Optimization Criteria and Efficiency of a Thermoelectric Generator.

The efficiency of a thermoelectric generator model under maximum conditions is presented for two optimization criteria proposed under the context of finite-time thermodynamics, namely, the efficient power criterion and the Omega function, where this last function represents a trade-off between useful and lost energy. The results are compared with the performance of the device at maximum power output. A macroscopic thermoelectric generator (TEG) model with three possible sources of irreversibilities is considered: (i) the electric resistance R for the Joule heating, (ii) the thermal conductances Kh and Kc of the heat exchangers between the thermal baths and the TEG, and (iii) the internal thermal conductance K for heat leakage. In particular, two configurations of the macroscopic TEG are studied: the so-called exoreversible case and the endoreversible limit. It shows that for both TEG configurations, the efficiency at maximum Omega function is always greater than that obtained in conditions of maximum efficient power, and this in turn is greater than that of the maximum power regime.

Resultados de Femto-LASIK obtenidos por un fellow durante un programa de formación en cirugía refractiva / Femto-LASIK outcomes obtained by a fellowship trainee during a refractive surgery training program

Objetivo Informar por primera vez sobre los resultados clínicos y la satisfacción de los pacientes operados de cirugía refractiva con láser por un fellow durante un programa de formación en cirugía corneal y refractiva en Latinoamérica. Métodos En este estudio prospectivo e intervencionista se revisaron las historias clínicas de los primeros 100 casos consecutivos de cirugía refractiva realizados por un solo fellow del departamento de córnea de la Asociación para Evitar la Ceguera en México entre marzo de 2018 y junio de 2018. La técnica LASIK asistida por femtosegundo se realizó en todos los ojos. Los resultados visuales y refractivos se evaluaron durante el primer año de seguimiento. La satisfacción del paciente se midió 6 meses después de la cirugía con 5 preguntas creadas por el autor. Resultados Se evaluaron datos de 100 ojos de 50 pacientes consecutivos. Después de 12 meses de la cirugía, la agudeza visual no corregida (AVNC) fue de 0,01logMAR. El equivalente esférico pasó de –3,91±2,28D preoperatoriamente a –0,22±0,28D. No se perdieron líneas en la agudeza visual mejor corregida (AVMC). La refracción manifiesta se mantuvo estable durante el primer año después de la cirugía. Las 5 preguntas creadas por el autor revelaron un alto grado de confianza y satisfacción del paciente. Conclusiones Los resultados refractivos y visuales obtenidos mediante Femto-LASIK por un fellow de cirugía corneal y refractiva fueron buenos. Del mismo modo se demostró una alta satisfacción y confianza del paciente en el cirujano en periodo de aprendizaje en un centro formativo de cirugía refractiva en Latinoamérica (AU)

Purpose To report, for the first time, the clinical outcomes and patient satisfaction of laser refractive surgery performed by a trainee during a corneal and refractive surgery fellowship program in Latin America. Methods This prospective and interventionist study reviewed the clinical charts of the first 100 consecutive refractive surgery cases performed by a single Cornea Fellowship trainee between March 2018 and June 2018 in the Blindness Prevention Association of Mexico (Asociación para Evitar la Ceguera en Mexico). Femtosecond LASIK was performed in all eyes. Visual and refractive outcomes were evaluated during the first year of follow-up. Patient satisfaction was measured using 5 author-created questions 6 months after surgery. Results Data of 100 eyes of 50 consecutive patients were evaluated. One year after the surgery, mean uncorrected distance visual acuity (UDVA) was 0.01logMAR. Spherical equivalent error passed from –3.91±2.28D preoperatively to –0.22±0.28D. No eyes lost lines in corrected distance visual acuity (CDVA). Manifest refraction maintained stable during the first year after surgery. The five author-created questions revealed a high level of confidence and patient satisfaction. Conclusions Femto-LASIK performed by a corneal and refractive surgery fellowship trainee showed good refractive and visual outcomes, as well as high patient satisfaction and confidence in a refractive surgery centre in Latin America (AU)

Femto-LASIK outcomes obtained by a fellowship trainee during a refractive surgery training program.

