Age and facial nerve axotomy-induced T cell trafficking: Relation to microglial and motor neuron status

Following peripheral axotomy of the facial nerve in mice, T lymphocytes cross the blood–brain-barrier (BBB) into the central nervous system (CNS), where they home to the neuronal cell bodies of origin in the facial motor nucleus (FMN) and act in concert with microglial cells to support the injured motor neurons. Several lines of evidence suggested normal aging may alter the injury-related responses of T cells, microglia, and motor neurons in this model. In this study, we therefore sought to test the hypothesis that compared to 8-week-old mice (young adult), 52-week-old mice (advanced middle age) would exhibit more neuronal damage and increased T cell trafficking into the injured FMN following facial nerve resection. Comparison of 8- and 52-week-old mice at 7, 14, 21, and 28 days post-resection of the facial nerve, confirmed our hypothesis that age influences the kinetics of CD3+ T lymphocyte trafficking in the axotomized FMN. The peak T cell response was significantly higher, occurred later, and remained elevated longer in the injured FMN of mice in the 52 week age group. Although the kinetics of motor neuron death (identified by quantifying CD11b+ perineuronal microglial phagocytic clusters engulfing the dead neurons at 7, 14, 21, and 28 days post-resection) differed between the age groups, motor neuron profile counts at day 28 showed that levels of cumulative motor neuron loss did not differ between the age groups. Compared to 8-week-old mice, however, there was small reduction in the mean cell size of the surviving motor neurons in the 52 week age group. Since T lymphocyte function decreases with normal aging, it will be important to determine if increased T cell trafficking into the injured CNS is a compensatory response to the decreased function of older T cells, and if these and related neuroimmunological changes are more pronounced in mice in the late stages of the life cycle.

Research highlights
► More CD3+ T cell in the injured FMN in 52-week-old mice than 8-week-old mice.
► Differences in CD11b+ clusters between 8- and 52-week-old mice in the injured FMN.
► Cumulative neuronal loss did not differ between 8- and 52-week-old mice.
► There was a small reduction in the size of the surviving motor neurons in older mice.