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.
Original language | English (US) |
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Pages (from-to) | 442-455 |
Number of pages | 14 |
Journal | Annals of neurology |
Volume | 87 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2020 |
Funding
This study was supported by National Institue of Neurological Disorders and Stroke F31 NS105451\u201002 (S.S.), NIH R01 AG054429 (J.A.K.), and National Institue of Biomedical Imaging and Bioengineering R01 EB\u2010013198 (S.D.M.). This study was supported by National Institue of Neurological Disorders and Stroke F31 NS105451-02 (S.S.), NIH R01 AG054429 (J.A.K.), and National Institue of Biomedical Imaging and Bioengineering R01 EB-013198 (S.D.M.). We thank Dr D. Procissi, S. Meisner, and the Center of Translational Imaging at Northwestern University for assistance in acquiring and analyzing the magnetic resonance imaging data. We also thank Drs J. Jara and P. Ozdinler of the Ken and Ruth Davee Department of Neurology at Northwestern University in consulting and assistance with the controlled-cortical impact TBI model.
ASJC Scopus subject areas
- Neurology
- Clinical Neurology