Background The anti-inflammatory cytokine interleukin-10 (IL-10) has been explored previously as a treatment method for spinal cord injury (SCI) due to its ability to attenuate pro-inflammatory cytokines and reduce apoptosis. Primary limitations when using systemic injections of IL-10 are that it is rapidly cleared from the injury site and that it does not cross the blood–spinal cord barrier. Objective Here, mineral-coated microparticles (MCMs) were used to obtain a local sustained delivery of IL-10 directly into the injury site after SCI. Methods Female Sprague-Dawley rats were contused at T10 and treated with either an intraperitoneal injection of IL-10, an intramedullary injection of IL-10, or MCMs bound with IL-10 (MCMs+IL-10). After treatment, cytokine levels were measured in the spinal cord, functional testing and electrophysiology were performed, axon tracers were injected into the brainstem and motor cortex, macrophage levels were counted using flow cytometry and immunohistochemistry, and lesion size was measured. Results When treated with MCMs+IL-10, IL-10 was significantly elevated in the injury site and inflammatory cytokines were significantly suppressed, prompting significantly less cells expressing antigens characteristic of inflammatory macrophages and significantly more cells expressing antigens characteristic of earlier stage anti-inflammatory macrophages. Significantly more axons were preserved within the rubrospinal and reticulospinal tracts through the injury site when treated with MCMs+IL-10; however, there was no significant difference in corticospinal tract axons preserved, regardless of treatment group. The rats treated with MCMs+IL-10 were the only group with a significantly higher functional score compared to injured controls 28 days post-contusion. Conclusion These data demonstrate that MCMs can effectively deliver biologically active IL-10 for an extended period of time altering macrophage phenotype and aiding in functional recovery after SCI.
Objective: To determine the relationship, if any, between dural venous sinus arachnoid granulations (AGs) and pulsatile tinnitus. Study Design: Retrospective case-control study. Methods: Between October 1999 and March 2020, magnetic resonance imaging of patients with tinnitus (pulsatile [PT] and nonpulsatile [NPT]) were assessed for the presence of dural venous sinuses AG. During the same interval, patients with AGs found incidentally on all magnetic resonance imagings ordered without an indication of tinnitus were reviewed. Demographic variables recorded included patient age, sex, race, body mass index, and a history of idiopathic intracranial hypertension (IIH) or obstructive sleep apnea. Location of AGs, when present, were recorded. Results: A total of 651 (PT 250, NPT 401) were found to have AGs. AGs had a higher prevalence in PT patients (10.4% [n = 26]) versus NPT patients (0.3% [n = 1]; odds ratio, 31.0; confidence interval 4.1-234; p < 0.001). Of the 77,607 patients who had an indication for imaging other than tinnitus, 230 patients (0.30%) were found to have incidental AGs, suggesting that the NPT cohort was an adequate control. Patients with PTwere more likely to have a higher body mass index, be female, be non-White, and have an existing diagnosis of IIH. For all patients with AGs, AGs were more likely to be found in the lateral sinuses (i.e., sigmoid, transverse) in the PT group (odds ratio, 8.1; confidence interval, 1.1-61.1; p = 0.0218). Conclusions: This study evaluates the association between AG and PT, finding higher rates of AG in patients with PT than in NPT. However, despite the increased prevalence of AG in patients with IIH, these data combined with existing literature would suggest that AGs are not necessarily the missing link to explain PT pathophysiology in IIH.
Spinal cord injury often results in devastating consequences for those afflicted, with very few therapeutic options. A central element of spinal cord injuries is astrogliosis, which forms a glial scar that inhibits neuronal regeneration post‐injury. Chondroitinase ABC (ChABC) is an enzyme capable of degrading chondroitin sulfate proteoglycan (CSPG), the predominant extracellular matrix component of the glial scar. However, poor protein stability remains a challenge in its therapeutic use. Messenger RNA (mRNA) delivery is an emerging gene therapy technology for in vivo production of difficult‐to‐produce therapeutic proteins. Here, mineral‐coated microparticles as an efficient, non‐viral mRNA delivery vehicles to produce exogenous ChABC in situ within a spinal cord lesion are used. ChABC production reduces the deposition of CSPGs in an in vitro model of astrogliosis, and direct injection of these microparticles within a glial scar forces local overexpression of ChABC and improves recovery of motor function seven weeks post‐injury.
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