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Intravenous Immunomodulatory Nanoparticle Treatment for Traumatic Brain Injury.

ABSTRACT: OBJECTIVE:There are currently no definitive disease-modifying therapies for traumatic brain injury (TBI). In this study, we present a strong therapeutic candidate for TBI, immunomodulatory nanoparticles (IMPs), which ablate a specific subset of hematogenous monocytes (hMos). We hypothesized that prevention of infiltration of these cells into brain acutely after TBI would attenuate secondary damage and preserve anatomic and neurologic function. METHODS:IMPs, composed of US Food and Drug Administration-approved 500nm carboxylated-poly(lactic-co-glycolic) acid, were infused intravenously into wild-type C57BL/6 mice following 2 different models of experimental TBI, controlled cortical impact (CCI), and closed head injury (CHI). RESULTS:IMP administration resulted in remarkable preservation of both tissue and neurological function in both CCI and CHI TBI models in mice. After acute treatment, there was a reduction in the number of immune cells infiltrating into the brain, mitigation of the inflammatory status of the infiltrating cells, improved electrophysiologic visual function, improved long-term motor behavior, reduced edema formation as assessed by magnetic resonance imaging, and reduced lesion volumes on anatomic examination. INTERPRETATION:Our findings suggest that IMPs are a clinically translatable acute intervention for TBI with a well-defined mechanism of action and beneficial anatomic and physiologic preservation and recovery. Ann Neurol 2020;87:442-455.

SUBMITTER: Sharma S

PROVIDER: S-EPMC7296512 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Intravenous Immunomodulatory Nanoparticle Treatment for Traumatic Brain Injury.

Sharma Sripadh S Ifergan Igal I Kurz Jonathan E JE Linsenmeier Robert A RA Xu Dan D Cooper John G JG Miller Stephen D SD Kessler John A JA

Annals of neurology 20200122 3

<h4>Objective</h4>There are currently no definitive disease-modifying therapies for traumatic brain injury (TBI). In this study, we present a strong therapeutic candidate for TBI, immunomodulatory nanoparticles (IMPs), which ablate a specific subset of hematogenous monocytes (hMos). We hypothesized that prevention of infiltration of these cells into brain acutely after TBI would attenuate secondary damage and preserve anatomic and neurologic function.<h4>Methods</h4>IMPs, composed of US Food and ...[more]

PMID: 31925846

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Project description:ImportanceThere are limited data on which factors affect the critical and complex decision to withdraw life-supporting treatment (LST) in patients with severe traumatic brain injury (sTBI).ObjectiveTo determine demographic and clinical factors associated with the decision to withdraw LST in patients with sTBI.Design, setting, and participantsThis retrospective analysis of inpatient data from more than 825 trauma centers across the US in the American College of Surgeons Trauma Quality Improvement Program database from January 2013 to December 2015 included adult patients with sTBI and documentation of a decision regarding withdrawal of LST (WLST). Data analysis was conducted in September 2019.Main outcomes and measuresFactors associated with WLST in sTBI.ResultsA total of 37931 patients (9817 women [25.9%]) were included in the multivariable analysis; 7864 (20.7%) had WLST. Black patients (4806 [13.2%]; odds ratio [OR], 0.66; 95% CI, 0.59-0.72; P < .001) and patients of other race (4798 [13.2%]; OR, 0.83; 95% CI, 0.76-0.91; P < .001) were less likely than white patients (26 864 [73.7%]) to have WLST. Patients from hospitals in the Midwest (OR, 1.12; 95% CI, 1.04-1.20; P = .002) or Northeast (OR, 1.23; 95% CI, 1.13-1.34; P < .001) were more likely to have WLST than patients from hospitals in the South. Patients with Medicare (OR, 1.55; 95% CI, 1.43-1.69; P < .001) and self-pay patients (OR, 1.36; 95% CI, 1.25-1.47; P < .001) were more likely to have WLST than patients with private insurance. Older patients and those with lower Glasgow Coma Scale scores, higher Injury Severity Scores, or craniotomy were generally more likely to have WLST. Withdrawal of LST was more likely for patients with functionally dependent health status (OR, 1.30; 95% CI, 1.08-1.58; P = .01), hematoma (OR, 1.19; 95% CI, 1.12-1.27; P < .001), dementia (OR, 1.29; 95% CI, 1.08-1.53; P = .004), and disseminated cancer (OR, 2.82; 95% CI, 2.07-3.82; P < .001) than for patients without these conditions.Conclusions and relevanceWithdrawal of LST is common in sTBI and socioeconomic factors are associated with the decision to withdraw LST. These results highlight the many factors that contribute to decision-making in sTBI and demonstrate that in a complex and variable disease process, variation based on race, payment, and region presents as a potential challenge.

Dataset Information

Intravenous Immunomodulatory Nanoparticle Treatment for Traumatic Brain Injury.

Publications

Intravenous Immunomodulatory Nanoparticle Treatment for Traumatic Brain Injury.

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