Multiparity Differentially Affects Specific Aspects of the Acute Neuroinflammatory Response to Traumatic Brain Injury in Female Mice.

Pregnancy is associated with profound acute and long-term physiological changes, but the effects of such changes on brain injury outcomes are unclear. Here, we examined the effects of previous pregnancy and maternal experience (parity) on acute neuroinflammatory responses to lateral fluid percussion injury (FPI), a well-defined experimental traumatic brain injury (TBI) paradigm. Multiparous (2-3 pregnancies and motherhood experiences) and age-matched nulliparous (no previous pregnancy or motherhood experience) female mice received either FPI or sham injury and were euthanized 3 days post-injury (DPI). Increased cortical Iba1, GFAP, and CD68 immunolabeling was observed following TBI independent of parity and microglia morphology did not differ between TBI groups. However, multiparous females had fewer CD45 cells near the site of injury compared to nulliparous females, which was associated with preserved aquaporin-4 polarization, suggesting that parity may influence leukocyte recruitment to the site of injury and maintenance of blood brain barrier permeability following TBI. Additionally, relative cortical Il6 gene expression following TBI was dependent on parity such that TBI increased Il6 expression in nulliparous, but not multiparous, mice. Together, this work suggests that reproductive history may influence acute neuroinflammatory outcomes following TBI in females.