A Mouse Model of Neurodegeneration Induced by Blade Penetrating Stab Wound to the Hippocampus

SIMPLE SUMMARY: To date, various animal models of traumatic brain injury (TBI) have been developed to investigate the cellular and molecular networks underlying the pathogenesis of neurodegeneration, and to examine the safeness and therapeutic efficacy of drugs. However, the commonly used animal TBI models usually have the weaknesses of low reproducibility and high mortality rates. In the present study, we created a mouse model of cognitive deficits induced by a blade penetrating stab wound to the hippocampus (HBSI). This model will contribute a better understanding of neurodegeneration and accelerate the translation of preclinical research to clinical applications. ABSTRACT: Traumatic brain injury (TBI) is closely associated with the later development of neurodegenerative and psychiatric diseases which are still incurable. Although various animal TBI models have been generated, they usually have weaknesses in standardization, survivability and/or reproducibility. In the present study, we investigated whether applying a blade penetrating stab wound to the hippocampus would create an animal model of cognitive deficits. Open-field, Morris water maze and Barnes maze tests were used to evaluate the animal behaviors. The immunofluorescence staining of NeuN, GFAP, IBA1, and TUNEL was conducted to analyze the changes in neurons, astrocytes, and microglia, as well as cell death. Mice with a hippocampal blade stab injury (HBSI) displayed the activation of microglia and astrocytes, inflammation, neuronal apoptosis, and deficits in spatial learning and memory. These findings suggest that HBSI is an easy approach to generate a reliable in vivo model of TBI to capture hemorrhage, neuroinflammation, reactive gliosis, and neural death, as well as cognitive deficits observed in human patients.