Repetitive Traumatic Brain Injury Causes Neuroinflammation before Tau Pathology in Adolescent P301S Mice

Abstract

Repetitive closed head injury (rCHI) is commonly encountered in young athletes engaged in contact and collision sports. Traumatic brain injury (TBI) including rCHI has been reported to be an important risk factor for several tauopathies in studies of adult humans and animals. However, the link between rCHI and the progression of tau pathology in adolescents remains to be elucidated. We evaluated whether rCHI can trigger the initial acceleration of pathological tau in adolescent mice and impact the long-term outcomes post-injury. To this end, we subjected adolescent transgenic mice expressing the P301S tau mutation to mild rCHI and assessed tau hyperphosphorylation, tangle formation, markers of neuroinflammation, and behavioral deficits at 40 days post rCHI. We report that rCHI did not accelerate tau pathology and did not worsen behavioral outcomes compared to control mice. However, rCHI induced cortical and hippocampal microgliosis and corpus callosum astrocytosis in P301S mice by 40 days post-injury. In contrast, we did not find significant microgliosis or astrocytosis after rCHI in age-matched WT mice or sham-injured P301S mice. Our data suggest that neuroinflammation precedes the development of Tau pathology in this rCHI model of adolescent repetitive mild TBI.

Neuronal tau pathology worsens late-phase white matter degeneration after traumatic brain injury in transgenic mice

“…11 ). However, in agreement with our post-injury results, repetitive closed head injury increased the microglial response in PS19 mice [ 42 ]. The PS19 prion promoter may be advantageous in the context of tau spreading, which was accelerated after a moderate-severe penetrating TBI, and resulted in learning and memory impairment [ 22 ].…”

Post-stroke cognitive impairment: exploring molecular mechanisms and omics biomarkers for early identification and intervention

“…Existing research have primarily demonstrated a statistical link rather than a definitive causal relationship between specific mechanisms and the disease. Studies discovered that the accumulation of amyloid β might trigger an inflammatory reaction, and subsequent processes resulting from these inflammatory changes may be the underlying cause of the disease in PSCI ( Lalancette-Hébert et al, 2012 ; Ott et al, 2018 ; Izzy et al, 2021 ). Likewise, oxidative stress can impact the integrity of neurons and the expression of genes, which in turn affects cognitive performance by causing changes in the structure of hippocampal dendrites ( Chi et al, 2023 ).…”

The Influence of Virus Infection on Microglia and Accelerated Brain Aging

“…Microglia are essential to the healthy brain, as they contribute to many brain functions and help sustain the physiological brain structure [ 83 , 214 , 215 ]. Belonging to the innate immune system of the brain, microglia contribute to an immune response against any brain-invading agent [ 35 , 216 , 217 ], as well as following traumatic and neurovascular brain damage [ 218 , 219 , 220 ]. They help with resolving tissue damage and support regeneration and restauration of structure and function [ 74 ].…”