Posttraumatic learning deficits correlate with initial trauma severity and chronic cellular reactions after closed head injury in male mice.

Abstract

Traumatic brain injury (TBI) is often associated with sustained attention and memory deficits. As persisting neuroinflammation and neurodegeneration may contribute to posttraumatic psychomotor dysfunction, we studied the relationship of brain cellular reactions three months after a weight-drop closed head injury in male mice with posttraumatic learning and memory using automated home-cage monitoring of socially housed mice in IntelliCages as well as tests for locomotor activity, anxiety and forepaw fine motor skills. One month after TBI, deficits in place learning and cognitive flexibility in reverse learning were clearly detectable in IntelliCages and these memory deficits correlated with the initial trauma severity on the functional neuroscore. While sucrose preference or its extinction were not influenced by TBI, traumatized mice performed significantly worse in a complex episodic memory learning task. In consecutive locomotor and forepaw skilled use tests, posttraumatic hyperactivity and impairment of contralateral paw use were evident. Analysis of cellular reactions to TBI three months after injury in selected defined regions of interest in the immediate lesion, ipsi- and contralateral frontoparietal cortex and hippocampus revealed a persistent microgliosis and astrogliosis which were accompanied by iron-containing macrophages and myelin degradation in the lesion area as well as with axonal damage in the neighboring cortical regions. Microglial and astroglial reactions in cortex showed a positive correlation with the initial trauma severity and a negative correlation with the spatial and episodic memory indicating a role of brain inflammatory reactions in posttraumatic memory deficits.

• Authors: Simon Lopez-Caperuchipi, Lydia Kürzinger, Sarah Hopp-Krämer, Christiane Albert-Weißenberger, Mila M Paul, Anna-Leena Sirén, Christian Stetter
• Journal: Experimental neurology (Exp Neurol) Vol. 341 Pg. 113721 (07 2021) ISSN: 1090-2430 [Electronic] United States
• PMID: 33852877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Topics

• Animals
• Brain Injuries, Traumatic (complications, pathology, physiopathology)
• Gliosis (etiology, pathology, physiopathology)
• Locomotion (physiology)
• Male
• Maze Learning (physiology)
• Mice
• Mice, Inbred C57BL
• Severity of Illness Index
• Spatial Learning (physiology)