The effects of self-assembling peptide on glial cell activation.

Glial cells play a critical role in the healthy and diseased phases of the central nervous system (CNS). CNS diseases involve a wide range of pathological conditions characterized by poor recovery of neuronal function. Glial cell-related target therapies are progressively gaining interest in inhibiting secondary injury-related death. Modulation of the extracellular matrix by artificial scaffolds plays a critical role in the behavior of glial cells after injury. Among numerous types of scaffolds, self-assembling peptides (SAPs) notably give attention to the design of a proper biophysical and biomechanical microenvironment for cellular homeostasis and tissue regeneration. Implementing SAPs in an injured brain can induce neural differentiation in transplanted stem cells, reducing inflammation and inhibiting glial scar formation. In this review, we investigate the recent findings to elucidate the pivotal role of SAPs in orchestrating the most pivotal secondary response following CNS injury. Notably, we explore their impact on the activation of glial cells and their modulatory effects on microglial and astrocytic polarization.

Correlation of ammonia and blood laboratory parameters with hepatic encephalopathy: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Emerging research suggests that hyperammonemia may enhance the probability of hepatic encephalopathy (HE), a condition associated with elevated levels of circulating ammonia in patients with cirrhosis. However, some studies indicate that blood ammonia levels may not consistently correlate with the severity of HE, highlighting the complex pathophysiology of this condition. METHODS: A systematic review and meta-analysis through PubMed, Scopus, Embase, Web of Science, and Virtual Health Library were conducted to address this complexity, analyzing and comparing published data on various laboratory parameters, including circulating ammonia, blood creatinine, albumin, sodium, and inflammation markers in cirrhotic patients, both with and without HE. RESULTS: This comprehensive review, which included 81 studies from five reputable databases until June 2024, revealed a significant increase in circulating ammonia levels in cirrhotic patients with HE, particularly those with overt HE. Notably, significant alterations were observed in the circulating creatinine, albumin, sodium, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) in HE patients. CONCLUSIONS: These findings suggest an association between ammonia and HE and underscore the importance of considering other blood parameters such as creatinine, albumin, sodium, and pro-inflammatory cytokines when devising new treatment strategies for HE.

The interaction between cannabinoids and long-term synaptic plasticity: A survey on memory formation and underlying mechanisms.

Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is an essential phenomenon in memory formation as well as maintenance along with many other cognitive functions, such as those needed for coping with external stimuli. Synaptic plasticity consists of gradual changes in the biochemistry and morphology of pre- and postsynaptic neurons, particularly in the hippocampus. Consuming marijuana as a primary source of exocannabinoids immediately impairs attention and working memory-related tasks. Evidence regarding the effects of cannabinoids on LTP and memory is contradictory. While cannabinoids can affect a variety of specific cannabinoid receptors (CBRs) and nonspecific receptors throughout the body and brain, they exert miscellaneous systemic and local cerebral effects. Given the increasing use of cannabis, mainly among the young population, plus its potential adverse long-term effects on learning and memory processes, it could be a future global health challenge. Indeed, the impact of cannabinoids on memory is multifactorial and depends on the dosage, timing, formula, and route of consumption, plus the background complex interaction of the endocannabinoids system with other cerebral networks. Herein, we review how exogenously administrated organic cannabinoids, CBRs agonists or antagonists, and endocannabinoids can affect LTP and synaptic plasticity through various receptors in interaction with other cerebral pathways and primary neurotransmitters.

MicroRNA (miRNA) as a biomarker for diagnosis, prognosis, and therapeutics molecules in neurodegenerative disease.

Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) that arise due to numerous causes like protein accumulation and autoimmunity characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform an important role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. miRNA that participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative disease (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlight miRNA as therapy.

