Blood-brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks.

Repeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood-brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3 days per week for 2 weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2 weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits.

Lipid-laden partially-activated plasmacytoid and CD4(-)CD8α(+) dendritic cells accumulate in tissues in elderly mice.

BACKGROUND: Aging is associated with a decline in lymphocyte function however, little is known about dendritic cell (DC) subsets and aging. Aging is also associated with increasing circulating lipid levels and intracellular lipid accumulation modulates DC function. Whether age-associated increases in lipid levels influence DC biology is unknown. Thus, the effects of aging on DC subsets were assessed in vivo using young adult and elderly C57BL/6 J mice. RESULTS: Major age-related changes included increased CD11c(+) DC numbers in lymph nodes, spleens and livers, but not lungs, and significantly increased proportions of plasmacytoid (pDC) and CD4(-)CD8α(+) DCs in lymph nodes and livers. Other changes included altered pDC activation status (decreased CD40, increased MHC class-I and MHC class-II), increased lipid content in pDCs and CD4(-)CD8α(+) DCs, and increased expression of key mediators of lipid uptake including lipoprotein lipase, scavenger receptors (CD36, CD68 and LRP-1) in most tissues. CONCLUSIONS: Aging is associated with organ-specific numerical changes in DC subsets, and DC activation status, and increased lipid content in pDCs and CD4(-)CD8α(+) DCs. Up-regulation of lipoprotein lipase and scavenger receptors by lipid-rich pDCs and CD4(-)CD8α(+) DCs suggests these molecules contribute to DC lipid accumulation in the elderly. Lipid accumulation and modulated activation in pDCs and CD4(-)CD8α(+) DCs may contribute to the declining responses to vaccination and infection with age.