URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia-Ischemia and Enhances Neurogenesis in Females.

The need for new and effective treatments for neonates suffering from hypoxia-ischemia is urgent, as the only implemented therapy in clinics is therapeutic hypothermia, only effective in 50% of cases. Cannabinoids may modulate neuronal development and brain plasticity, but further investigation is needed to better describe their implication as a neurorestorative therapy after neonatal HI. The cannabinoid URB447, a CB1 antagonist/CB2 agonist, has previously been shown to reduce brain injury after HI, but it is not clear whether sex may affect its neuroprotective and/or neurorestorative effect. Here, URB447 strongly reduced brain infarct, improved neuropathological score, and augmented proliferative capacity and neurogenic response in the damaged hemisphere. When analyzing these effects by sex, URB447 ameliorated brain damage in both males and females, and enhanced cell proliferation and the number of neuroblasts only in females, thus suggesting a neuroprotective effect in males and a double neuroprotective/neurorestorative effect in females.

Relación entre la compresión maxilar y potencial impactación del canino superior: Scoping review

El canino maxilar permanente corresponde al segundo diente más frecuentemente impactado en el arco dental. La etiología de esta patología aún no está totalmente definida, sin embargo, investigadores plantean la deficiencia del ancho del hueso maxilar como una posible causa. Objetivo: Investigar la evidencia que asocia menores dimensiones transversales del maxilar a la ocurrencia de la impactación de caninos superiores y esclarecer la posible relación. Materiales y métodos: Se realizó una revisión sistemática exploratoria a partir de una búsqueda amplia de la literatura en bases de datos PubMed, Cochrane, EBSCO y Multibuscador UNAB. Los artículos fueron recopilados, identificados y filtrados según el diagrama de flujo de declaración PRISMA. Resultados: La búsqueda identificó 755 estudios, de los cuales 14 fueron incluidos. Los estudios varían en diseño, edad de estudio y métodos de diagnóstico. La mitad de los estudios reporta una asociación positiva entre compresión maxilar e impactación canina superior, mientras que la otra mitad una asociación negativa. Conclusiones: No hay evidencia suficiente para poder asociar compresión maxilar con impactación de caninos superiores. Estudios con métodos de diagnóstico rigurosos son necesarios para una mejor comprensión. No obstante, se enfatiza la importancia de un diagnóstico precoz, para garantizar mejores resultados y pronóstico más favorable.

The permanent maxillary canine is the second most frequently impacted tooth in the dental arch. The etiology of this disease is not completely defined, yet some researchers propose the deficiency of the width from the maxilla as a possible cause. Objective: To investigate available evidence correlating smaller transverse maxilla dimensions with the occurrence of potential impaction of upper canines and clarify the possible relation. Materials and methods: A systematic exploratory review was carried out based on comprehensive search of the literature in databases such as PubMed, Cochrane, EBSCO and UNAB multi search engine. The articles were compiled, identified and filtered systematically according to the PRISMA flow diagram. Results: Our search identified 755 studies, 14 of which were included. These studies vary in design, patients age, and methods for detection. Half of the studies show a positive correlation between maxillary compression and potential upper canine impaction, whereas the other half show a negative correlation. Conclusions: There is not enough evidence to link maxillary compression to upper canine impaction. Studies with rigorous diagnostic methods for detection are necessary for a better understanding of this relation. Nonetheless, the importance of early diagnosis must be emphasized to guarantee better results and a more favorable prognosis.

Effects of Cannabidiol, Hypothermia, and Their Combination in Newborn Rats with Hypoxic-Ischemic Encephalopathy.

