Pathophysiology and Treatment of Memory Dysfunction After Traumatic Brain Injury

Abstract

Memory is fundamental to everyday life, and cognitive impairments resulting from traumatic brain injury (TBI) have devastating effects on TBI survivors. A contributing component to memory impairments caused by TBI are alterations in the neural circuits associated with memory function. In this review, we aim to bring together experimental findings that characterize behavioral memory deficits and the underlying pathophysiology of memory-involved circuits after TBI. While there is little doubt that TBI causes memory and cognitive dysfunction, it is difficult to conclude which memory phase i.e., encoding, maintenance or retrieval is specifically altered by TBI. This is most likely due to variation in behavioral protocols and experimental models. Additionally we review a selection of experimental treatments that hold translational potential to mitigate memory dysfunction following injury.

RhoA-ROCK Inhibition Reverses Synaptic Remodeling and Motor and Cognitive Deficits Caused by Traumatic Brain Injury

“…Both contextual fear memory and contextual fear discrimination (i.e. the ability to discriminate between a fearful and a non-fearful environment) depend on the hippocampus, which encodes contextual information, mediates memory formation, and is frequently damaged following TBI 41 , 42 . To determine how TBI impacts contextual fear memory and context discrimination and whether blocking neuronal RhoA signaling reverses these effects, we performed control surgeries (anesthesia and incision) or CCI surgeries on adult RhoA fl/fl and RhoA CKO mice and then subjected them to contextual fear conditioning nine days later.…”

CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury

“…Both produce a region of maximal damage and reduced neuronal responsiveness. In addition to direct motor impairments, TBI also damages hippocampal circuits and produces prominent learning and memory deficits (Paterno et al, 2017). We tested if learning impairments resulting from TBI can be improved through knockdown of CCR5 in CA1 and CA3 hippocampal circuits.…”

Neurodegeneration exposes firing rate dependent effects on oscillation dynamics in computational neural networks

“…Previous work indicates the importance of GABAergic inhibition for developing oscillatory rhythms in cortical circuits [85]. Other studies established that TBI alters E/I balance across different brain regions as well as via various injury modalities and severities [86][87][88][89][90]. E/I balance could shift due to selective vulnerability of interneuron subpopulations or due to changes in excitatory synaptic transmission.…”