Stabilization of V1 interneuron-motor neuron connectivity ameliorates motor phenotype in a mouse model of ALS.

Loss of connectivity between spinal V1 inhibitory interneurons and motor neurons is found early in disease in the SOD1G93A mice. Such changes in premotor inputs can contribute to homeostatic imbalance of motor neurons. Here, we show that the Extended Synaptotagmin 1 (Esyt1) presynaptic organizer is downregulated in V1 interneurons. V1 restricted overexpression of Esyt1 rescues inhibitory synapses, increases motor neuron survival, and ameliorates motor phenotypes. Two gene therapy approaches overexpressing ESYT1 were investigated; one for local intraspinal delivery, and the other for systemic administration using an AAV-PHP.eB vector delivered intravenously. Improvement of motor functions is observed in both approaches, however systemic administration appears to significantly reduce onset of motor impairment in the SOD1G93A mice in absence of side effects. Altogether, we show that stabilization of V1 synapses by ESYT1 overexpression has the potential to improve motor functions in ALS, demonstrating that interneurons can be a target to attenuate ALS symptoms.

Tetralogy of Fallot: Hypoxia, the villain of the story?

BACKGROUND: Tetralogy of Fallot (ToF) is a cyanotic congenital heart disease, composed of four malformations: persistent communication between the right and the left ventricle, pulmonary stenosis, overriding aorta, and right ventricle hypertrophy. The etiology of this disease is not entirely known as yet, but it has been proposed that the pathology has genetic components. During embryonic development, the fetus is exposed to a physiological hypoxia to facilitate the formation of blood vessels and blood cells through de novo processes. METHODS: After researching scientific databases on the implications of oxygen on the normal and abnormal development of organs, especially the heart, we were able to propose that oxygen deprivation may be the cause of the disease. RESULTS: During this period, the hypoxia-inducible factor is activated and triggers transcriptional responses that enable adaptation to the hypoxic environment through angiogenic activation. High levels of this protein can alter certain physiological pathways, such as those related to the vascular endothelial growth factor. Research has shown that prolonged oxygen deprivation during embryological development can lead to the occurrence of congenital heart diseases, such as ToF. CONCLUSIONS: Studies using animal models have demonstrated that the deficiency or disruption of a protein called "CITED2," which plays an important role in cardiac morphogenesis and its loss, results in the alteration of pluripotent, cardiac, and neural lineage differentiation, thereby disrupting the normal development of the heart and other tissues.

Epilepsia y quemados: Descripción de casos

La epilepsia es uno de los trastornos neurológicos más frecuentes a nivel mundial y afecta a más de 70 millones de personas en todo el mundo, las quemaduras son eventos traumáticos que representan un importante problema de salud pública. Método: Se realizó un estudio descriptivo de corte transversal, se incluyeron pacientes con quemaduras secundarias a eventos convulsivos, en un hospital de Bogotá, Colombia entre agosto de 2019 y diciembre de 2020, con el objetivo de describir la frecuencia y características de las quemaduras secundarias a un evento convulsivo en esta población. Resultados: La mayoría de los casos se presentó en mujeres solteras (65%) con una edad promedio de 44 años provenientes en su mayoría de zona urbana (70%), con ocupación principal ama de casa (45%), el principal desencadenante de la crisis epiléptica fue la mala adherencia al tratamiento (70%), el 95% de los pacientes no tuvo un control previo por neurología y el área corporal más afectada fue las extremidades superiores (brazos) en el 55%, la estancia hospitalaria promedio fue de 20 días en Unidad de Cuidados Intensivos. Conclusión: La epilepsia es una enfermedad prevalente, una baja adherencia a la medicación y un inadecuado seguimiento neurológico pueden llevar a problemas graves como las quemaduras, con la consecuente afectación de la calidad de vida de los pacientes y estancias en UCI prolongadas, así como secuelas importantes que imposibiliten la reincorporación laboral de la persona, convirtiéndose en un problema de salud pública.

Epilepsy is one of the most common neurological disorders worldwide, affecting more than 70 million people worldwide; on the other hand, burns are traumatic events that represent an important public health problem. Considering the relationship that has been documented between epilepsy and burns, a descriptive cross-sectional study was carried out in the burn unit of a tertiary care hospital in the city of Bogotá, Colombia. 78 medical records were reviewed, 20 correspond to patients burned during a convulsive episode, most of the cases occurred in single women (65%) with an average age of 44 years, mostly from urban areas (70%), with main occupation housewife (45%), the main trigger of the epileptic crisis was poor adherence to treatment (70%), 95% of the patients did not have a previous control by neurology and the body area most affected was the upper limbs (arms) in 55%, the average hospital stay was 20 days in the Intensive Care Unit. Epilepsy is a disease with poor adherence to medication and inadequate neurological follow-up that may be related to the presence of convulsive episodes, which can lead to serious problems such as burns, with the consequent impact on the quality of life of patients. as well as important consequences that make it impossible for the person to return to work, becoming a public health problem.