Therapeutic hypothermia is well established as a standard treatment for infants with hypoxic-ischemic (HI) encephalopathy but it is only partially effective. The potential for combination treatments to augment hypothermic neuroprotection has major relevance. Our aim was to assess the effects of treating newborn rats following HI injury with cannabidiol (CBD) at 0.1 or 1 mg/kg, i.p., in normothermic (37.5°C) and hypothermic (32.0°C) conditions, from 7 d of age (neonatal phase) to 37 d of age (juvenile phase). Placebo or CBD was administered at 0.5, 24, and 48 h after HI injury. Two sensorimotor (rotarod and cylinder rearing) and two cognitive (novel object recognition and T-maze) tests were conducted 30 d after HI. The extent of brain damage was determined by magnetic resonance imaging, histologic evaluation, magnetic resonance spectroscopy, amplitude-integrated electroencephalography, and Western blotting. At 37 d, the HI insult produced impairments in all neurobehavioral scores (cognitive and sensorimotor tests), brain activity (electroencephalography), neuropathological score (temporoparietal cortexes and CA1 layer of hippocampus), lesion volume, magnetic resonance biomarkers of brain injury (metabolic dysfunction, excitotoxicity, neural damage, and mitochondrial impairment), oxidative stress, and inflammation (TNFα). We observed that CBD or hypothermia (to a lesser extent than CBD) alone improved cognitive and motor functions, as well as brain activity. When used together, CBD and hypothermia ameliorated brain excitotoxicity, oxidative stress, and inflammation, reduced brain infarct volume, lessened the extent of histologic damage, and demonstrated additivity in some parameters. Thus, coadministration of CBD and hypothermia could complement each other in their specific mechanisms to provide neuroprotection.

New Insights into the Application of High-Pressure Processing and Storage Time and Temperature to Sliced Iberian Chorizo.

Producing dry-cured meats with relatively high aw and pH allows companies to cut costs to the detriment of microbial control. The purpose of this study was to evaluate for the first time the effect of High Processing Pressure (HPP) and storage temperature on the microbial counts, instrumental color, oxidation and sensory characteristics of sliced Iberian chorizo with high aw and pH. First, 600 MPa was applied for 480 s to sliced chorizo with aw: 0.88 and pH: 6.01, and the treated and untreated samples were stored at 4 or 20 °C for 90 or 180 days. HPP, storage time and storage at 20 °C were successful at decreasing the microbial counts that were initially high. HPP and the storage temperature had a limited detrimental effect, whereas the storage time had a marked adverse effect on oxidation and some sensory traits. Despite the high aw and pH, no safety issues arose initially or during the storage at 4 or 20 °C. In conclusion, for chorizo with high aw and pH favoring high microbial counts, HPP may be an effective hurdle without a noticeable detrimental effect, and the economically convenient storage at 20 °C might be beneficial despite causing moderate quality loss.

Fallo multiorgánico neonatal tras asfixia perinatal / Neonatal multiple organ failure after perinatal asphyxia

La asfixia perinatal es un acontecimiento con efectos de gran alcance, pudiendo conducir no solo al desarrollo de encefalopatía neonatal, sino también a un fallo multiorgánico (FMO). Esta afectación posiblemente se deba a la redistribución del flujo sanguíneo, mediante el cual se conserva la irrigación de órganos vitales como el corazón, el cerebro y las glándulas suprarrenales, a expensas de su disminución en otros órganos.El objetivo del presente trabajo fue conocer la incidencia y la etiopatogenia de los órganos más frecuentemente afectados en el FMO neonatal tras la asfixia perinatal.Se realizó una búsqueda bibliográfica sistemática en las bases de datos Pubmed, Scopus y The Cochrane Library empleando los términos MeSH (ischemia AND hypoxia AND multiorgan dysfunction AND neonat*), (asphyxia AND multiorgan dysfunction AND neonat*) y (liver / kidney / digestive OR gastrointestinal / heart injury AND ischemia AND hypoxia AND neonat*). Se incluyeron trabajos clínicos y preclínicos posteriores al año 2000 y se excluyeron series de casos, cartas al director, cohortes sin grupo comparador y abstracts.En el presente trabajo describimos que el fallo multiorgánico asociado a la asfixia perinatal es un fenómeno frecuente y relevante en la morbimortalidad del neonato, pudiendo llegar a producir no solo alteraciones en riñón, hígado y tracto gastrointestinal, sino también miocardiopatía si el fenómeno se prolonga o es de elevada gravedad. (AU)

Perinatal asphyxia is an event with far-reaching consequences that can lead not only to the development of neonatal encephalopathy, but also to multiple organ failure (MOF). This ailment may result from the redistribution of blood flow, which would preserve the perfusion of vital organs such as the heart, brain and adrenal glands at the expense of other organs.The objective of the study was to determine the incidence and aetiopathogenesis of failure in the organs most frequently involved in neonatal MOF following perinatal asphyxia.We conducted a systematic literature search in the PubMed, Scopus and Cochrane Library databases using the MeSH terms (ischemia AND hypoxia AND multiorgan dysfunction AND neonat*), (asphyxia AND multiorgan dysfunction AND neonat*) and (liver/kidney/digestive OR gastrointestinal/heart injury AND ischemia AND hypoxia AND neonat*). We selected clinical and preclinical studies published after 2000 and excluded case series, letters to the editor, cohort studies without comparison groups and abstracts.In this study, we found that MOF associated with perinatal asphyxia is a frequent phenomenon with a relevant impact on neonatal morbidity and mortality, as it can cause changes not only in the kidney, liver and gastrointestinal tract, but also cardiomyopathy if the ailment is protracted or severe. (AU)

Neonatal multiple organ failure after perinatal asphyxia.