PURPOSE: To report, for the first time, the clinical outcomes and patient satisfaction of laser refractive surgery performed by a trainee during a corneal and refractive surgery fellowship program in Latin America. METHODS: This prospective and interventionist study reviewed the clinical charts of the first 100 consecutive refractive surgery cases performed by a single Cornea Fellowship trainee between March 2018 and June 2018 in the Blindness Prevention Association of Mexico (Asociación para Evitar la Ceguera en Mexico). Femtosecond LASIK was performed in all eyes. Visual and refractive outcomes were evaluated during the first year of follow-up. Patient satisfaction was measured using 5 author-created questions 6 months after surgery. RESULTS: Data of 100 eyes of 50 consecutive patients were evaluated. One year after the surgery, mean uncorrected distance visual acuity (UDVA) was 0.01 logMAR. Spherical equivalent error passed from -3.91 ± 2.28 D preoperatively to -0.22 ± 0.28 D. No eyes lost lines in corrected distance visual acuity (CDVA). Manifest refraction maintained stable during the first year after surgery. The five author-created questions revealed a high level of confidence and patient satisfaction. CONCLUSIONS: Femto-LASIK performed by a corneal and refractive surgery fellowship trainee showed good refractive and visual outcomes, as well as high patient satisfaction and confidence in a refractive surgery centre in Latin America.

Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure.

Symptoms of depressive disorders such as anhedonia and despair can be a product of an aberrant adaptation to stress conditions. Chronic unpredictable stress model (CUS) can generate an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) and induce a reduction of neurotrophin signaling and the proliferation of neural progenitors in the adult dentate gyrus, together with increased oxidative stress. Levels of the endocannabinoid anandamide (AEA) seem to affect these depression-by-stress-related features and could be modulated by fatty acid amide hydrolase (FAAH). We aimed to evaluate the effects of FAAH inhibitor, URB597, on depressive-like behavior and neural proliferation of mice subjected to a model of CUS. URB597 was administered intraperitoneally at a dose of 0.2 mg/kg for 14 days after CUS. Depressive-like behaviors, anhedonia, and despair were evaluated in the splash and forced swimming tests, respectively. Alterations at the HPA axis level were analyzed using the relative weight of adrenal glands and serum corticosterone levels. Oxidative stress and brain-derived neurotrophic factor (BDNF) were also evaluated. Fluorescence immunohistochemistry tests were performed for the immunoreactivity of BrdU and Sox2 colabeling for comparison of neural precursors. The administration of URB597 was able to reverse the depressive-like behavior generated in mice after the model. Likewise, other physiological responses associated with CUS were reduced in the treated group, among them, increase in the relative weight of the adrenal glands, increased oxidative stress, and decreased BDNF and number of neural precursors. Most of these auspicious responses to enzyme inhibitor administration were blocked by employing a cannabinoid receptor antagonist. In conclusion, the chronic inhibition of FAAH generated an antidepressant effect, promoting neural progenitor proliferation and BDNF expression, while reducing adrenal gland weight and oxidative stress in mice under the CUS model.

ß-Caryophyllene exerts protective antioxidant effects through the activation of NQO1 in the MPTP model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder, caused by the selective death of dopaminergic neurons in the substantia nigra pars compacta. ß-caryophyllene (BCP) is a phytocannabinoid with several pharmacological properties, producing anti-inflammatory and antihypertensive effects. In addition, BCP protects dopaminergic neurons from neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), yet it remains unclear if this effect is due to its antioxidant activity. To assess whether this is the case, the effect of BCP on the expression and activity of NAD(P)H quinone oxidoreductase (NQO1) was evaluated in mice after the administration of MPTP. Male C57BL/6 J mice were divided into four groups, the first of which received saline solution i.p. in equivalent volume and served as a control group. The second group received MPTP. The second group received MPTP hydrochloride (5 mg/kg, i.p.) daily for seven consecutive days. The third group received BCP (10 mg/kg) for seven days, administered orally and finally, the fourth group received MPTP as described above and BCP for 7 days from the fourth day of MPTP administration. The results showed that BCP inhibits oxidative stress-induced cell death of dopaminergic neurons exposed to MPTP at the same time as it enhances the expression and enzymatic activity of NQO1. Also, the BCP treatment ameliorated motor dysfunction and protected the dopaminergic cells of the SNpc from damage induced by MPTP. Hence, BCP appears to achieve at least some of its antioxidant effects by augmenting NQO1 activity, which protects cells from MPTP toxicity. Accordingly, this phytocannabinoid may represent a promising pharmacological option to safeguard dopaminergic neurons and prevent the progression of PD.