Evaluation of the Safety and Efficacy of Repeated Mesenchymal Stem Cell Transplantations in ALS Patients by Investigating Patients' Specific Immunological and Biochemical Biomarkers.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell (MSC) therapy cohort as a promising novel treatment modality by estimating some additional new parameters, such as immunological and biochemical factors. METHODS: This study was designed as an open-label, one-arm cohort retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous-bone marrow-derived mesenchymal stem cells (BM-MSCs) in 15 confirmed patients with ALS, administered at a dose of 1 × 106 cells/kg BW with a one-month interval, in equal amounts in both an intravenous (IV) and intrathecal (IT) capacity simultaneously, via various biochemical (iron (Fe), ferritin, total-iron-binding capacity (TIBC), transferrin, and creatine kinase (CK)) and immunological parameters (tumor necrosis factor-alpha (TNF-α), neurofilament light chain (NFL), and glial-cell-derived neurotrophic factor (GDNF) levels, evaluated during the three-month follow-up period in serum and cerebrospinal fluid (CSF). RESULTS: Our study indicated that, in the case of immunological biomarkers, TNF-α levels in the CSF showed a significant decrease at month three after transplantation compared with levels at month zero, and the p-value was p < 0.01. No statistically significant changes were observed for other immunological as well as biochemical parameters and a p-value of p > 0.05. CONCLUSIONS: These results can indicate the potential benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results.

Human Endometrial Regenerative Cells for Neurological Disorders: Hype or Hope?

Despite enormous efforts, no effective medication has been found to significantly halt or even slow the progression of neurological diseases, such as acquired (e.g., traumatic brain injury, spinal cord injury, etc.) and chronic (e.g., Parkinson's disease, Alzheimer's disease, etc.) central nervous system disorders. So, researchers are looking for alternative therapeutic modalities to manage the disease's symptoms and stop it from worsening. Concerning disease-modifying capabilities, stem cell therapy has emerged as an expanding domain. Among different types of stem cells, human endometrial regenerative cells have excellent regenerative properties, making them suitable for regenerative medicine. They have the potential for self-renewal and differentiation into three types of stem cells: epithelial stem cells, endothelial side population stem cells, and mesenchymal stem cells (MSCs). ERCs can be isolated from endometrial biopsy and menstrual blood samples. However, there is no comprehensive evidence on the effects of ERCs on neurological disorders. Hence, we initially explore the traits of these specific stem cells in this analysis, followed by an emphasis on their therapeutic potential in treating neurological disorders.

Effect of a combined program of running exercise and environmental enrichment on memory function and neurogenesis markers in amyloid-beta-induced Alzheimer-like model.

Objectives: It is urgent to develop non-pharmacological interventions or multifactor combination approaches to combat Alzheimer's disease (AD). The effect of exercise (EX) combined with environmental enrichment (EE) on behavioral phenotypes and neurogenesis markers in an Alzheimer-like rat model was investigated. Materials and Methods: The groups consisted of AD, sham-operated, AD+EX, AD+EE, and AD+EX+EE. AD was produced by injection of amyloid-beta (1-42, 6 µg) intrahippocampally, and a daily treadmill for 3 consecutive weeks was used for EX animals. EE was a large cage (50× 50× 50 cm) containing differently shaped objects. Spatial learning and memory were evaluated in the Morris water maze (MWM), and a shuttle box was used to evaluate inhibitory avoidance memory. RT-PCR was performed to assess the expression of early neurogenesis markers, DCX, and Sox2 within the hippocampus. Results: Pretreatment with exercise and EE, both individually and in combination, could provide protection from memory impairments in AD rats. Combined treatment led to a significantly more pronounced improvement in memory deficits of AD rats than either paradigm alone. Combination therapy with exercise and EE could also reverse the passive avoidance memory impairment and hippocampal DCX expression of AD rats to the control levels. Conclusion: These data suggest that exercise in combination with cognitive engagement can provide a non-pharmacological and multidomain policy that may prevent or delay AD symptoms.

Oxidative stress is a new avenue for treatment of neuropsychiatric disorders: hype of hope?

The biochemical integrity of the brain is critical in maintaining normal central nervous system (CNS) functions. One of the factors that plays an important role in causing biochemical impairment of the brain is known as oxidative stress. Oxidative stress is generally defined as the excessive formation of free radicals relative to antioxidant defenses. The brain is particularly susceptible to oxidative stress because of its high oxygen consumption and lipid-rich content. Therefore, oxidative stress damage is associated with abnormal CNS function. Psychiatric disorders are debilitating diseases. The underlying pathophysiology of psychiatric disorders is poorly defined and may involve the interplay of numerous clinical factors and mechanistic mechanisms. Considerable evidence suggests that oxidative stress plays a complex role in several neuropsychiatric disorders, including anxiety, bipolar disorder, depression, obsessivecompulsive disorder, panic disorder, and schizophrenia. To address these issues, we reviewed the literature and considered the role of oxidative stress as one of the first pathological changes in the course of neuropsychiatric disorders, which should receive more attention in future research.

