Memory improvement in senile rats after prebiotic and probiotic supplementation is not induced by GLP-1.

INTRODUCTION: The mechanism underlying the memory improvement induced by prebiotic and probiotic supplementation remains unclear. Glucagon-like peptide type 1 (GLP-1) could play an important role since it is induced by prebiotics and enhances memory and learning. AIMS: We correlated the levels of GLP-1 with spatial memory in senile animals to determine its role in memory improvement after prebiotic and probiotic supplementation. METHODS: Senile rats were randomly assigned to four groups: (1) water (control); (2) Enterococcus faecium (probiotic); (3) agave inulin (prebiotic); and (4) E. faecium + agave inulin (symbiotic). Each supplement was administered by an orogastric cannula for 5 weeks. In the fifth week, spatial memory was assessed using the Morris Water Maze test (MWM). We extracted the hippocampus, intestine, and serum. GLP-1 levels were quantified by enzyme-linked immunosorbent assay. RESULTS: A significant decrease in escape latency time in the MWM was observed in all groups treated with supplements. The symbiotic group achieved the highest reduction (15.13 s ± 6.40) (p < 0.01). We did not find a significant increase in GLP-1 levels nor a direct correlation of its levels with spatial memory improvement (p > 0.05). CONCLUSION: Prebiotic and probiotic supplementation improved spatial memory in senile animals. However, this beneficial effect did not correlate with GLP-1 levels.

Copolymer-1 as a potential therapy for mild cognitive impairment.

Mild cognitive impairment (MCI) is a prodromal stage of memory impairment that may precede dementia. MCI is classified by the presence or absence of memory impairment into amnestic or non-amnestic MCI, respectively. More than 90% of patients with amnestic MCI who progress towards dementia meet criteria for Alzheimer's disease (AD). A combination of mechanisms promotes MCI, including intracellular neurofibrillary tangle formation, extracellular amyloid deposition, oxidative stress, neuronal loss, synaptodegeneration, cholinergic dysfunction, cerebrovascular disease, and neuroinflammation. However, emerging evidence indicates that neuroinflammation plays an important role in the pathogenesis of cognitive impairment. Unfortunately, there are currently no Food and Drug Administration (FDA)-approved drugs for MCI. Copolymer-1 (Cop-1), also known as glatiramer acetate, is a synthetic polypeptide of four amino acids approved by the FDA for the treatment of relapsing-remitting multiple sclerosis. Cop-1 therapeutic effect is attributed to immunomodulation, promoting a switch from proinflammatory to anti-inflammatory phenotype. In addition to its anti-inflammatory properties, it stimulates brain-derived neurotrophic factor (BDNF) secretion, a neurotrophin involved in neurogenesis and the generation of hippocampal long-term potentials. Moreover, BDNF levels are significantly decreased in patients with cognitive impairment. Therefore, Cop-1 immunization might promote synaptic plasticity and memory consolidation by increasing BDNF production in patients with MCI.

Spinal cord injury-induced cognitive impairment: a narrative review.

Spinal cord injury is a serious damage to the spinal cord that can lead to life-long disability. Based on its etiology, spinal cord injury can be classified as traumatic or non-traumatic spinal cord injury. Furthermore, the pathology of spinal cord injury can be divided into two phases, a primary injury phase, and a secondary injury phase. The primary spinal cord injury phase involves the initial mechanical injury in which the physical force of impact is directly imparted to the spinal cord, disrupting blood vessels, axons, and neural cell membranes. After the primary injury, a cascade of secondary events begins, expanding the zone of neural tissue damage, and exacerbating neurological deficits. Secondary injury is a progressive condition characterized by pro-inflammatory cytokines, reactive oxygen species, oxidative damage, excitatory amino acids such as glutamate, loss of ionic homeostasis, mitochondrial dysfunction, and cell death. This secondary phase lasts for several weeks or months and can be further subdivided into acute, subacute, and chronic. One of the most frequent and devastating complications developed among the spinal cord injury population is cognitive impairment. The risk of cognitive decline after spinal cord injury has been reported to be 13 times higher than in healthy individuals. The exact etiology of this neurological complication remains unclear, however, many factors have been proposed as potential contributors to the development of this disorder, such as concomitant traumatic brain injury, hypoxia, anoxia, autonomic dysfunction, sleep disorders such as obstructive sleep apnea, body temperature dysregulation, alcohol abuse, and certain drugs. This review focuses on a deep understanding of the pathophysiology of spinal cord injury and its relationship to cognitive impairment. We highlight the main mechanisms that lead to the development of this neurological complication in patients with spinal cord injury.

