Lentiviral Injection of Inter-α-Trypsin Inhibitor Heavy Chain 4 Promotes Female Spinal Cord Injury Mice Recuperation by Diminishing Peripheral and Central Inflammation.

Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) acts as a mediator of inflammation and extracellular matrix stabilization. The current study intended to delve into the impact of ITIH4 on locomotor performance, nerve injury, neuroinflammation, systemic inflammation, and the downstream pathway in spinal cord injury (SCI) mice. Overexpression lentivirus of ITIH4 (LV-ITIH4) and negative control lentivirus (LV-NC) were intravenously injected into adult C57BL/6 mice on 7 days before SCI surgery. All mice were euthanized on day 28 after SCI surgery, and their blood samples and spinal cord tissues were collected. Decreased relative gene expression and protein levels of ITIH4 were observed in SCI mice. LV-ITIH4 improved the locomotor performance compared to LV-NC in SCI mice. In spinal cord of SCI mice, LV-ITIH4 reduced apoptosis and increased survival of neurons compared to LV-NC. By comparison with LV-NC, LV-ITIH4 also reduced relative gene expressions of interleukin (IL)-6 and tumor necrosis factor-α in spinal cord of SCI mice. Moreover, LV-ITIH4 reduced microglia M1 polarization compared with LV-NC in spinal cord of SCI mice. In the serum, LV-ITIH4 decreased the protein levels of IL-6 and IL-1β compared to LV-NC in SCI mice. LV-ITIH4 also inhibited the nuclear factor kappa-B (NF-κB) pathway compared to LV-NC in spinal cord of SCI mice. ITIH4 enhances locomotor performance in SCI mice, and it inhibits nerve injury, neuroinflammation, systemic inflammation, and the NF-κB pathway in SCI mice.