Inhibition of autotaxin alleviates pathological features of hepatic encephalopathy at the level of gut-liver-brain axis: an experimental and bioinformatic study.

There is accumulating evidence that the circulatory levels of autotaxin (ATX) and lysophosphatidic acid (LPA) are increased in patients with severe liver disease. However, the potential role of the ATX-LPA axis in hepatic encephalopathy (HE) remains unclear. Our study aimed to investigate the role of the ATX-LPA signaling pathway in mice with thioacetamide (TAA) induced acute HE. To show the role of the ATX-LPA axis in the context of HE, we first measured the involvement of ATX-LPA in the pathogenesis of TAA-induced acute HE. Then, we compared the potential effects of ATX inhibitor (HA130) on astrocyte responses at in vitro and gut-liver-brain axis at in vivo levels. The inflammatory chemokine (C-C motif) ligand 3 was significantly increased in the hyperammonemic condition and could be prevented by ATX inhibition in astrocytes at in vitro level. Further statistical tests revealed that plasma and tissue pro-inflammatory cytokines were inhibited by HA130 in mice. Furthermore, the stage of HE was significantly improved by HA130. The most surprising result was that HA130 alleviated immune infiltrating cells in the liver and intestine and decreased mucus-secreting cells in the intestine. Further analysis showed that the levels of liver enzymes in serum were significantly decreased in response to ATX inhibition. Surprisingly, our data indicated that HA130 could recover permeabilization of the blood-brain barrier, neuroinflammation, and recognition memory. Besides that, we found that the changes of Interleukin-1 (IL-1) and aquaporin-4 (AQP4) in HE might have a connection with the glymphatic system based on bioinformatics analyses. Taken together, our data showed that the ATX-LPA axis contributes to the pathogenesis of HE and that inhibition of ATX improves HE.

Mesenchymal stem cell therapy in amyotrophic lateral sclerosis (ALS) patients: A comprehensive review of disease information and future perspectives.

Amyotrophic lateral sclerosis (ALS) is a rare deadly progressive neurological disease that primarily affects the upper and lower motor neurons with an annual incidence rate of 0.6 to 3.8 per 100,000 people. Weakening and gradual atrophy of the voluntary muscles are the first signs of the disease onset affecting all aspects of patients' lives, including eating, speaking, moving, and even breathing. Only 5-10% of patients have a familial type of the disease and show an autosomal dominant pattern, but the cause of the disease is unknown in the remaining 90% of patients (Sporadic ALS). However, in both types of disease, the patient's survival is 2 to 5 years from the disease onset. Some clinical and molecular biomarkers, magnetic resonance imaging (MRI), blood or urine test, muscle biopsy, and genetic testing are complementary methods for disease diagnosis. Unfortunately, with the exception of Riluzole, the only medically approved drug for the management of this disease, there is still no definitive cure for it. In this regard, the use of mesenchymal stem cells (MSCs) for the treatment or management of the disease has been common in preclinical and clinical studies for many years. MSCs are multipotent cells having immunoregulatory, anti-inflammatory, and differentiation ability that makes them a good candidate for this purpose. This review article aims to discuss multiple aspects of ALS disease and focus on MSCs' role in disease management based on performed clinical trials.

Gut Dysbiosis and Blood-Brain Barrier Alteration in Hepatic Encephalopathy: From Gut to Brain.

A common neuropsychiatric complication of advanced liver disease, hepatic encephalopathy (HE), impacts the quality of life and length of hospital stays. There is new evidence that gut microbiota plays a significant role in brain development and cerebral homeostasis. Microbiota metabolites are providing a new avenue of therapeutic options for several neurological-related disorders. For instance, the gut microbiota composition and blood-brain barrier (BBB) integrity are altered in HE in a variety of clinical and experimental studies. Furthermore, probiotics, prebiotics, antibiotics, and fecal microbiota transplantation have been shown to positively affect BBB integrity in disease models that are potentially extendable to HE by targeting gut microbiota. However, the mechanisms that underlie microbiota dysbiosis and its effects on the BBB are still unclear in HE. To this end, the aim of this review was to summarize the clinical and experimental evidence of gut dysbiosis and BBB disruption in HE and a possible mechanism.