Effect of overweight and obesity on cognitive function in children from 8 to 12 years of age: a descriptive study with a cross-sectional design / Efecto del sobrepeso y la obesidad sobre la función cognitiva en niños de 8 a 12 años de edad: estudio descriptivo con diseño transversal

Introduction: overweight and obesity in childhood and adolescence have progressively increased in recent years. In addition to known comorbidities, obesity has been related to poor school performance at all ages, and is associated with cognitive impairment. Objective: to determine the difference in cognitive function between children from 8 to 12 years of age with normal weight, overweight, and obesity. Material and methods: an observational, cross-sectional study was carried out in 46 children from 8 to 12 years of age. Children were classified into 3 groups: normal-weight, overweight, and obese. Subsequently, cognitive function tests were performed. Results: the majority of obese children presented cognitive impairment (63 %; p = 0.02), with a greater degree of impairment compared to that observed in the other groups (80 %; p < 0.05). On the other hand, it was observed that children with overweight still have the possibility of avoiding the development of cognitive impairment if they change their habits, since the results of this group were similar to those found in the normal-weight group. Conclusions: we found a significant increase not only in cognitive impairment, but also in its degree of severity in obese children as compared to those with overweight or normal weight. (AU)

Introducción: el sobrepeso y la obesidad en la infancia y la adolescencia se han incrementado progresivamente durante los últimos años. Además de las comorbilidades conocidas, la obesidad se ha relacionado con un bajo rendimiento escolar en todas las edades, asociándose a alteraciones cognitivas. Objetivo: determinar la diferencia que existe en la función cognitiva de unos niños de 8 a 12 años con normopeso, sobrepeso u obesidad. Material y métodos: se realizó un estudio observacional y transversal en 46 niños de 8 a 12 años. Los niños se clasificaron en 3 grupos: normopeso, sobrepeso y obesidad. Posteriormente se realizaron pruebas de función cognitiva. Resultados: la mayoría de los niños con obesidad presentaron deterioro cognitivo (63 %; p = 0.02)), con mayor grado de deterioro en comparación con el observado en los demás grupos (80 %; p < 0.05). Por otro lado se observó que los niños con sobrepeso aún tienen posibilidad de evitar el desarrollo del padecimiento si corrigen sus hábitos, ya que los resultados de este grupo fueron similares a los del grupo con normopeso. Conclusiones: encontramos un incremento significativo no solo del déficit cognitivo sino también del grado de severidad de este en los niños obesos en comparación con aquellos con sobrepeso o normopeso. (AU)

Effect of overweight and obesity on cognitive function in children from 8 to 12 years of age: a descriptive study with a cross-sectional design.

INTRODUCTION: Introducción: el sobrepeso y la obesidad en la infancia y la adolescencia se han incrementado progresivamente durante los últimos años. Además de las comorbilidades conocidas, la obesidad se ha relacionado con un bajo rendimiento escolar en todas las edades, asociándose a alteraciones cognitivas. Objetivo: determinar la diferencia que existe en la función cognitiva de unos niños de 8 a 12 años con normopeso, sobrepeso u obesidad. Material y métodos: se realizó un estudio observacional y transversal en 46 niños de 8 a 12 años. Los niños se clasificaron en 3 grupos: normopeso, sobrepeso y obesidad. Posteriormente se realizaron pruebas de función cognitiva. Resultados: la mayoría de los niños con obesidad presentaron deterioro cognitivo (63 %; p = 0.02)), con mayor grado de deterioro en comparación con el observado en los demás grupos (80 %; p < 0.05). Por otro lado se observó que los niños con sobrepeso aún tienen posibilidad de evitar el desarrollo del padecimiento si corrigen sus hábitos, ya que los resultados de este grupo fueron similares a los del grupo con normopeso. Conclusiones: encontramos un incremento significativo no solo del déficit cognitivo sino también del grado de severidad de este en los niños obesos en comparación con aquellos con sobrepeso o normopeso.

