Delayed TBI-Induced Neuronal Death in the Ipsilateral Hippocampus and Behavioral Deficits in Rats: Influence of Corticosterone-Dependent Survivorship Bias?

• Published in: International journal of molecular sciences Vol. 24; no. 5; p. 4542
• Main Authors: Komoltsev, Ilia, Shalneva, Daria, Kostyunina, Olga, Volkova, Aleksandra, Frankevich, Stepan, Shirobokova, Natalia, Belikova, Anastasia, Balan, Sofia, Chizhova, Olesya, Salyp, Olga, Bashkatova, Daria, Kostrukov, Pavel, Soloveva, Aleksandra, Novikova, Margarita, Gulyaeva, Natalia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-02-2023; MDPI
• Subjects: Accuracy; Animal cognition; Animals; Bias; Brain; Brain damage; Brain Injuries, Traumatic - pathology; Corticosterone; Dentate gyrus; Hippocampus; Hippocampus - pathology; Injuries; Male; Maze learning; Maze Learning - physiology; Memory; Memory Disorders - pathology; Memory tasks; Morphology; Mortality; Neurodegeneration; neuroinflammation; Neurons; Pattern recognition; Percussion; Rats; Rats, Sprague-Dawley; Reversal learning; Spatial analysis; Spatial memory; Survival; Survivorship; Trauma; Traumatic brain injury; Germany; Romania; memory; hippocampus; neuroinflammation; neurodegeneration; traumatic brain injury; survivorship bias; corticosterone; microglia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24054542

Acute and chronic corticosterone (CS) elevations after traumatic brain injury (TBI) may be involved in distant hippocampal damage and the development of late posttraumatic behavioral pathology. CS-dependent behavioral and morphological changes were studied 3 months after TBI induced by lateral fluid percussion in 51 male Sprague-Dawley rats. CS was measured in the background 3 and 7 days and 1, 2 and 3 months after TBI. Tests including open field, elevated plus maze, object location, new object recognition tests (NORT) and Barnes maze with reversal learning were used to assess behavioral changes in acute and late TBI periods. The elevation of CS on day 3 after TBI was accompanied by early CS-dependent objective memory impairments detected in NORT. Blood CS levels > 860 nmol/L predicted delayed mortality with an accuracy of 0.947. Ipsilateral neuronal loss in the hippocampal dentate gyrus, microgliosis in the contralateral dentate gyrus and bilateral thinning of hippocampal cell layers as well as delayed spatial memory deficits in the Barnes maze were revealed 3 months after TBI. Because only animals with moderate but not severe posttraumatic CS elevation survived, we suggest that moderate late posttraumatic morphological and behavioral deficits may be at least partially masked by CS-dependent survivorship bias.