Tendencia de la mortalidad por fibrosis quística en Chile, 1997-2017 / Cystic fibrosis mortality trend in chile, 1997-2017

Introducción. La Fibrosis Quística es la enfermedad hereditaria con pronóstico reducido más frecuente en raza blanca. Su incidencia varía según etnias. En Chile, la incidencia estimada es de 1/10.000 habitantes y la evidencia nacional acerca de la magnitud y caracterización de defunciones es escasa. El objetivo de este estudio es determinar la evolución de mortalidad por fibrosis quística en Chile durante 1997-2017. Materiales y Métodos. Estudio descriptivo retrospectivo sobre la tendencia de mortalidad por fibrosis quística en Chile. A partir de bases de datos secundarias del sistema de estadísticas de mortalidad del país, se analizó la cohorte de fallecidos registrado en el certificado de defunción como fibrosis quística. Se calcularon tasas de mortalidad crudas y ajustadas para todos los años observados. Se realizó un análisis para las defunciones en menores 40 años; según las variables sexo, edad y región. Se estimó el cambio porcentual anual utilizando el programa Joinpoint-Regression. Resultados. Se registraron 198 defunciones (49% mujeres). La edad media y mediana de defunción aumentaron progresivamente, desde 1997-2001 con media 8,5 y mediana 6 años a 2013-2017 con media 19,6 y mediana 20 años (p-valor<0,05). La tasa de mortalidad en los menores de 1 año presentó una tendencia decreciente con un cambio porcentual anual de - 32,5%, estadísticamente significativo. La región de Atacama presentó un riesgo de muerte 6,12 veces mayor que el promedio del país. Discusión. En Chile, la edad de defunción por fibrosis quística ha aumentado progresivamente y la mortalidad en los <1 año ha disminuido a lo largo de los últimos años.

Introduction. Cystic Fibrosis is the most frequent hereditary disease in whites, with a reduced prognosis. Its incidence varies by ethnicity. In Chile, the estimated incidence is 1/10,000 inha-bitants and national evidence regarding the magnitude and characterization of deaths is scarce.The aim of this study es to describe the evolution of cystic fibrosis mortality in Chile during 1997-2017. Materials and Methods. Retrospective descriptive study on the mortality trend due to cystic fibrosis in Chile. From secondary databases of the country's mortality statistics system, the cohort of deceased due to cystic fibrosis, as registered in the death certificate was analyzed. Crude and adjusted mortality rates were calculated for all observed years. An analysis was performed for deaths in persons younger 40 years; according to the variables of sex, age and region. The annual percentage change was estimated using the Joinpoint-Regression program.Results. 198 deaths were registered (49% women). For those younger than 40 years at the time of death, the mean and median age of death increased progressively, from mean 8.5 and median 6 years in 1997 to 2001 to a mean of 19.6 and median of 20 years in 2013-2017 (p-value <0.05). The mortality rate in under 1 year of ages presented a decreasing trend with an annual percentage change of -32.5%. The Atacama region presented a risk of death 6.12 times higher than the country's average.Discussion. In Chile, the age of death due to cystic fibrosis has progressively increased and mortality in <1 year has decreased in recent years

Queratoplastia lamelar anterior en el manejo de un tumor dermoide central en un bebé / Anterior lamellar keratoplasty for the management of a central dermoid tumour in a baby

Bebé de 3 meses de edad al que traen por presencia desde el nacimiento de una lesión blanquecina sobre la córnea del ojo derecho. Debido a las características clínicas y ultrasónicas de la lesión, se realizó una queratoplastia lamelar anterior manual. La anatomía patológica demostró la presencia de un coristoma epibulbar simple de grado II. Los tumores dermoides suelen ser considerados benignos, pero pueden afectar de manera muy grave a la visión de un paciente pediátrico en función de su localización. La posibilidad de ambliopía en este tipo de casos obliga a procedimientos quirúrgicos con relativa urgencia. En los casos de afectación del eje visual sin implicaciones intraoculares la técnica de elección es la queratoplastia lamelar anterior

A 3-month-old baby presented with a whitish lesion over the right cornea since birth. Due to the clinical and ultrasonic characteristics of the lesion, a manual anterior lamellar keratoplasty was performed. Histopathological examination showed it to be a simple grade II epibulbar choristoma. Although dermoid tumours are usually considered as benign, some of them, depending on their location, can seriously affect the vision of a paediatric patient. Due to the high probability of amblyopia in these cases, a surgical procedure is mandatory. Anterior lamellar keratoplasty is recommended when the visual axis is compromised without intraocular implications

Anterior lamellar keratoplasty for the management of a central dermoid tumour in a baby. / Queratoplastia lamelar anterior en el manejo de un tumor dermoide central en un bebé.

