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-1β) 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-1β 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.

Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue.

The recent developments in the management of spinal cord injury (SCI) have led to a reduction in mortality and in the consequences, resulting from incomplete spinal cord damage in those who survive. In this respect, it is noteworthy that SCI not only results in paraplegia or tetraplegia, but also in systemic, cardiovascular and metabolic alterations secondary to autonomic dysfunction. After SCI there is a decrease in sympathetic discharge and an increase in parasympathetic drive, resulting in profound changes in arterial blood pressure and heart rate. When SCI is induced in experimental animals, an immediate hypotension occurs (acute phase) which has been attributed to an autonomic imbalance involving a predominance of parasympathetic activity. Subsequently, an episodic hypertension may develop (chronic phase) as a part of a condition denominated autonomic dysreflexia. This hypertension is caused by afferent stimulation below the level of injury and can be so severe that sometimes may lead to cerebral haemorrhage, seizures, and death. In the light of the above lines of evidence, experimental SCI may provide an ideal model to study the nature of cardiovascular mechanisms following traumatic injury. Thus, the present review will deal with an update of the possible cardiovascular complications associated to SCI (including spinal shock, autonomic dysreflexia, deep venous thrombosis, and risk for coronary heart disease). This will be discussed within the context of the development of drugs with potential therapeutic usefulness in the acute and chronic stages of SCI.

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After damage to the central nervous system (CNS) the body is protected by an adaptive immune response which is directed against myelin-associated proteins. Active immunization with nonpathogenic derivatives of CNS-associated peptides (DCAP) reduces the degeneration of neurons and promotes motor recovery after spinal cord injury (SCI) in rats. In order to improve even more the neurological outcome obtained with this therapy, either a combination of DCAP immunization plus glutathione monoethyl ester (GSHE) or a double DCAP immunization were performed. GSHE is a cell-permeant derivative of glutathione, a potent antioxidant agent that significantly inhibits lipid peroxidation after SCI. After a contusive or compressive SCI, the combination of GSHE + DCAP immunization, induced better motor recovery, a higher number of myelinated axons and better rubrospinal neuron survival than immunization alone. On the other hand, double-DCAP immunization counteracted the protective effect of DCAP therapy. Motor recovery and neuronal survival of double-immunized rats were similar to those observed in control animals (PBS-treated). Further studies revealed that double immunization was not encephalitogenic but inhibited the proliferative response of T-cells specific to the DCAP-immunized peptide. This clonal dysfunction was probably secondary to anergy. GSHE improves the protective effect induced by DCAP immunization while double immunization, reverts it.

The myelin-associated protein Nogo-A has received more research attention than any other inhibitor of axonal regeneration in the injured central nervous system (CNS). Circumvention of its inhibitory effect, by using antibodies specific to Nogo-A, has been shown to promote axonal regrowth. Studies in our laboratory have demonstrated that active or passive immunization of CNS-injured rats or mice with myelin-associated peptides induces a T-cellmediated protective autoimmune response, which promotes recovery by reducing posttraumatic degeneration. Here, we show that neuronal degeneration after incomplete spinal-cord contusion in rats was substantially reduced, and hence recovery was significantly promoted, by posttraumatic immunization with p472, a peptide derived from Nogo-A. The observed effect seemed to be mediated by T cells and could be reproduced by passive transfer of a T cell line directed against the Nogo-A peptide. Thus, it seems that after incomplete spinal-cord injury, immunization with a variety of myelin-associated peptides, including those derived from Nogo-A, can be used to evoke a T cell-mediated response that promotes recovery. The choice of peptide(s) for clinical treatment of spinalcord injuries should be based on safety considerations; in particular, the likelihood that the chosen peptide will not cause an autoimmune disease or interfere with essential functions of this peptide or other proteins. From a therapeutic point of view, the fact that the active cellular agents are T cells rather than antibodies is an advantage, as T cell production commences within the time window required for a protective effect after spinal-cord injury, whereas antibody production takes longer.