Sex Differences in Cerebral Blood Flow and Serum Inflammatory Cytokines and Their Relationships in Mild Traumatic Brain Injury

Abstract

This study aimed to investigate sex differences in cerebral blood flow (CBF) and serum inflammatory cytokines, as well as their correlations in patients with acute-stage mild traumatic brain injury (mTBI). Forty-one patients with mTBI and 23 matched healthy controls underwent 3D-pseudo-continuous arterial spin labeling imaging on 3T magnetic resonance imaging. The patients underwent cognitive evaluations and measurement of a panel of ten serum cytokines: interleukin (IL)-1I, IL-4, IL-6, IL-8, IL-10, IL-12, C-C motif chemokine ligand 2, interferon-gamma, nerve growth factor-beta (β-NGF), and tumor necrosis factor-alpha (TNF-α). Spearman rank correlation analysis was performed to evaluate the relationship between inflammation levels and CBF. We found that both male and female patients showed increased IL-1L and IL-6 levels. Female patients also demonstrated overexpression of IL-8 and low expression of IL-4. As for CBF levels, three brain regions [the right superior frontal gyrus (SFG_R), left putamen, and right precuneus] increased in male patients while three brain regions [the right superior temporal gyrus (STG_R), left middle occipital gyrus, and right postcentral (PoCG_R)] decreased in female patients. Furthermore, the STG_R in female controls was positively correlated with β-NGF while the right PoCG_R in female patients was negatively correlated with IL-8. In addition, compared with male patients, female patients showed decreased CBF in the right pallidum, which was negatively correlated with IL-8. These findings revealed abnormal expression of serum inflammatory cytokines and CBF levels post-mTBI. Females may be more sensitive to inflammatory and CBF changes and thus more likely to get cognitive impairment. This may suggest the need to pay closer attention to the female mTBI group.

Keywords: cerebral blood flow; cognitive impairment; correlation analysis; mild traumatic brain injury; serum inflammatory cytokines.

Figure 1

Results of brain region changes in mTBI female patients compared with female controls. The CBF of female patients in right superior temporal gyrus (A), left middle occipital gyrus (B), and right postcentral gyrus (C) showed decreased perfusion levels compared with female controls. mTBI, mild traumatic brain injury; CBF, cerebral blood flow.

Figure 2

Results of brain region changes in mTBI male patients compared with male controls. The CBF of male patients in right superior frontal gyrus (A), left putamen (B), and right precuneus (C) showed increased perfusion levels compared with male controls. mTBI, mild traumatic brain injury; CBF, cerebral blood flow.

Figure 3

Results of brain region changes in mTBI male patients compared with female patients. The CBF of male patients in left precuneus (A) is lower than female patients, while the right pallidum (B) showed increased perfusion levels. mTBI, mild traumatic brain injury; CBF, cerebral blood flow.

Figure 4

Results of correction between CBF and serum inflammatory factors. (A) Decreased CBF perfusion in the right superior temporal gyrus in female controls was associated with decreased β-NGF, which was positively correlated. (B) In female patients, CBF level in the right posterior central gyrus was negatively correlated with inflammatory factor IL-8. (C) In the right pallidum, the higher the IL-8 concentration is, the lower the blood volume level in that area. CBF, cerebral blood flow; β-NGF, nerve growth factor beta; IL-8, interleukin 8.