A 3-month-old baby presented with a whitish lesion over the right cornea since birth. Due to the clinical and ultrasonic characteristics of the lesion, a manual anterior lamellar keratoplasty was performed. Histopathological examination showed it to be a simple grade II epibulbar choristoma. Although dermoid tumours are usually considered as benign, some of them, depending on their location, can seriously affect the vision of a paediatric patient. Due to the high probability of amblyopia in these cases, a surgical procedure is mandatory. Anterior lamellar keratoplasty is recommended when the visual axis is compromised without intraocular implications.

Estructura y función de las subunidades del receptor a glutamato tipo NMDA / Structure and function of NMDA-type glutamate receptor subunits

Introducción: Realizar una revisión de la fisiología de las subunidades del receptor a glutamato tipo N-metil-D-aspartato (NMDA). Desarrollo: El acido glutámico (Glu) es el principal neurotransmisor excitador del sistema nervioso central la cual interactúa con dos tipos de receptores clasificados como: metabotrópicos y ionotrópicos. Los receptores ionotrópicos se dividen de acuerdo a la afinidad de sus agonistas específicos en: N-metil-D-aspartato (NMDA), ácido α-amino-3-hidroxi-5-metil-4-isoxazol (AMPA) y acido kaínico (KA). Los receptores NMDA son estructuras macromoleculares que se forman por combinaciones de diferentes subunidades: NMDAR1 (NR1), NMDAR2 (NR2) y (NR3). Conclusiones:El estudio de este receptor ha sido de gran interés por la función que desempeña en la plasticidad sináptica, pero sobre todo por la permeabilidad que tiene para el ion Ca++. En esta revisión se analiza la composición molecular del receptor NMDA, así como las distintas variantes de edición de la subunidad NR1 que en asociación con la subunidad NR2 forman el principal dímero de este receptor. La composición, estructura y funcionalidad y sus distintos patrones de expresión tanto temporal y espacial, ha permitido conocer la versatilidad y la diversidad funcional tanto de las diferentes isoformas de la subunidad NR1, así como las distintas propiedades farmacológicas de la subunidad NR2 (AU)

Introducion: To review the physiology of the glutamate receptor subunits such as N-methyl-D-aspartate (NMDA). Development:Glutamic acid (Glu) is the major excitatory neurotransmitter in the central nervous system which interacts with two types classified into two types: metabotropic and ionotropic. Ionotropic receptors are classified according to the affinity of their specific agonists: N-methyl-D-aspartate (NMDA), α-amino acid-3-hydroxy-5-methyl-4-isoxazole (AMPA) and kainic acid (KA). NMDA receptors are macromolecular structures that are formed by different combinations of subunits, NMDAR1 (NR1), NMDAR2 (NR2) and NMDAR3 (NR3). Conclusions: The study of this receptor has been of great interest due to its role in synaptic plasticity, but mainly due to the permeability it has to Ca++ ion. This review examines the molecular composition of NMDA receptor and the variants of NR1 subunit edition in association with NR2 subunit dimer, the main form of this receptor. The composition, structure and function and their distinct expression patterns in both time and space, has shown the versatility and diversity of functionally different isoforms of the NR1 subunit and various pharmacological properties of the NR2 subunit (AU)

[Structure and function of NMDA-type glutamate receptor subunits]. / Estructura y función de las subunidades del receptor a glutamato tipo NMDA.

INTRODUCTION: To review the physiology of the glutamate receptor subunits such as N-methyl-D-aspartate (NMDA). DEVELOPMENT: Glutamic acid (Glu) is the major excitatory neurotransmitter in the central nervous system which interacts with two types classified into two types: metabotropic and ionotropic. Ionotropic receptors are classified according to the affinity of their specific agonists: N-methyl-D-aspartate (NMDA), α-amino acid-3-hydroxy-5-methyl-4-isoxazole (AMPA) and kainic acid (KA). NMDA receptors are macromolecular structures that are formed by different combinations of subunits, NMDAR1 (NR1), NMDAR2 (NR2) and NMDAR3 (NR3) CONCLUSIONS: The study of this receptor has been of great interest due to its role in synaptic plasticity, but mainly due to the permeability it has to Ca(++) ion. This review examines the molecular composition of NMDA receptor and the variants of NR1 subunit edition in association with NR2 subunit dimer, the main form of this receptor. The composition, structure and function and their distinct expression patterns in both time and space, has shown the versatility and diversity of functionally different isoforms of the NR1 subunit and various pharmacological properties of the NR2 subunit.

