Spinal cord injury (SCI) is a disabling neurological disorder that causes neural circuit dysfunction. Although various therapies have been applied to improve the neurological outcomes of SCI, little clinical progress has been achieved. Stem cell–based therapy aimed at restoring the lost cells and supporting micromilieu at the site of the injury has become a conceptually attractive option for tissue repair following SCI. Adult human neural stem/progenitor cells (hNS/PCs) were obtained from the epileptic human brain specimens. Induction of SCI was followed by the application of lentiviral vector-mediated green fluorescent protein–labeled hNS/PCs seeded in PuraMatrix peptide hydrogel (PM). The co-application of hNS/PCs and PM at the SCI injury site significantly enhanced cell survival and differentiation, reduced the lesion volume, and improved neurological functions compared to the control groups. Besides, the transplanted hNS/PCs seeded in PM revealed significantly higher migration abilities into the lesion site and the healthy host tissue as well as a greater differentiation into astrocytes and neurons in the vicinity of the lesion as well as in the host tissue. Our data suggest that the transplantation of hNS/PCs seeded in PM could be a promising approach to restore the damaged tissues and improve neurological functions after SCI.
Various neurotrophins (NTs), including nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4, promote cellular differentiation, survival, and maintenance, as well as synaptic plasticity, in the peripheral and central nervous system. The function of microRNAs (miRNAs) and other small non-coding RNAs, as regulators of gene expression, is pivotal for the appropriate control of cell growth and differentiation. There are positive and negative loops between NTs and miRNAs, which exert modulatory effects on different signaling pathways. The interplay between NTs and miRNAs plays a crucial role in the regulation of several physiological and pathological brain procedures. Emerging evidence suggests the diagnostic and therapeutic roles of the interactions between NTs and miRNAs in several neuropsychological disorders, including epilepsy, multiple sclerosis, Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, schizophrenia, anxiety disorders, depression, post-traumatic stress disorder, bipolar disorder, and drug abuse. Here, we review current data regarding the regulatory interactions between NTs and miRNAs in neuropsychological disorders, for which novel diagnostic and/or therapeutic strategies are emerging. Targeting NTs-miRNAs interactions for diagnostic or therapeutic approaches needs to be validated by future clinical studies.
Background Several studies on gamma-irradiated influenza A virus (γ-Flu) have revealed its superior efficacy for inducing homologous and heterologous virus-specific immunity. However, many inactivated vaccines, notably in nasal delivery, require adjuvants to increase the quality and magnitude of vaccine responses. Methods To illustrate the impacts of co-administration of the gamma-irradiated H1N1 vaccine with poly (I:C) and recombinant murine CCL21, either alone or in combination with each other, as adjuvants on the vaccine potency, mice were inoculated intranasally 3 times at one-week interval with γ-Flu alone or with any of the three adjuvant combinations and then challenged with a high lethal dose (10 LD50) of A/PR/8/34 (H1N1) influenza virus. Virus-specific humoral, mucosal, and cell-mediated immunity, as well as cytokine profiles in the spleen (IFN-γ, IL-12, and IL-4), and in the lung homogenates (IL-6 and IL-10) were measured by ELISA. The proliferative response of restimulated splenocytes was also determined by MTT assay. Results The findings showed that the co-delivery of the γ-Flu vaccine and CCL21 or Poly (I:C) significantly increased the vaccine immunogenicity compared to the non-adjuvanted vaccine, associated with more potent protection following challenge infection. However, the mice given a combination of CCL21 with poly (I:C) had strong antibody- and cell-mediated immunity, which were considerably higher than responses of mice receiving the γ-Flu vaccine with each adjuvant separately. This combination also reduced inflammatory mediator levels (notably IL-10) in lung homogenate samples. Conclusions The results indicate that adjuvantation with the CCL21 and poly (I:C) can successfully induce vigorous vaccine-mediated protection, suggesting a robust propensity for CCL21 plus poly (I:C) as a potent mucosal adjuvant.
A growing number of studies indicate a broad range of neurological manifestations, including seizures, occur in patients with COVID‐19 infection. We report a 29‐year‐old female patient with status epilepticus and positive SARS‐CoV‐2 in the cerebrospinal fluid. Our findings support previous reports suggesting seizure as a possible symptom of COVID‐19 infection.
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