Motor Recovery after Chronic Spinal Cord Transection in Rats: A Proof-of-Concept Study Evaluating a Combined Strategy.

BACKGROUND: The chronic phase of Spinal Cord (SC) injury is characterized by the presence of a hostile microenvironment that causes low activity and a progressive decline in neurological function; this phase is non-compatible with regeneration. Several treatment strategies have been investigated in chronic SC injury with no satisfactory results. OBJECTIVE- In this proof-of-concept study, we designed a combination therapy (Comb Tx) consisting of surgical glial scar removal plus scar inhibition, accompanied with implantation of mesenchymal stem cells (MSC), and immunization with neural-derived peptides (INDP). METHODS: This study was divided into three subsets, all in which Sprague Dawley rats were subjected to a complete SC transection. Sixty days after injury, animals were randomly allocated into two groups for therapeutic intervention: control group and animals receiving the Comb-Tx. Sixty-three days after treatment we carried out experiments analyzing motor recovery, presence of somatosensory evoked potentials, neural regeneration-related genes, and histological evaluation of serotoninergic fibers. RESULTS: Comb-Tx induced a significant locomotor and electrophysiological recovery. An increase in the expression of regeneration-associated genes and the percentage of 5-HT+ fibers was noted at the caudal stump of the SC of animals receiving the Comb-Tx. There was a significant correlation of locomotor recovery with positive electrophysiological activity, expression of GAP43, and percentage of 5-HT+ fibers. CONCLUSION: Comb-Tx promotes motor and electrophysiological recovery in the chronic phase of SC injury subsequent to a complete transection. Likewise, it is capable of inducing the permissive microenvironment to promote axonal regeneration.

Probiotics and Prebiotics as a Therapeutic Strategy to Improve Memory in a Model of Middle-Aged Rats.

Aging is associated with morphological, physiological and metabolic changes, leading to multiorgan degenerative pathologies, such as cognitive function decline. It has been suggested that memory loss also involves a decrease in neurotrophic factors, including brain-derived neurotrophic factor (BDNF). In recent years, microbiota has been proposed as an essential player in brain development, as it is believed to activate BDNF secretion through butyrate production. Thus, microbiota modulation by supplementation with probiotics and prebiotics may impact cognitive decline. This study aimed to evaluate the effects of probiotics and prebiotics supplementation on the memory of middle-aged rats. Sprague-Dawley male rats were randomized in four groups (n = 13 per group): control (water), probiotic (E. faecium), prebiotic (agave inulin), symbiotic (E. faecium + inulin), which were administered for 5 weeks by oral gavage. Spatial and associative memory was analyzed using the Morris Water Maze (MWM) and Pavlovian autoshaping tests, respectively. Hippocampus was obtained to analyze cytokines [interleukin (IL-1ß) and tumor necrosis factor (TNF-α)], BDNF and γ-aminobutyric acid (GABA) by enzyme-linked immunosorbent assay (ELISA). Butyrate concentrations were also evaluated in feces. The symbiotic group showed a significantly better performance in MWM (p < 0.01), but not in Pavlovian autoshaping test. It also showed significantly lower concentrations of pro-inflammatory cytokines (p < 0.01) and the reduction in IL-1ß correlated with a better performance of the symbiotic group in MWM (p < 0.05). Symbiotic group also showed the highest BDNF and butyrate levels (p < 0.0001). Finally, we compared the electrophysiological responses of control (n = 8) and symbiotic (n = 8) groups. Passive properties of CA1 pyramidal cells (PCs) exhibited changes in response to the symbiotic treatment. Likewise, this group showed an increase in the N-methyl-D-aspartate receptor (NMDA)/AMPA ratio and exhibited robust long-term potentiation (LTP; p < 0.01). Integrated results suggest that symbiotics could improve age-related impaired memory.

Menstrual Blood-Derived Stem Cells: In Vitro and In Vivo Characterization of Functional Effects.

Accumulating evidence has demonstrated that menstrual blood stands as a viable source of stem cells. Menstrual blood-derived stem cells (MenSCs) are morphologically and functionally similar to cells directly extracted from the endometrium, and present dual expression of mesenchymal and embryonic cell markers, thus becoming interesting tools for regenerative medicine. Functional reports show higher proliferative and self-renewal capacities than bone marrow-derived stem cells, as well as successful differentiation into hepatocyte-like cells, glial-like cells, endometrial stroma-like cells, among others. Moreover, menstrual blood stem cells may be used with increased efficiency in reprogramming techniques for induced Pluripotent Stem cell (iPS) generation. Experimental studies have shown successful treatment of stroke, colitis, limb ischemia, coronary disease, Duchenne's muscular atrophy and streptozotocin-induced type 1 diabetes animal models with MenSCs. As we envision an off-the-shelf product for cell therapy, cryopreserved MenSCs appear as a feasible clinical product. Clinical applications, although still very limited, have great potential and ongoing studies should be disclosed in the near future.

Menstrual blood transplantation for ischemic stroke: Therapeutic mechanisms and practical issues.

Cerebrovascular diseases are a major cause of death and long-term disability in developed countries. Tissue plasmin activator (tPA) is the only approved therapy for ischemic stroke, strongly limited by the short therapeutic window and hemorrhagic complications, therefore excluding most patients from its benefits. The rescue of the penumbra area of the ischemic infarct is decisive for functional recovery after stroke. Inflammation is a key feature in the penumbra area and it plays a dual role, improving injury in early phases but impairing neural survival at later stages. Stem cells can be opportunely used to modulate inflammation, abrogate cell death and, therefore, preserve neural function. We here discuss the possible role of stem cells derived from menstrual blood as restorative treatment for stroke. We highlight the availability, proliferative capacity, pluripotentiality and angiogenic features of these cells and explore their present and future experimental and clinical applications.