HIF-1α expression in the hippocampus and peripheral macrophages after glutamate-induced excitotoxicity.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a master transcription factor that regulates the response to hypoxia and ischemia and induces the expression of various genes, including vascular endothelial growth factor (VEGF) and erythropoietin (EPO). This study shows the systemic response of increased HIF-1α, EPO, and VEGF mRNA and protein. In addition, VEGF expression was increased in neurons and over-expressed in glial cells in a model of neuroexcitotoxicity in the hippocampus, in which rats were neonatally exposed to high glutamate concentrations. Simultaneous increases in HIF-1α, EPO and VEGF mRNA in peritoneal macrophages were also observed. Our study is consistent with the hypothesis that these genes exert a protective effect in response to neurotoxicity.

Protective effects of tryptophan on neuro-inflammation in rats after administering lipopolysaccharide.

Tryptophan (TRP), which plays an important role in immune system regulation, protein synthesis, serotonin (5-HT) and melatonin production, is a potent endogenous free radical scavenger and antioxidant. The aim of this work was to determine the efficacy of TRP in neuro-inflammation induced by systemic administration of lipopolysacharide (LPS, 20mg/kg) which promotes the synthesis of free radical (LPO: MDA and 4-HDA), and pro-inflammatory cytokine Interferon-γ (IFN-γ) in different brain regions (cerebral cortex and hippocampus) of rats. Experiments were performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein), cerebral cortex and hippocampus were evaluated for lipid peroxidation (LPO) products, nitrites, nitrates and plasmatic concentration of IFN-γ. LPO levels in LPS+TRP groups were significantly decreased than that obtained in the LPS group. However, there were no observed differences in plasmatic levels of nitrites and nitrates as well as IFN-γ, neither in the cerebral cortex or hippocampus. The TRP has protective effect in the oxidative damage in a model of endotoxic shock in the breading nurslings induced by the systemic administration of LPS, acting as a scavenger of free radicals. So, it can be proposed as an innocuous protector agent in the endotoxic shock process.

(-)-Epigallocatechin 3-gallate (EGCG) at the ocular surface inhibits corneal neovascularization.

Corneal neovascularization is often accompanied by inflammatory response and loss of their immune privilege which leads to significant visual impairment and worsens the prognosis of a subsequent penetrating keratoplasty. Several types of treatment are currently used. However, there are some associated limitations and complications. The consumption of (-)-epigallocatechin 3-gallate (EGCG) has been studied extensively as a potential treatment for a variety of carcinogenic and degenerative diseases due to its ability to suppress a variety of inflammatory and angiogenic factors such as NF-κB, IL-1ß, COX2, VEGF, and matrix metalloproteinases. These factors are involved in the development of corneal neovascularization. The safety of long-term EGCG administration as well as the drug's high solubility in water urge further investigation of the therapeutic potential of this drug. Therefore, we propose that the administration of EGCG to the ocular surface represents a new chemopreventive alternative to suppress the corneal neovascularization induced by inflammation.

Combinatorial gene therapy induces regression of hepatic encephalopathy.

Capillarization of the sinusoid impedes the clearance of neurotoxic substances in liver fibrosis. These events may result in hepatic encephalopathy. Neurological and hepatic features of rats after bile duct ligation (BDL) supplemented with Manganese (BDL+Mn(2+)) were examined. The 4-week-old BDL rats had elevated levels of ammonia and were concomitantly fed with 1 mg ml(-1) of MnCl(2) in drinking water (BDL/Mn(+2)). Five out of fifteen rats were killed and the serum, liver and brain tissue (striatum and substantia nigra) were recovered. Of the remaining BDL/Mn(+2)-cirrhotic animals (n=10), five were injected with a combination of Adenovirus-human plasminogen activator (Ad-huPA) and Adenovirus-matrix metalloproteinase-8 (Ad-MMP-8) (3 × 10(11)+1.5 × 10(11) vector particles per kg), and five with 4.5 × 10(11) vector particles per kg of Adenovirus-ß-galactosidase (Ad-ß-Gal). This treatment was carried on for 10 days. The BDL/Mn(+2) rats displayed tremor, rigidity and gait abnormalities, which improved notably with combinatorial gene therapy, as well as motor coordination. Liver fibrosis was evidently less after treatment with Ad-huPA+Ad-MMP-8 (25%). In the brain (striatum), Ad-huPA+Ad-MMP-8 treatment rendered higher concentrations of dopamine compared with Ad-ß-Gal-treated encephalopathic rats (210 and 162 ng g(-1) of tissue, respectively). The BDL/Mn(+2) animals and controls treated with Ad-ß-Gal showed abnormal morphology in astrocytes (gliosis) in striatum and substantia nigra, in which expressions of green fibrillar acidic protein and tyrosine hydroxylase were altered. These abnormalities decreased with Ad-huPA+Ad-MMP-8 treatment. Importantly, the latter animals showed an increment in sprouting of nervous fibers in substantia nigra. Combinatorial gene therapy improves neuroanatomical and neurochemical characteristics similar to human hepatic encephalopathy.

