Background Spinal cord injury (SCI) is a condition with few effective treatment options. The blood-spinal cord barrier consists of pericytes, astrocytes, and endothelial cells, which are collectively termed the neurovascular unit. These cells support spinal cord homeostasis by expressing tight junction proteins. Physical trauma to the spinal cord disrupts the barrier, which leads to neuroinflammation by facilitating immune cell migration to the damaged site in a process involving immune cell adhesion. Immunosuppressive strategies, including methylprednisolone (MPSS), have been investigated to treat SCI. However, despite some success, MPSS has the potential to increase a patient’s susceptibility to wound infection and impaired wound healing. Hence, immunomodulation may be a more attractive approach than immunosuppression. Approved for modulating neuroinflammation in certain disorders, including Guillain-Barre syndrome, intravenous administration of human immunoglobulin G (hIgG) has shown promise in the setting of experimental SCI, though the optimal dose and mechanism of action remain undetermined. Methods Female adult Wistar rats were subjected to moderate-severe clip compression injury (35 g) at the C7-T1 level and randomized to receive a single intravenous (IV) bolus of hIgG (0.02, 0.2, 0.4, 1, 2 g/kg), MPSS (0.03 g/kg), or control buffer at 15 min post-SCI. At 24 h and 6 weeks post-SCI, molecular, histological, and neurobehavioral effects of hIgG were analyzed. Results At 24 h post-injury, human immunoglobulin G co-localized with spinal cord pericytes, astrocytes, and vessels. hIgG (2 g/kg) protected the spinal cord neurovasculature after SCI by increasing tight junction protein expression and reducing inflammatory enzyme expression. Improvements in vascular integrity were associated with changes in spinal cord inflammation. Interestingly, hIgG (2 g/kg) increased serum expression of inflammatory cytokines and co-localized (without decreasing protein expression) with spinal cord vascular cell adhesion molecule-1, a protein used by immune cells to enter into inflamed tissue. Acute molecular benefits of hIgG (2 g/kg) led to greater tissue preservation, functional blood flow, and neurobehavioral recovery at 6 weeks post-SCI. Importantly, the effects of hIgG (2 g/kg) were superior to control buffer and hIgG (0.4 g/kg), and comparable with MPSS (0.03 g/kg). Conclusions hIgG (2 g/kg) is a promising therapeutic approach to mitigate secondary pathology in SCI through antagonizing immune cell infiltration at the level of the neurovascular unit.

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Objective: To determine the association between delay in transfer to a central stroke unit from peripheral institutions and outcomes. Methods: We conducted a retrospective cohort study of all patients with acute stroke, admitted to a comprehensive stroke center (CSC) from three emergency departments (EDs), between 2016 and 2018. The primary outcomes were length of stay, functional status at 3 months, discharge destination, and time to stroke investigations. Results: One thousand four hundred thirty-five patients were included, with a mean age of 72.9 years, and 92.4% ischemic stroke; 663 (46.2%) patients were female. Each additional day of delay was associated with 2.0 days of increase in length of stay (95% confidence interval [CI] 0.8–3.2, p = 0.001), 11.5 h of delay to vascular imaging (95% CI 9.6–13.4, p < 0.0001), 24.2 h of delay to Holter monitoring (95% CI 7.9–40.6, p = 0.004), and reduced odds of nondisabled functional status at 3 months (odds ratio 0.98, 95% CI 0.96–1.00, p = 0.01). Factors affecting delay included stroke onset within 6 h of ED arrival (605.9 min decrease in delay, 95% CI 407.9–803.9, p < 0.0001), delay to brain imaging (59.4 min increase in delay for each additional hour, 95% CI 48.0–71.4, p < 0.0001), admission from an alternative service (3918.7 min increase in delay, 95% CI 3621.2–4079.9, p < 0.0001), and transfer from a primary stroke center (PSC; 740.2 min increase in delay, 95% CI 456.2–1019.9, p < 0.0001). Conclusion: Delay to stroke unit admission in a system involving transfer from PSCs to a CSC was associated with longer hospital stay and poorer functional outcomes.