Human umbilical cord blood cells rescued traumatic brain injury-induced cardiac and neurological deficits.

Abstract

BackgroundTraumatic brain injury (TBI) evokes neurological deficits and induces cardiac dysfunction. Treatment with human umbilical cord blood cells (HUCBCs) represents a potential therapeutic strategy for TBI-induced neurological deficits. The present study aimed to determine whether HUCBCs could ameliorate the cardiac dysfunction and neurological deficits induced by TBI.MethodsAdult male C57BL/6J mice were subjected to controlled cortical impact (CCI)-induced TBI and were treated with either HUCBCs (1×106) or phosphate-buffered saline (PBS), via tail vein injections, 3 days after TBI. Neurological and cognitive functions were subsequently evaluated at multiple time points after TBI and cardiac function was assessed by echocardiography 3 and 30 days after TBI. Brain and heart tissues were paraffin-embedded 30 days after TBI. Hematoxylin and eosin (H&E) staining was performed on brain tissue sections to calculate the brain damage volume, and Picro Sirius Red (PSR) staining was performed on heart tissue sections to evaluate myocardial fibrosis. Terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) staining was employed to assess cell apoptosis 30 days after TBI. Transforming growth factor-beta (TGF-β) and NADPH oxidase-2 (NOX2) levels were assessed to evaluate inflammation and oxidative stress levels 30 days after TBI.ResultsTBI elicited acute and chronic cardiac deficits, identified by decreased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) values 3 and 30 days after TBI, in addition to neurological and cognitive deficits. TBI mice treated with HUCBCs exhibited enhanced LVEF and FS values 30 days after TBI compared with untreated TBI controls. HUCBC treatment significantly improved neurological and cognitive functions and reduced cardiomyocyte apoptosis, inflammatory response, oxidative stress, and cardiac fibrosis in heart tissues 30 days after TBI.ConclusionsTBI induced both neurological deficits and cardiac dysfunction in mice, which were ameliorated by HUCBC treatment. The anti-inflammatory activities of HUCBCs may contribute to these observed therapeutic effects.