Efectos de la hipertensión arterial en el plexo coroideo, la composición del líquido cefalorraquídeo y su relación con ciertos tipos de demencia

El plexo coroideo es una estructura muy vascularizada que se localiza en los ventrículos laterales y que clásicamente ha sido relacionada con la formación del líquido cefalorraquídeo (LCR), sin embargo, realiza funciones importantes como la secreción de proteínas y participar en procesos de aclaramiento de sustancias desde el LCR a las sangre o viceversa, formando parte de la barrera sangre-líquido cefalorraquídeo (BSLCR). Utilizando técnicas inmunohistoquímicas, Western-Blot, electroforesis bidimensional, MALDI-TOF y doppler transcraneal, se han estudiado los efectos de la HTA en la hemodinámica cerebral de ratas SHR (rata espontáneamente hipertensa), en la morfología y funcionamiento del plexo coroideo, en la integridad de la BSLCR, en la composición del LCR y en la estructura de los vasos sanguíneos. Además se han estudiado los efectos de la HTA sobre el plexo coroideo en cuanto al aclaramiento del cerebro del beta-amiloide y su posible implicación en el desarrollo de la enfermedad de Alzheimer (EA) como factor de riesgo. También se estudia morfológica y funcionalmente el plexo coroideo en un modelo de ratón transgénico (3xTg AD) que expresa tres mutaciones relacionadas con la enfermedad de Alzheimer (PS1KI (M146L) x PPA (mutación Swedish K670N y M671L) x TAU (P301L)

Papel de la eminencia talámica, el sistema olfativo principal y el sistema olfativo accesorio en la maduración sexual del encéfalo y las manifestaciones clínico-morfológicas del síndrome de Kallmann

El desarrollo de sistema olfativo y la diferenciación sexual del encéfalo, tanto en el hombre como en los animales, están estrechamente relacionados. Actualmente, se describe la imbricación entre la formación del sistema olfativo principal y la migración de las neuronas que sintetizan la hormona liberadora de gonadotrofinas (GnRF). Estas neuronas GnRF se desplazan por los nervios olfatorios, desde la parte medial del epitelio nasal al bulbo olfatorio, continúan por el encéfalo rostral hasta alcanzar el hipotálamo anterior. Por otro lado, el síndrome de Kallmann es un trastorno genético en el cual se combina el hipogonadismo hipogonadotrópico y la anosmia. El hipogonadismo se caracteriza por la ausencia o reducción de los niveles de hormona liberadora de gonadotrofinas y la anosmia la aplasia del bulbo olfatorio. En esta revisión se analizan las estructuras responsables de la maduración del sistema olfativo principal y accesorio, la diferenciación sexual del encéfalo y su relación con todas las manifestaciones clínicas y morfológicas del síndrome Kallmann. The olfactory system development and brain sexual maturation, in man and animals, are closely related. Currently the overlap between the formation of the olfactory system and the migration of neurons that synthesize gonadotropin-releasing hormone (GnRF) are described. The GnRF neurons migrate from the medial portion of the nasal epithelium through the olfactory nerves and the main olfactory bulb to the anterior hypothalamus. Furthermore, Kallmann syndrome (KS) is a genetic disorder in which combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is characterized by the absence or reduced levels of gonadotropin-releasing hormone and anosmia is due to aplasia of the olfactory bulb. The basic clinical manifestations of KS are: anosmia and the absence of puberty. The structures responsible for the maturation of the main and accessory olfactory systems, the sexual differentiation of the brain and its relationship with all the clinical manifestations of Kallmann syndrome are analyzed in this revie

Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer's disease

Compromised secretory function of choroid plexus (CP) and defective cerebrospinal fluid (CSF) production, along with accumulation of beta-amyloid (Aβ) peptides at the blood-CSF barrier (BCSFB), contribute to complications of Alzheimer's disease (AD). The AD triple transgenic mouse model (3xTg-AD) at 16 month-old mimics critical hallmarks of the human disease: β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) with a temporal- and regional- specific profile. Currently, little is known about transport and metabolic responses by CP to the disrupted homeostasis of CNS Aβ in AD. This study analyzed the effects of highly-expressed AD-linked human transgenes (APP, PS1 and tau) on lateral ventricle CP function. Confocal imaging and immunohistochemistry revealed an increase only of Aβ42 isoform in epithelial cytosol and in stroma surrounding choroidal capillaries; this buildup may reflect insufficient clearance transport from CSF to blood. Still, there was increased expression, presumably compensatory, of the choroidal Aβ transporters: the low density lipoprotein receptor-related protein 1 (LRP1) and the receptor for advanced glycation end product (RAGE). A thickening of the epithelial basal membrane and greater collagen-IV deposition occurred around capillaries in CP, probably curtailing solute exchanges. Moreover, there was attenuated expression of epithelial aquaporin-1 and transthyretin (TTR) protein compared to Non-Tg mice. Collectively these findings indicate CP dysfunction hypothetically linked to increasing Aβ burden resulting in less efficient ion transport, concurrently with reduced production of CSF (less sink action on brain Aβ) and diminished secretion of TTR (less neuroprotection against cortical Aβ toxicity). The putative effects of a disabled CP-CSF system on CNS functions are discussed in the context of AD

International lower limb collaborative (INTELLECT) study: a multicentre, international retrospective audit of lower extremity open fractures

Trauma remains a major cause of mortality and disability across the world1, with a higher burden in developing nations2. Open lower extremity injuries are devastating events from a physical3, mental health4, and socioeconomic5 standpoint. The potential sequelae, including risk of chronic infection and amputation, can lead to delayed recovery and major disability6. This international study aimed to describe global disparities, timely intervention, guideline-directed care, and economic aspects of open lower limb injuries

Early Regressive Development of the Subcommissural Organ of Two Human Fetuses with Non-Communicating Hydrocephalus

Hydrocephalus is a central nervous system condition characterized by CSF buildup and ventricular hypertrophy. It is divided into two types: communicative and non-communicating hydrocephalus. Congenital hydrocephalus has been linked to several changes in the subcommissural organ (SCO). However, it is unclear whether these changes occur before or as a result of the hydrocephalic illness. This report presents three cases of human fetuses with hydrocephalus: one non-communicating case, two communicating cases, and two controls. Hematoxylin–Eosin (H&E) or cresyl violet and immunohistochemistry with anti-transthyretin were used to analyze SCO morphological and secretory changes. We conclude that in the cases presented here, there could be an early regression in the SCO of the communicating cases that is not present in the non-communicating case

AQP4, Astrogenesis, and Hydrocephalus: A New Neurological Perspective

Aquaporin 4 (AQP4) is a cerebral glial marker that labels ependymal cells and astrocytes’ endfeet and is the main water channel responsible for the parenchymal fluid balance. However, in brain development, AQP4 is a marker of glial stem cells and plays a crucial role in the pathophysiology of pediatric hydrocephalus. Gliogenesis characterization has been hampered by a lack of biomarkers for precursor and intermediate stages and a deeper understanding of hydrocephalus etiology is needed. This manuscript is a focused review of the current research landscape on AQP4 as a possible biomarker for gliogenesis and its influence in pediatric hydrocephalus, emphasizing reactive astrogliosis. The goal is to understand brain development under hydrocephalic and normal physiologic conditions

NTS, NTSR1 and ERs in the Pituitary–Gonadal Axis of Cycling and Postnatal Female Rats after BPA Treatment

The neuropeptide neurotensin (NTS) is involved in regulating the reproductive axis and is expressed at each level of this axis (hypothalamus–pituitary–gonads). This dependence on estrogen levels has been widely demonstrated in the hypothalamus and pituitary. We focused on confirming the relationship of NTS with estrogens and the gonadal axis, using a particularly important environmental estrogenic molecule, bisphenol-A (BPA). Based on the experimental models or in vitro cell studies, it has been shown that BPA can negatively affect reproductive function. We studied for the first time the action of an exogenous estrogenic substance on the expression of NTS and estrogen receptors in the pituitary-gonadal axis during prolonged in vivo exposure. The exposure to BPA at 0.5 and 2 mg/kg body weight per day during gestation and lactation was monitored through indirect immunohistochemical procedures applied to the pituitary and ovary sections. Our results demonstrate that BPA induces alterations in the reproductive axis of the offspring, mainly after the first postnatal week. The rat pups exposed to BPA exhibited accelerated sexual maturation to puberty. There was no effect on the number of rats born per litter, although the fewer primordial follicles suggest a shorter fertile life