocampal excitatory synaptic function, potentially via Ca2+ signaling changes.
• These synaptic changes may contribute to long-term cognitive deficits and the histopathology seen in TBI, CTE, and AD.
• The findings highlight the sustained impact of concussions on brain circuitry and the potential for tau pathology development.