Targeting microRNAs involved in the BDNF signaling impairment in neurodegenerative diseases

Neurodegenerative diseases are becoming an ever-increasing problem in aging populations. Low levels of brain-derived neurotrophic factor (BDNF) have previously been associated with the pathogenesis of numerous neurodegenerative diseases. Recently, microRNAs (miRNAs) have been proposed as potential novel therapeutic targets for treating various diseases of the central nervous system (CNS), and interestingly, few studies have reported several miRNAs that downregulate the expression levels of BDNF. However, substantial challenges exist when attempting to translate these findings into practical anti-miRNA therapeutics, especially when the targets remain inside the CNS. Thus, in this review, we summarize the specific molecular mechanisms by which several miRNAs negatively modulate the expressions of BDNF, address the potential clinical difficulties that can be faced during the development of anti-miRNA-based therapeutics and propose strategies to overcome these challenges.

Deficit of quantal release of GABA in experimental models of temporal lobe epilepsy

Because GABA (gamma-aminobutyric acid) receptor-mediated inhibition controls the excitability of principal neurons in the brain, deficits in GABAergic inhibition have long been favored to explain seizures. In an experimental model of temporal lobe epilepsy, we have identified a deficit of inhibition in presynaptic GABAergic terminals characterized by decreased GABA quantal activity associated with reduced synaptic vesicle density. This decrease in vesicle number primarily seems to affect the reserve pool, rather than the docked or the readily releasable pool.

Unmasking of the trigemino-accessory reflex in accessory facial anastomosis

To evaluate the possible blink reflex responses in facial muscles reinnervated by the accessory nerve. Method: Eleven patients with a complete facial palsy were submitted to a surgical repair by an accessory facial nerve anastomosis (AFA). In this pathological group, blink reflex was studied by means of percutaneous electrical stimulation of the supraorbital nerve and recording from the orbicularis oculi muscle. A control group comprised seven normal people and seven patients with a complete Bell's facial palsy; in this group, responses on the sternocleidomastoideus (SCM) muscles were studied after supraorbital nerve stimulation. Results: All the patients with AFA showed a consistent degree of facial reinnervation. Ten out of the 11 patients with AFA showed reflex responses; in six, responses were configured by a double component pattern, resembling the R1 and R2 components of the blink reflex; three patients had an R1-like response and one patient showed a unique R2 component. Mean values of latencies were 15.2 (SD 4.6) ms for the R1 and 85.3 (SD 9.6) ms for the R2. In the control group, eight out of 14 people had evidence of reflex responses in the SCM muscles; these were almost exclusively configured by a bilateral late component (mean latency 63.5 (SD 15.9) ms) and only one of the subjects showed an early response at 11 ms. Conclusion: The trigemino-accessory reflex response in the pathological group was more complex and of a significantly higher incidence than in the control group. These differences could be tentatively explained by a mechanism of synaptic plasticity induced by the impairment of the efferent portion of the reflex. This could unmask the central linking between the trigeminal and the accessory limbs of the reflex. The findings described could be a demonstration of neurobionomic function in the repairing process of the nervous system.

Infection of the central nervous system by Mycobacterium tuberculosis in patients infected with human immunodeficiency virus (the new neurotuberculosis)

Neurologic complications of HIV infection are numerous. This review focuses on the clinical presentation, diagnostic particularities and therapeutic issues of neurotuberculosis. The pertinent literature describing this important infection is succinctly summarized with a particular emphasis on the discussion of differences in clinical presentation between HIV-infected and -uninfected patients.

Valor pronóstico del incremento de la tensión arterial sistólica con el ejercicio en pacientes hipertensos con enfermedad coronaria conocida o sospechada.

La asociación entre un incremento exagerado de la presión arterial sistólica con el ejercicio (IEPASE) y la probabilidad de eventos cardiovasculares es controvertida. Nuestro propósito fue determinar la posible asociación de un IEPASE con la supervivencia y con el riesgo de eventos cardíacos graves en pacientes hipertensos con enfermedad coronaria conocida o sospechada. Se trata de un estudio retrospectivo y observacional sobre una muestra de 5.226 pacientes con historia de hipertensión arterial y enfermedad coronaria conocida o sospechada referidos a ecocardiografía de ejercicio. El IEPASE se definió como un incremento de la presión arterial sistólica con el ejercicio igual o superior al percentil 95 de esta población (80 mmHg). Los objetivos fueron mortalidad total, mortalidad de origen cardíaco e infarto de miocardio (IM). En un seguimiento medio de 4,7 años, se registraron 978 muertes (371 de origen cardíaco) y 798 IM. Las tasas anuales de mortalidad, mortalidad de origen cardíaco e IM fueron del 2,73; 0,83 y 2,63% en pacientes con IEPASE y de 4,4; 1,58 y 3,98%, respectivamente en aquellos sin IEPASE (p < 0,001; p = 0,012 y p = 0,014, respectivamente). Tras un ajuste multivariado, el IEPASE resultó predictor de mortalidad por cualquier causa (HR: 0,70; IC 95%: 0,52-0,95; p = 0,023) e IM (HR: 0,69; IC 95%: 0,50-0,95; p = 0,022), pero la asociación con mortalidad cardiaca no alcanzó significación estadística (HR: 0,72; IC 95%: 0,43-1,20; p = 0,2). El IEPASE se asoció con mayor probabilidad de supervivencia y menor riesgo de IM en pacientes hipertensos con enfermedad coronaria conocida o sospechada.