The Glymphatic System May Play a Vital Role in the Pathogenesis of Hepatic Encephalopathy: A Narrative Review.

Hepatic encephalopathy (HE) is a neurological complication of liver disease resulting in cognitive, psychiatric, and motor symptoms. Although hyperammonemia is a key factor in the pathogenesis of HE, several other factors have recently been discovered. Among these, the impairment of a highly organized perivascular network known as the glymphatic pathway seems to be involved in the progression of some neurological complications due to the accumulation of misfolded proteins and waste substances in the brain interstitial fluids (ISF). The glymphatic system plays an important role in the clearance of brain metabolic derivatives and prevents aggregation of neurotoxic agents in the brain ISF. Impairment of it will result in aggravated accumulation of neurotoxic agents in the brain ISF. This could also be the case in patients with liver failure complicated by HE. Indeed, accumulation of some metabolic by-products and agents such as ammonia, glutamine, glutamate, and aromatic amino acids has been reported in the human brain ISF using microdialysis technique is attributed to worsening of HE and correlates with brain edema. Furthermore, it has been reported that the glymphatic system is impaired in the olfactory bulb, prefrontal cortex, and hippocampus in an experimental model of HE. In this review, we discuss different factors that may affect the function of the glymphatic pathways and how these changes may be involved in HE.

Leukemia-derived Exosomes Can Induce Responses Related to Tumorigenesis on Non-tumoral Astrocytes.

Cancer is the second cause of disability and death worldwide. Identifying communication between cancer cells and normal cells can shed light on the underlying metastatic mechanisms. Among different suspected mechanisms, exosomes derived from cancer cells have been introduced as a main key player in metastatic processes. To this point, we evaluated the effects of exosomes derived from the leukemia nalm6 cell line on astrocytes behavior, such as proliferation and inflammatory pathways. To assess astrocyte responses, data were obtained by MTT, Annexin/PI to indicate proliferation and apoptosis. Further analyses were performed by Real-time PCR and western blot to assess the expression of IL6, IL1ß, NFkß, TNFα, and aquaporin-4 (AQP4). Our results demonstrated that the proliferation of astrocytes was significantly increased when treated with exosomes derived from Nalm6 cells. We also found that the expression of IL6, IL1ß, NFkß, and TNFα were significantly increased at the mRNA level when exposed to exosomes derived from Nalm6 cells. Finally, the mRNA and protein levels of AQP4 were profoundly increased after being treated by exosomes derived from Nalm6 cells. To sum up, our data indicated that the secretion of cancer cells could induce responses related to tumorigenesis. However, further studies on this topic are warranted to clarify exosomes' role in metastasis.

Reactogenicity within the first week after Sinopharm, Sputnik V, AZD1222, and COVIran Barekat vaccines: findings from the Iranian active vaccine surveillance system.

BACKGROUND: This study aimed to evaluate the reactogenicity effects of COVID-19 vaccines, used in Iran. METHODS: At least 1000 people were followed up with phone calls or self-report in a mobile application within 7 days after vaccination. Local and systemic reactogenicities were reported overall and by subgroups. RESULTS: The presence of one or more local and systemic adverse effects after the first dose of vaccines was 58.9% [(95% Confidence Intervals): 57.5-60.3)] and 60.5% (59.1-61.9), respectively. These rates were reduced to 53.8% (51.2-55.0) and 50.8% (48.8-52.7) for the second dose. The most common local adverse effect reported for all vaccines was pain in the injection site. During the first week after the first dose of vaccines, the frequency of the pain for Sinopharm, AZD1222, Sputnik V, and Barekat was 35.5%, 86.0%, 77.6%, and 30.9%, respectively. The same rates after the second dose were 27.3%, 66.5%, 63.9%, and 49.0%. The most common systemic adverse effect was fatigue. In the first dose, it was 30.3% for Sinopharm, 67.4% for AZD1222, 47.6% for Sputnik V, and 17.1% for Barekat. These rates were reduced to 24.6%, 37.1%, 36.5%, and 19.5%, in the second dose of vaccines. AZD1222 had the highest local and systemic adverse effects rates. The odds ratio of local adverse effects of the AZD1222 vaccine compared to the Sinopharm vaccine were 8.73 (95% CI 6.93-10.99) in the first dose and 4.14 (95% CI 3.32-5.17) in the second dose. Barekat and Sinopharm had the lowest frequency of local and systemic adverse effects. Compared to Sinopharm, systemic adverse effects were lower after the first dose of Barekat (OR = 0.56; 95% CI 0.46-0.67). Reactogenicity events were higher in women and younger people. Prior COVID-19 infection increased the odds of adverse effects only after the first dose of vaccines. CONCLUSIONS: Pain and fatigue were the most common reactogenicities of COVID-19 vaccination. Reactogenicities were less common after the second dose of the vaccines. The adverse effects of AZD1222 were greater than those of other vaccines.

