Aims
Immunization with neural‐derived peptides (INDP) has demonstrated to be a promising therapy to achieve a regenerative effect in the chronic phase of the spinal cord injury (SCI). Nevertheless, INDP‐induced neurogenic effects in the chronic stage of SCI have not been explored.
Methods and Results
In this study, we analyzed the effect of INDP on both motor and sensitive function recovery; afterward, we assessed neurogenesis and determined the production of cytokines (IL‐4, IL‐10, and TNF alpha) and neurotrophic factors (BDNF and GAP‐43). During the chronic stage of SCI, rats subjected to INDP showed a significant increase in both motor and sensitive recovery when compared to the control group. Moreover, we found a significant increase in neurogenesis, mainly at the central canal and at both the dorsal and ventral horns of INDP‐treated animals. Finally, INDP induced significant production of antiinflammatory and regeneration‐associated proteins in the chronic stages of SCI.
Conclusions
These findings suggest that INDP has a neurogenic effect that could improve motor and sensitive recovery in the chronic stage of SCI. Moreover, our results also envision the use of INDP as a possible therapeutic strategy for other trauma‐related disorders like traumatic brain injury.
Immunization with neural derived peptides (INDP), as well as scar removal (SR) and the use of matrices with bone marrow-mesenchymal stem cells (MSCs), have been studied separately and proven to induce a functional and morphological improvement after spinal cord injury (SCI). Herein, we evaluated the therapeutic effects of INDP combined with SR and a fibrin glue matrix (FGM) with MSCs (FGM-MSCs), on motor recovery, axonal regeneration-associated molecules and cytokine expression, axonal regeneration (catecholaminergic and serotonergic fibers), and the induction of neurogenesis after a chronic SCI. For this purpose, female adult Sprague-Dawley rats were subjected to SCI, 60 days after lesion, rats were randomly distributed in four groups: (1) Rats immunized with complete Freund's adjuvant + PBS (vehicle; PBS-I); (2) Rats with SR+ FGM-MSCs; (3) Rats with SR+ INDP + FGM-MSCs; (4) Rats only with INDP. Afterwards, we evaluated motor recovery using the BBB locomotor test. Sixty days after the therapy, protein expression of TNFα, IL-4, IL-10, BDNF, and GAP-43 were evaluated using ELISA assay. The number of catecholaminergic and serotonergic fibers were also determined. Neurogenesis was evaluated through immunofluorescence. The results show that treatment with INDP alone significantly increased motor recovery, anti-inflammatory cytokines, regeneration-associated molecules, axonal regeneration, and neurogenesis when compared to the rest of the groups. Our findings suggest that the combination therapy (SR + INDP + FGM-MSCs) modifies the non-permissive microenvironment post SCI, but it is not capable of inducing an appropriate axonal regeneration or neurogenesis when compared to the treatment with INDP alone.
Introduction: COVID-19 hospitalizations and deaths have raised the need of identifying prognostic factors for medical decision-making. Methods: Observational, retrospective study analyzing 191 COVID-19 patients' serum inflammatory biomarkers. Results: The median age was 48.7 ± 12.7 years, 75.9% being men. Overweight/obesity was the most common comorbidity in 83.8% of patients. 44.5% had moderate disease followed by 43.5% with severe disease. The mean percentage of pulmonary damage was 53.4% ± 28.7. Serum leukocyte-to-lymphocyte ratio >7.7, neutrophil-to-lymphocyte ratio >10, platelet-to-lymphocyte ratio ≥250 and nutritional index <362 all were independent mortality predictors for COVID-19. Conclusions: A leukocyte-to-lymphocyte ratio >7.7 as well as a nutritional index <362 at hospitalization were independently associated with an increased mortality.
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