Long intervals between repetitive concussions reduce risk of cognitive impairment and limit microglial activation, astrogliosis, and tauopathy in adolescent rats

TL;DR

This study shows that waiting longer between concussions in adolescent rats reduces cognitive problems and brain inflammation.

Contribution

The study reveals that increasing the time between concussions limits cognitive impairment and pathological brain changes in adolescent rats.

Findings

Rats with daily concussions showed cognitive impairment, while others did not.

Daily concussions caused microglial activation, astrogliosis, and tau accumulation in specific brain regions.

Longer intervals between concussions reduced pathological changes and cognitive risks.

Abstract

Although previous studies have demonstrated the effects of concussions do not accumulate as the time interval between injuries increases, little is known about the relationship between this interval and the effects of repetitive concussions. The objective of this study is to explore the relationship between the time interval and changes in behavior and histology following repetitive concussions. Male adolescent rats received concussions by weight drop and were randomly assigned to one of five experimental groups, receiving concussions three times either daily, every other day, once per week, once every 2 weeks, or receiving sham procedures. Only rats that received daily concussions exhibited cognitive impairment, while the other groups did not. No groups showed motor or anxiety-like impairments. Histological analysis revealed accumulation of microglia, as well as astrogliosis, in the prefrontal cortex, corpus callosum, dentate gyrus, and cornu Ammonis 1 region of the hippocampus in rats subjected to daily concussions. Accumulation of phosphorylated tau was also observed in the prefrontal cortex and cornu Ammonis 1. Longer intervals between concussions may reduce the risk of cognitive impairment and limit microglial activation, astrogliosis, and phosphorylated tau accumulation. These findings may help guide decisions on the appropriate timing for return to play in humans.

The online version contains supplementary material available at 10.1038/s41598-025-24376-y.

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