Mephedrone induced apoptosis and impaired neurogenesis in embryonic neural stem/progenitor cells.

Mephedrone, a synthetic derivative of cathinone, is a commonly used psychoactive substance. Our previous study showed that exposure to mephedrone during pegnancy induced antiproliferative and pro-apoptotic effects in hippocampus of mice delivered pups. However, its effects on neural stem/progenitor cells (NS/PC) remain unexplored. The aim of this study is to investigate the effects of mephedrone exposure on the proliferation, differentiation, and apoptosis of rat embryonic NS/PC. NS/PC were isolated from rat fetal ganglionic eminence region at embryonic day 14.5. The effects of mephedrone on cell proliferation, neurosphere formation (colonies of NS/PC), neuronal differentiation, and apoptosis of NS/PC were assessed using MTT, immunocytochemistry, and flow cytometry. Mephedrone at concentrations of 20-640 µM significantly decreased the proliferation of NS/PC, induced cell cycle arrest, and enhanced the percent of apoptotic and necrotic cells. Neurosphere assays revealed a significant reduction in the number and diameter of neurosphere-forming cells. In addition, mephedrone significantly decreased the expressions of DCX and NeuN neuronal markers. Taken together, our results suggeste that exposure to mephedrone decreases the viability and neuronal differentiation of embryonic NS/PC. This study showed that mephedrone exposure during fetal or neonatal life may impair neurogenesis and subsequent brain development.

New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets.

Hepatic encephalopathy (HE) is a set of complex neurological complications that arise from advanced liver disease. The precise molecular and cellular mechanism of HE is not fully understood. Differentially expressed genes (DEGs) from microarray technologies are powerful approaches to obtain new insight into the pathophysiology of HE. We analyzed microarray data sets of cirrhotic patients with HE from Gene Expression Omnibus to identify DEGs in postmortem cerebral tissues. Consequently, we uploaded significant DEGs into the STRING to specify protein-protein interactions. Cytoscape was used to reconstruct the genetic network and identify hub genes. Target genes were uploaded to different databases to perform comprehensive enrichment analysis and repurpose new therapeutic options for HE. A total of 457 DEGs were identified in 2 data sets totally from 12 cirrhotic patients with HE compared with 12 healthy subjects. We found that 274 genes were upregulated and 183 genes were downregulated. Network analyses on significant DEGs indicated 12 hub genes associated with HE. Enrichment analysis identified fatty acid beta-oxidation, cerebral organic acidurias, and regulation of actin cytoskeleton as main involved pathways associated with upregulated genes; serotonin receptor 2 and ELK-SRF/GATA4 signaling, GPCRs, class A rhodopsin-like, and p38 MAPK signaling pathway were related to downregulated genes. Finally, we predicted 39 probable effective drugs/agents for HE. This study not only confirms main important involved mechanisms of HE but also reveals some yet unknown activated molecular and cellular pathways in human HE. In addition, new targets were identified that could be of value in the future study of HE.

Exosomes and Nano-SDF Scaffold as a Cell-Free-Based Treatment Strategy Improve Traumatic Brain Injury Mechanisms by Decreasing Oxidative Stress, Neuroinflammation, and Increasing Neurogenesis.