Perinatal asphyxia is an event with far-reaching consequences that can lead not only to the development of neonatal encephalopathy, but also to multiple organ failure (MOF). This ailment may result from the redistribution of blood flow, which would preserve the perfusion of vital organs such as the heart, brain and adrenal glands at the expense of other organs. The objective of the study was to determine the incidence and aetiopathogenesis of failure in the organs most frequently involved in neonatal MOF following perinatal asphyxia. We conducted a systematic literature search in the PubMed, Scopus and Cochrane Library databases using the MeSH terms (ischemia AND hypoxia AND multiorgan dysfunction AND neonat*), (asphyxia AND multiorgan dysfunction AND neonat*) and (liver/kidney/digestive OR gastrointestinal/heart injury AND ischemia AND hypoxia AND neonat*). We selected clinical and preclinical studies published after 2000 and excluded case series, letters to the editor, cohort studies without comparison groups and abstracts. In this study, we found that MOF associated with perinatal asphyxia is a frequent phenomenon with a relevant impact on neonatal morbidity and mortality, as it can cause changes not only in the kidney, liver and gastrointestinal tract, but also cardiomyopathy if the ailment is protracted or severe.

The Endocannabinoid System as a Target for Neuroprotection/Neuroregeneration in Perinatal Hypoxic-Ischemic Brain Injury.

The endocannabinoid (EC) system is a complex cell-signaling system that participates in a vast number of biological processes since the prenatal period, including the development of the nervous system, brain plasticity, and circuit repair. This neuromodulatory system is also involved in the response to endogenous and environmental insults, being of special relevance in the prevention and/or treatment of vascular disorders, such as stroke and neuroprotection after neonatal brain injury. Perinatal hypoxia-ischemia leading to neonatal encephalopathy is a devastating condition with no therapeutic approach apart from moderate hypothermia, which is effective only in some cases. This overview, therefore, gives a current description of the main components of the EC system (including cannabinoid receptors, ligands, and related enzymes), to later analyze the EC system as a target for neonatal neuroprotection with a special focus on its neurogenic potential after hypoxic-ischemic brain injury.

Asian in the Time of COVID-19: Creating a Social Work Agenda for Asian American and Pacific Islander Communities.

The health of Asian American and Pacific Islander (AAPI) communities remains an understudied area of racial/ethnic minority research in the United States, and even more so in the field of social work. The COVID-19 pandemic has highlighted how AAPI health and social welfare issues have not received adequate attention in social policy, social work practice, and research. Contrary to model minority myths, AAPIs are subject to racialized attitudes and discrimination, which have been associated with adverse physical and mental health outcomes, including increased anxiety, depression, and suicidality. Drawing from the theoretical framework of AsianCrit, which is grounded in critical race theory, authors analyze health disparities among AAPI communities as reflected in COVID-19 hospitalizations and fatalities, as well as increases in acts of anti-Asian racism and xenophobia. Better understanding health disparities of AAPI communities needs to be a key research issue for social workers in future years. The authors conclude by offering a short set of recommendations to improve social policy, social work practice, and research to more aptly address contemporary social issues impacting AAPI communities.

A Qualitative Evaluation of the Impacts of a Strength-based and Youth-driven Approach to Suicide Prevention in Rural and Minority Communities in Hawai'i.

Suicide is a serious public health issue, particularly for Native Hawaiians and Other Pacific Islander youth living in rural communities in Hawai'i. The Hawai'i's Caring Communities Initiative (HCCI) for Youth Suicide Prevention was implemented to address these concerns and used a strength-based, youthleadership approach to suicide prevention. A qualitative study was completed with youth leaders and adult community coordinators to evaluate the impacts of participating in HCCI. Participants included 9 adult community coordinators and 17 youth leaders ages 13-18 years. Coordinator interviews took place at a location of the interviewee's convenience, and youth leader focus groups were conducted at 1 of 6 rurally-based community organizations. A team of university staff members coded transcripts using a narrative approach and grouped codes into themes. Five themes emerged that fit with an adapted socio-ecological model framework, which included increased knowledge in suicide risk, pride in leadership identity, sense of positive relationships, positive affirmation from community members, and sustainability. Future efforts that focus on youth-related issues are encouraged to integrate a youth leadership model and preventive approach while considering implications such as long-term funding and capitalizing on community strengths and resources.

