Amy Dave

Background: Traumatic brain injury (TBI) is a major public health concern affecting approximately 60 million people annually with the potential for long-term neurological and cognitive impairments. Among the brain regions most affected is the hippocampus, a structure essential for memory, learning, and emotions. Recent studies suggest that TBI cause complex region-specific changes in hippocampal neurogenesis, inflammation, and cell fate determination. However, a comprehensive understanding of the underlying molecular dynamics and cellular processes within specific hippocampal subregions following injury remains limited. Clarifying these mechanisms is necessary for developing therapeutic strategies aimed at enhancing neural repair and function post TBI. This literature review investigates how TBI affects hippocampal subregion responses to elucidate the processes that may promote or hinder brain recovery.

Methods:  Literature was identified through searches of PubMed and Google Scholar using the keywords: “traumatic brain injury,” “hippocampus,” “neurogenesis,” “neural stem cells,” “biomaterials,” “neural tissue regeneration.” Studies selected were published between 2021–2024 and used rodent models to explore cellular or molecular outcomes in the hippocampus post-TBI.s

Results: Multiple studies demonstrated that TBI changes the neurogenic environment of the hippocampus. Clark et al. (2021) showed time-specific increases in cell proliferation and neuroblast presence in the dentate gyrus (DG) following mild TBI, with sustained survival of newly formed cells. Bielefeld et al. (2024) showed that TBI shifts neural stem cell fate toward neurogenesis at the expense of astrogliogenesis and alters the spatial distribution of neural progenitors within the DG. Maity et al. (2024) identified differentially expressed proteins (e.g., GFAP, MUG-1) associated with disrupted plasticity and neurogenesis, indicating how different regions of the hippocampus respond differently at the protein level post TBI. Tanikawa et al. (2023) proposed electrically charged hydrogels that scaffold NSCs and promote neuronal differentiation within TBI lesions, allowing neural networks to be rebuilt at the injury site.

Conclusions: TBI induces a complex set of molecular and cellular changes in the hippocampus that vary by time and subregion. Enhanced neurogenesis and subregion-specific protein shifts suggest the brain’s own attempts at repair, while emerging biomaterials offer therapeutic avenues to support that process. These findings emphasize the importance of targeted therapies tailored to specific stages and regions of TBI. Future studies should explore how different injury severities and timelines impact hippocampal repair to ultimately translate these findings into therapies that ensure neurons integrate functionally into existing circuits.

Works Cited

1. Bielefeld P, Martirosyan A, Martín-Suárez S, et al. Traumatic brain injury promotes neurogenesis at the cost of astrogliogenesis in the adult hippocampus of male mice. Nat Commun. 2024;15(1). doi:10.1038/s41467-024-49299-6
2. Clark LR, Yun S, Acquah NK, et al. Mild Traumatic Brain Injury Induces Transient, Sequential Increases in Proliferation, Neuroblasts/Immature Neurons, and Cell Survival: A Time Course Study in the Male Mouse Dentate Gyrus. Front Neurosci. 2021;14. doi:10.3389/fnins.2020.612749