Traumatic brain injury (TBI) causes a variety of complex pathological changes in brain parenchymal tissue by increasing neuroinflammatory and apoptosis responses. Currently, there is no treatment to resolve the consequences related to TBI. Recently, an extensive literature has grown up around the theme of bystander effects of stem cells, a mechanism of stem cells without the need for cell transplantation, which is called cell-free therapy. The purpose of this investigation was to determine the efficacy of a cell-free-based therapy strategy using exosomes derived from human neural stem cells (hNSCs) and a novel nano-scaffold in rats subjected to TBI. In this study, a series of in vitro and in vivo experiments from behavior tests to gene expression was performed to define the effect of exosomes in combination with a three-dimensional (3D) nano-scaffold containing a bio-motif of SDF1α (Nano-SDF). Application of exosomes with Nano-SDF significantly decreased oxidative stress in serum and brain samples. Moreover, treatment with exosomes and Nano-SDF significantly reduced the expression of Toll-like receptor 4 and its downstream signaling pathway, including NF-kß and interleukin-1ß. We also found that the cell-free-based therapy strategy could decrease reactive gliosis at the injury site. Interestingly, we showed that exosomes with Nano-SDF increased neurogenesis in the sub-ventricular zone of the lateral ventricle, indicating a bio-bridge mechanism. To sum up, the most obvious finding to emerge from this study is that a cell-free-based therapy strategy can be an effective option for future practice in the course of TBI.

Monkeypox virus from neurological complications to neuroinvasive properties: current status and future perspectives.

Cases of monkeypox (MPV) are sharply rising around the world. While most efforts are being focused on the management of the first symptoms of monkeypox, such as cutaneous lesions and flu-like symptoms, the effect of the monkeypox virus (MPXV) on multiple organs still remains unclear. Recently, several neurological manifestations, such as headache, myalgia, malaise, fatigue, altered consciousness, agitation, anorexia, nausea, and vomiting, have been reported in patients with MPV. In addition, data from experimental studies have indicated that MPXV can gain access to the central nervous system (CNS) through the olfactory epithelium and infected circulatory monocytes/macrophages as two probable neuroinvasive mechanisms. Therefore, there are growing concerns about the long-term effect of MPXV on the CNS and subsequent neurological complications. This paper highlights the importance of the neuroinvasive potential of MPXV, coupled with neurological manifestations.

Exosome Derived from Human Neural Stem Cells Improves Motor Activity and Neurogenesis in a Traumatic Brain Injury Model.

Traumatic brain injury (TBI) is a leading cause of mortality and long-lasting disability globally. Although novel treatment options have been investigated, no effective therapeutic opportunities for TBI exist. Accumulating studies demonstrated that the paracrine mechanisms of stem cells may allow them to orchestrate regenerative processes after TBI. So far, very little attention has been paid to the beneficial effects of human neural stem cells (hNSCs) in comparison to their exosomes as a paracrine mechanism. This study is aimed at comparing the effect of hNSCs with their exosomes in a TBI model. For in vitro assessments, we cultured hNSCs using the neurosphere method and isolated hNSC-derived exosomes from culture supernatants. For in vivo experiments, male rats were divided into three groups (n = 8/group): TBI group: rats were subjected to a unilateral mild cortical impact; hNSC group: rats received a single intralesional injection of 2 × 106 hNSCs after TBI; and exosome group: rats received a single intralesional injection of 63 µg protein of hNSC-derived exosomes after TBI. Neurological assessments, neuroinflammation, and neurogenesis were performed at the predetermined time points after TBI. Our results indicated that the administration of exosomes improved the neurobehavioral performance measured by the modified neurological severity score (mNSS) on day 28 after TBI. Furthermore, exosomes inhibited the expression of reactive astrocytes as a key regulator of neuroinflammation marked by GFAP at the protein level, while enhancing the expression of Doublecortin (DCX) as a neurogenesis marker at the mRNA level. On the other hand, we observed that the expression of stemness markers (SOX2 and Nestin) was elevated in the hNSC group compared to the exosome and TBI groups. To sum up, our results demonstrated that the superior effects of exosomes versus parent hNSCs could be mediated by improving mNSS score and increasing DCX in TBI. Considerably, more work will need to be done to determine the beneficial effects of exosomes versus parent cells in the context of TBI.