Cannabinoid-mediated Modulation of Oxidative Stress and Early Inflammatory Response after Hypoxia-Ischemia.

In the process of neonatal encephalopathy, oxidative stress and neuroinflammation have a prominent role after perinatal asphyxia. With the exception of therapeutic hypothermia, no therapeutic interventions are available in the clinical setting to target either the oxidative stress or inflammation, despite the high prevalence of neurological sequelae of this devastating condition. The endocannabinoid system (ECS), recently recognized as a widespread neuromodulatory system, plays an important role in the development of the central nervous system (CNS). This study aims to evaluate the potential effect of the cannabinoid (CB) agonist WIN 55,212-2 (WIN) on reactive oxygen species (ROS) and early inflammatory cytokine production after hypoxia-ischemia (HI) in fetal lambs. Hypoxic-ischemic animals were subjected to 60 min of HI by partial occlusion of the umbilical cord. A group of lambs received a single dose of 0.01 µg/kg WIN, whereas non-asphyctic animals served as controls. WIN reduced the widespread and notorious increase in inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1ß and IL-6 induced by HI, a modulatory effect not observed for oxidative stress. Our study suggests that treatment with a low dose of WIN can alter the profile of pro-inflammatory cytokines 3 h after HI.

Hope, help, and healing: Culturally embedded approaches to suicide prevention, intervention and postvention services with native Hawaiian youth.

Suicide rates have reached their highest documented levels in the United States with the greatest increases among indigenous youth, including Native Hawaiians. Culturally informed, effective prevention and treatment services are needed now more than ever for Native communities to heal and flourish. Multicomponent prevention and service strategies rooted in indigenous values and approaches show the most promise. Native Hawaiian communities are united around a common goal of suicide prevention, intervention and postvention, linking cultural meanings to improve understanding and guide local efforts. This paper highlights important cultural values to consider when developing and implementing suicide prevention, intervention and postvention. Strategies build upon the strengths of Native Hawaiian youth and their respective communities. Native Hawaiian sayings anchor each level and serve to organize a set of culturally informed and culturally embedded programs and approaches along the continuum of prevention, intervention and postvention. Application of indigenization to suicide prevention enhances connections to people and place, inspiring hope among Native Hawaiian youth, their families and their communities. (PsycINFO Database Record

Recent advances in cochlear hair cell regeneration-A promising opportunity for the treatment of age-related hearing loss.

The objective of this paper is to review current information regarding the treatment of age-related hearing loss by using cochlear hair cell regeneration. Recent advances in the regeneration of the inner ear, including the usefulness of stem cells, are also presented. Based on the current literature, cochlear cell regeneration may well be possible in the short term and cochlear gene therapy may also be useful for the treatment of hearing loss associated with ageing. The present review provide further insight into the pathogenesis of Inner Ear senescence and aged-related hearing loss and facilitate the development of therapeutic strategies to repair hair cells damaged by ageing. More research will be needed in order to translate them into an effective treatment for deafness linked to cochlear senescence in humans.

Role of Antioxidants in Neonatal Hypoxic-Ischemic Brain Injury: New Therapeutic Approaches.

Hypoxic-ischemic brain damage is an alarming health and economic problem in spite of the advances in neonatal care. It can cause mortality or detrimental neurological disorders such as cerebral palsy, motor impairment and cognitive deficits in neonates. When hypoxia-ischemia occurs, a multi-faceted cascade of events starts out, which can eventually cause cell death. Lower levels of oxygen due to reduced blood supply increase the production of reactive oxygen species, which leads to oxidative stress, a higher concentration of free cytosolic calcium and impaired mitochondrial function, triggering the activation of apoptotic pathways, DNA fragmentation and cell death. The high incidence of this type of lesion in newborns can be partly attributed to the fact that the developing brain is particularly vulnerable to oxidative stress. Since antioxidants can safely interact with free radicals and terminate that chain reaction before vital molecules are damaged, exogenous antioxidant therapy may have the potential to diminish cellular damage caused by hypoxia-ischemia. In this review, we focus on the neuroprotective effects of antioxidant treatments against perinatal hypoxic-ischemic brain injury, in the light of the most recent advances.

Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia.

Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult.

Antioxidant Treatments Recover the Alteration of Auditory-Evoked Potentials and Reduce Morphological Damage in the Inferior Colliculus after Perinatal Asphyxia in Rat.

Maturation of the auditory pathway is dependent on the central nervous system myelination and it can be affected by pathologies such as neonatal hypoxic ischemic (HI) encephalopathy. Our aim was to evaluate the functional integrity of the auditory pathway and to visualize, by histological and cellular methods, the damage to the brainstem using a neonatal rat model of HI brain injury. To carry out this morphofunctional evaluation, we studied the effects of the administration of the antioxidants nicotine, melatonin, resveratrol and docosahexaenoic acid after hypoxia-ischemia on the inferior colliculus and the auditory pathway. We found that the integrity of the auditory pathway in the brainstem was altered as a consequence of the HI insult. Thus, the auditory brainstem response (ABR) showed increased I-V and III-V wave latencies. At a histological level, HI altered the morphology of the inferior colliculus neurons, astrocytes and oligodendricytes, and at a molecular level, the mitochondria membrane potential and integrity was altered during the first hours after the HI and reactive oxygen species (ROS) activity is increased 12 h after the injury in the brainstem. Following antioxidant treatment, ABR interpeak latency intervals were restored and the body and brain weight was recovered as well as the morphology of the inferior colliculus that was similar to the control group. Our results support the hypothesis that antioxidant treatments have a protective effect on the functional changes of the auditory pathway and on the morphological damage which occurs after HI insult.

Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats.

Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

Effect of neonatal asphyxia on the impairment of the auditory pathway by recording auditory brainstem responses in newborn piglets: a new experimentation model to study the perinatal hypoxic-ischemic damage on the auditory system.

INTRODUCTION: Hypoxia-ischemia (HI) is a major perinatal problem that results in severe damage to the brain impairing the normal development of the auditory system. The purpose of the present study is to study the effect of perinatal asphyxia on the auditory pathway by recording auditory brain responses in a novel animal experimentation model in newborn piglets. METHOD: Hypoxia-ischemia was induced to 1.3 day-old piglets by clamping 30 minutes both carotid arteries by vascular occluders and lowering the fraction of inspired oxygen. We compared the Auditory Brain Responses (ABRs) of newborn piglets exposed to acute hypoxia/ischemia (n = 6) and a control group with no such exposure (n = 10). ABRs were recorded for both ears before the start of the experiment (baseline), after 30 minutes of HI injury, and every 30 minutes during 6 h after the HI injury. RESULTS: Auditory brain responses were altered during the hypoxic-ischemic insult but recovered 30-60 minutes later. Hypoxia/ischemia seemed to induce auditory functional damage by increasing I-V latencies and decreasing wave I, III and V amplitudes, although differences were not significant. CONCLUSION: The described experimental model of hypoxia-ischemia in newborn piglets may be useful for studying the effect of perinatal asphyxia on the impairment of the auditory pathway.

Afecciones neurológicas y barrera hematoencefálica. Limitaciones y estrategias para la liberación de fármacos al cerebro / Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain

Introducción. La incidencia de enfermedades del sistema nervioso central (SNC) aumenta a causa del envejecimiento de la sociedad. Desgraciadamente, los tratamientos clásicos para tratarlas no resultan efectivos debido a la presencia de la barrera hematoencefalica. Objetivo. Abordar las propiedades de la barrera hematoencefalica que impiden el transporte de los fármacos al cerebro y las principales estrategias para tratar las afecciones neurológicas. Desarrollo. La barrera hematoencefalica está compuesta principalmente por un endotelio vascular especializado y las células de la glia. Esta constituye una herramienta a disposición del organismo para aislar al SNC del resto del cuerpo. Sin embargo, también supone un impedimento para que muchos fármacos alcancen su diana en el cerebro. Conclusiones. Para poder tratar las afecciones neurológicas, los fármacos deben ser capaces de alcanzar el cerebro. Los agentes terapéuticos pueden diseñarse para que sean capaces de atravesar esta barrera, o bien facilitar su entra mediante el uso de sistemas de liberación. Para evaluar la efectividad de los tratamientos dirigidos a enfermedades del SNC, se emplean los modelos animales de enfermedades neurológicas así como modelos in vitro de barrera hematoencefalica (AU)