Expression of HIF-1 alpha, VEGF and EPO in peripheral blood from patients with two cardiac abnormalities associated with hypoxia.

OBJECTIVES: HIF-1 alpha (hypoxia-inducible factor-1 alpha) mediates the responses of mammalian cells to hypoxia/ischemia by inducing the expression of adaptive gene products (e.g., vascular endothelial growth factor (VEGF) and erythropoietin (EPO)). Persistent pulmonary hypertension of the newborn (PPHN) and cyanotic congenital heart disease (CCHD) are common neonatal diseases considered as paradigms of hypoxemia. Since the expression HIF-1 alpha, VEGF and EPO in newborns diagnosed with these diseases has yet to be studied, we set out to define the expression of these genes in peripheral blood from newborn infants diagnosed with PPHN and CCHD. DESIGN AND METHODS: The mRNA transcripts encoding HIF-1 alpha, VEGF and EPO were measured by RT-PCR in healthy newborn infants and infants diagnosed with PPHN and CCHD. RESULTS: An important increase in HIF-1 alpha expression was observed in both pathological conditions, accompanied by significant increases in VEGF and EPO expression when compared to healthy infants. CONCLUSIONS: HIF-1 alpha mRNA expression increases in newborn infants with PPHN or CCHD, as does the expression of its target genes VEGF and EPO.

Changes in hippocampal NMDA-R subunit composition induced by exposure of neonatal rats to L-glutamate.

Overactivation of NMDA-Rs may mediate excitotoxic cell death associated with epileptic seizures, and hypoxic-ischemic conditions. We assessed whether repeated subcutaneous administration of l-glutamate to neonatal rats affects the subunit composition of NMDA-Rs. Accordingly, cortical and hippocampal tissue from 14-day-old rats was analyzed by Western blotting and RT-PCR to quantify the protein and mRNA expression of different NMDA-R subunits. In addition, tissue sections were Nissl stained to assess the cell damage in this tissue. Early exposure of neonatal rats to L-glutamate differentially affects the expression of mRNA transcripts for NMDA-R subunits in the cerebral cortex and hippocampus. In the cerebral cortex, a decrease in NR2B subunit mRNA expression was observed, as well as a loss of NR1 and NR2A protein. By contrast, neonatal L-glutamate administration augmented the transcripts encoding the NR1, NR2B, and NR2C subunits in the hippocampal formation. The expression of mRNA encoding the NR2A subunit was not affected by neonatal L-glutamate administration in either of the brain regions examined. This differential expression of NMDA-R subunits following neonatal exposure to L-glutamate may represent an adaptive response of the glutamate receptors to overactivation in order to reduce the effect of high L-glutamate during the early period of life when the animal is more vulnerable to excitotoxicity.

Role of p38 MAPK and pro-inflammatory cytokines expression in glutamate-induced neuronal death of neonatal rats.

Pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6 rises significantly during neuronal damage and activate the signaling p38 MAPK pathway, which is involved in the apoptotic (AP) neuronal death. Systemic administration of glutamate as monosodium salt (MSG) to newborn animals induces neuronal death, however whether neurons die by AP or necrosis through MAPK p38 pathway activation it is unknown. In this study, TNF-alpha, IL-1beta and IL-6 expression levels, AP neuronal death and cellular type that produces TNF-alpha was also identified in the cerebral cortex (CC) and striatum (St) of rats at 8, 10, and 14 days of age after neonatal exposure to MSG. TNF-alpha production and AP neuronal death was significantly increased in the CC at PD8-10, and in the St in all ages studied by excitotoxicity effect induced with MSG. This effect was completely inhibited by SB203580 (p38 inhibitor) in both regions studied. TNF-alpha, IL-1beta and IL-6 RNAm increased after MSG administration, whereas SB203580 did not modify their expression. These data indicates that neuronal death induced by excitotoxicity appears to be mediated through p38 signaling pathway activated by TNF-alpha and their inhibition may have an important neuroprotective role as part of anti-inflammatory therapeutic strategy.