Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway.

Traumatic brain injury (TBI) is a predominant cause of death and permanent disability globally. In recent years, much emphasis has been laid on treatments for TBI. Increasing evidence suggests that human umbilical cord mesenchymal stem cells (HUCMSCs) can improve neurological repair after TBI. However, the clinical use of HUCMSCs transplantation in TBI has been limited by immunological rejection, ethical issues, and the risk of tumorigenicity. Many studies have shown that HUCMSCs-derived exosomes may be an alternative approach for HUCMSCs transplantation. We hypothesized that exosomes derived from HUCMSCs could inhibit apoptosis after TBI, reduce neuroinflammation, and promote neurogenesis. A rat model of TBI was established to investigate the efficiency of neurological recovery with exosome therapy. We found that exosomes derived from HUCMSCs significantly ameliorated sensorimotor function and spatial learning in rats after TBI. Moreover, HUCMSCs-derived exosomes significantly reduced proinflammatory cytokine expression by suppressing the NF-κB signaling pathway. Furthermore, we found that HUCMSC-derived exosomes inhibited neuronal apoptosis, reduced inflammation, and promoted neuron regeneration in the injured cortex of rats after TBI. These results indicate that HUCMSCs-derived exosomes may be a promising therapeutic strategy for TBI.

TBHQ improved neurological recovery after traumatic brain injury by inhibiting the overactivation of astrocytes.

Traumatic brain injury (TBI) is a major leading cause of death and long-term disability. Although astrocytes play a key role in neuroprotection after TBI in the early stage, the overactivation of astrocytes can lead to long-term functional deficits, and the underlying pathophysiological mechanisms remain unclear. In addition, it is unknown whether the nuclear factor erythroid 2-related factor2/haem oxygenase-1 (Nrf-2/HO-1) pathway could elicit a neuroprotective effect by decreasing astrocyte overactivation after TBI. We aimed to study the effects of tert-butylhydroquinone (TBHQ) in reducing astrocyte overactivation after TBI and explored the underlying mechanisms. We first established a controlled cortical impact (CCI) model in rats and performed Haematoxylin and eosin (H&E) staining to observe brain tissue damage. The cognitive function of rats was assessed by modified neurological severity scoring (mNSS) and Morris water maze (MWM) test. Astrocyte and microglia activation was detected by immunofluorescence staining. Oxidative stress conditions were investigated using Western blotting. An enzyme-linked immunosorbent assay (ELISA) was designed to assess the level of the proinflammatory factor tumour necrosis factor-alpha (TNF-α). Dihydroethidium (DHE) staining was used to detect reactive oxygen species (ROS). Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The results showed that the administration of TBHQ ameliorated motor function and cognitive deficits and decreased the lesion volume. In addition, TBHQ significantly decreased astrocyte overactivation, diminished the pro-inflammatory phenotype M1 and inflammatory cytokines production after TBI, increased Nrf-2 nuclear accumulation, and enhanced the levels of the Nrf-2 downstream antioxidative genes HO-1 and NADPH-quinone oxidoreductase-1 (NQO-1). Furthermore, TBHQ treatment alleviated apoptosis and neuronal death in the cerebral cortex. Overall, our data indicated that the upregulation of Nrf-2 expression could enhance neuroprotection and decrease astrocyte overactivation and might represent a new theoretical basis for treating TBI.