INTRODUCCIÓN: Introduction: overweight and obesity in childhood and adolescence have progressively increased in recent years. In addition to known comorbidities, obesity has been related to poor school performance at all ages, and is associated with cognitive impairment. Objective: to determine the difference in cognitive function between children from 8 to 12 years of age with normal weight, overweight, and obesity. Material and methods: an observational, cross-sectional study was carried out in 46 children from 8 to 12 years of age. Children were classified into 3 groups: normal-weight, overweight, and obese. Subsequently, cognitive function tests were performed. Results: the majority of obese children presented cognitive impairment (63 %; p = 0.02), with a greater degree of impairment compared to that observed in the other groups (80 %; p < 0.05). On the other hand, it was observed that children with overweight still have the possibility of avoiding the development of cognitive impairment if they change their habits, since the results of this group were similar to those found in the normal-weight group. Conclusions: we found a significant increase not only in cognitive impairment, but also in its degree of severity in obese children as compared to those with overweight or normal weight.

Nelson Syndrome: A Case Report and Literature Review.

OBJECTIVE: Nelson syndrome (NS) is a rare clinical disorder that can occur after total bilateral adrenalectomy (TBA), performed as a treatment for Cushing disease. NS is defined as the accelerated growth of an adrenocorticotropic hormone-producing pituitary adenoma. Our objective is to describe a case of NS and discuss it based on existing knowledge of this syndrome. METHODS: We describe the case of a woman diagnosed with NS at our facility in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran and review published cases of NS. RESULTS: The patient, a 35-year-old woman with Cushing disease, had been diagnosed in 2006 at the endocrinology department in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. In 2007, a laparoscopic TBA was performed, and 2 years later, she presented with hyperpigmentation and adrenocorticotropic hormone levels of up to 11 846 pg/mL. NS was suspected, and as magnetic resonance imaging showed macroadenoma, transsphenoidal surgery was performed. The patient remained asymptomatic until 2012, when she presented with a right hemicranial headache, photophobia, and phonophobia. A fresh magnetic resonance imaging was performed, which documented tumor growth. She was referred to the Instituto Nacional de Neurologia y Neurocirugia, where she underwent surgery. CONCLUSION: NS develops as a complication of TBA, which is used as a treatment of Cushing disease. The main treatment is surgery and radiotherapy.

[A septal rupture of atypical location after myocardial infarction. A clinical case]. / Ruptura septal de localización atípica posterior a infarto del miocardio. Caso clínico

Paciente masculino de 46 años de edad con antecedentes personales de hipertensión arterial sistémica, tabaquismo y etilismo y heredofamiliares de hipertensión arterial sistémica. El padecimiento inició con cuadro de astenia, adinamia, disnea progresiva, edema de miembros inferiores y aumento del volumen abdominal, por lo que acudió con el médico, quien decidió hospitalizarlo. El paciente recibió tratamiento médico con captopril, furosemida y espironolactona, sin mejoría de los síntomas, motivo por el cual se lo refirió a la institución de los autores. Al llegar al servicio de urgencias, el sujeto se encontraba estable.

Immunization with neural-derived peptides increases neurogenesis in rats with chronic spinal cord injury.

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.

Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord 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.

Stand alone or join forces? Stem cell therapy for stroke.

INTRODUCTION: Stroke is a major cause of mortality and disability with a narrow therapeutic window. Stem cell therapy may enhance the stroke recovery. AREAS COVERE: Regenerative medicine via stem cells stands as a novel therapy for stroke. In particular, bone marrow-derived mesenchymal stem cells (MSCs) have neuroprotective and anti-inflammatory properties that improve brain function after stroke. Here, we discuss the safety, efficacy, and mechanism of action underlying the therapeutic effects of bone marrow-derived MSCs. We also examine the discrepant transplant protocols between preclinical studies and clinical trials. Laboratory studies show the safety and efficacy of bone marrow-derived MSCs in stroke models. However, while safe, MSCs remain to be fully evaluated as effective in clinical trials. Furthermore, recognizing the multiple cell death processes associated with stroke, we next discuss the potential therapeutic benefits of a combination therapy. With preliminary results and on-going clinical trials, a careful assessment of dosing, timing, and delivery route regimens will further direct the future of stem cell therapy for neurological disorders, including stroke. EXPERT OPINION: Bone marrow-derived MSCs appear to be the optimal stem cell source for stroke therapy. Optimizing dosing, timing, and delivery route should guide the clinical application of bone marrow-derived MSCs.