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.

A Systematic Review and Meta-Analysis of the Inflammatory Biomarkers in Mild Traumatic Brain Injury

“…There were no significant concerns about publication bias and the quality of the studies (Figure 2A,B). The studies that were selected [15][16][17][18][19][20][21][22][23] evaluated between 9 and 104 mTBI patients in comparison to orthopedic injury patients or healthy controls. The blood samples were analyzed for protein expression or level changes in apolipoprotein, neuron-specific enolase (NSE), GFAP, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-17A, S100B, tau, TNF-α, CCL2, IFN-γ, fractalkine, NfL, and NSE.…”

“…• increased levels of IL-1β and IL-6 after mTBI; • overexpression of IL-8 and low expression of IL-4 in females that had undergone mTBI. [21] 83 individuals:…”

“…In severe TBI, IFN-ã was decreased compared to the controls. Zhao et al [21] showed that while both male and female patients had changes in the cerebral brain flow and increased levels of IL-1β and IL-6, female patients demonstrated overexpression of IL-8 and low expression of IL-4. Devoto et al [22] reported that IL-6 and TNF-α concentrations were higher in the TBI group than in the control group.…”

Arterial Spin Labeling (ASL) in Neuroradiological Diagnostics – Methodological Overview and Use Cases

“…Worldwide, it is estimated that over 60 million incidences of traumatic brain injury (TBI) occur every year, of which approximately 80 % are considered mild TBI (mTBI) based on initial symptom presentation [124][125][126]. Over the last decade, ASL has emerged as a promising imaging technique for the study of cerebral perfusion changes following moderate-to-severe TBI as well as mTBI [127][128][129][130][131][132][133][134][135][136][137][138][139][140].…”

Inflammatory Biomarkers in mTBI

“…Zhao et al [21] investigated the sex differences in CBF and serum inflammatory cytokines levels in patients with acute stage mTBI. The results showed that while both male and female patients had increased levels of IL-1β and IL-6, female patients demonstrated overexpression of IL-8 and low expression of IL-4.…”