Introduction. The incidence in the central nervous system diseases has increased with a growing elderly population. Unfortunately, conventional treatments used to treat the mentioned diseases are frequently ineffective due to the presence of the blood brain barrier. Aim. To illustrate the blood-brain barrier properties that limit drug transport into the brain and the main strategies employed to treat neurologic disorders. Development. The blood-brain barrier is mainly composed of a specialized microvascular endothelium and of glial cells. It constitutes a valuable tool to separate the central nervous system from the rest of the body. Nevertheless, it also represents an obstacle to the delivery of therapeutic drugs to the brain. Conclusions. To be effective, drugs must reach their target in the brain. On one hand, therapeutic agents could be designed to be able to cross the blood brain barrier. On the other hand, drug delivery systems could be employed to facilitate the therapeutic agents’ entry into the central nervous system. In vivo models of neurological diseases, in addition to in vitro models of the blood brain barrier, have been widely employed for the evaluation of drugs utilized to treat central nervous system diseases (AU)

[Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain]. / Afecciones neurologicas y barrera hematoencefalica. Limitaciones y estrategias para la liberacion de farmacos al cerebro.

INTRODUCTION: The incidence in the central nervous system diseases has increased with a growing elderly population. Unfortunately, conventional treatments used to treat the mentioned diseases are frequently ineffective due to the presence of the blood brain barrier. AIM: To illustrate the blood-brain barrier properties that limit drug transport into the brain and the main strategies employed to treat neurologic disorders. DEVELOPMENT: The blood-brain barrier is mainly composed of a specialized microvascular endothelium and of glial cells. It constitutes a valuable tool to separate the central nervous system from the rest of the body. Nevertheless, it also represents an obstacle to the delivery of therapeutic drugs to the brain. CONCLUSIONS: To be effective, drugs must reach their target in the brain. On one hand, therapeutic agents could be designed to be able to cross the blood brain barrier. On the other hand, drug delivery systems could be employed to facilitate the therapeutic agents' entry into the central nervous system. In vivo models of neurological diseases, in addition to in vitro models of the blood brain barrier, have been widely employed for the evaluation of drugs utilized to treat central nervous system diseases.

TITLE: Afecciones neurologicas y barrera hematoencefalica. Limitaciones y estrategias para la liberacion de farmacos al cerebro.Introduccion. La incidencia de enfermedades del sistema nervioso central (SNC) aumenta a causa del envejecimiento de la sociedad. Desgraciadamente, los tratamientos clasicos para tratarlas no resultan efectivos debido a la presencia de la barrera hematoencefalica. Objetivo. Abordar las propiedades de la barrera hematoencefalica que impiden el transporte de los farmacos al cerebro y las principales estrategias para tratar las afecciones neurologicas. Desarrollo. La barrera hematoencefalica esta compuesta principalmente por un endotelio vascular especializado y las celulas de la glia. Esta constituye una herramienta a disposicion del organismo para aislar al SNC del resto del cuerpo. Sin embargo, tambien supone un impedimento para que muchos farmacos alcancen su diana en el cerebro. Conclusiones. Para poder tratar las afecciones neurologicas, los farmacos deben ser capaces de alcanzar el cerebro. Los agentes terapeuticos pueden diseñarse para que sean capaces de atravesar esta barrera, o bien facilitar su entrada mediante el uso de sistemas de liberacion. Para evaluar la efectividad de los tratamientos dirigidos a enfermedades del SNC, se emplean los modelos animales de enfermedades neurologicas asi como modelos in vitro de barrera hematoencefalica.

Neuroprotective effect of melatonin: a novel therapy against perinatal hypoxia-ischemia.

One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their lifetime. For this reason, new and more effective neuroprotective strategies are urgently required, in order to minimize as much as possible the neurological consequences of this encephalopathy. In this sense, interest has grown in the neuroprotective possibilities of melatonin, as this hormone may help to maintain cell survival through the modulation of a wide range of physiological functions. Although some of the mechanisms by which melatonin is neuroprotective after neonatal asphyxia remain a subject of investigation, this review tries to summarize some of the most recent advances related with its use as a therapeutic drug against perinatal hypoxic-ischemic brain injury, supporting the high interest in this indoleamine as a future feasible strategy for cerebral asphyctic events.