Astrocyte inhibition impacts metaplasticity in the hippocampal CA1 area following traumatic brain injury.

Traumatic Brain Injury (TBI) is an important contributing factor to cognitive impairment, frequently linked to disturbances in synaptic plasticity and metaplasticity. Astrocytes, as essential regulators of synaptic function, are crucial for sustaining brain circuit activity in both normal and pathological states. Post-TBI, astrocytes reveal reactive alterations that manifest both advantageous and harmful impacts on synaptic plasticity and cognitive performance. This study examines the involvement of astrocytes in traumatic brain injury-induced synaptic dysfunction in the hippocampal CA1 area, seeking to elucidate processes that connect astrocyte reactivity to synaptic transmission and plasticity which might provide insights into cognitive deficits subsequent to TBI and guide prospective therapy strategies. Following the establishment of a traumatic brain injury model via the controlled cortical impact (CCI) method in male Wistar rats, both short-term and long-term synaptic plasticity were examined through field potential recordings. Our findings indicated that TBI significantly diminished baseline synaptic responses (P < 0.05, two-way ANOVA) and reduced LTP (P < 0.001, unpaired t-test) while enhancing LTD in the hippocampus CA1 area (P < 0.01, unpaired t-test). Astrocytic inhibition by Fluorocitrate (FC) intensified LTP deficits (P < 0.01, two-way ANOVA) and prevented LTD augmentation (P < 0.01, two-way ANOVA) in TBI rats. In sham animals, FC had no significant effect on baseline synaptic responses or paired-pulse ratios. These findings emphasize the dual function of reactive astrocytes in synaptic plasticity post-TBI, wherein astrocyte malfunction leads to maladaptive plasticity.