Age-related changes in medial septal cholinergic and GABAergic projection neurons and hippocampal neurotransmitter receptors: relationship with memory impairment.

The hippocampus, which provides cognitive functions, has been shown to become highly vulnerable during aging. One important modulator of the hippocampal neural network is the medial septum (MS). The present study attempts to determine how age-related mnemonic dysfunction is associated with neurochemical changes in the septohippocampal (SH) system, using behavioral and immunochemical experiments performed on young-adult, middle-aged and aged rats. According to these behavioral results, the aged and around 52.8% of middle-aged rats (within the "middle-aged-impaired" sub-group) showed both impaired spatial reference memory in the Morris water maze and habituation in the open field. Immunohistochemical studies revealed a significant decrease in the number of MS choline acetyltransferase immunoreactive cells in the aged and all middle-aged rats, in comparison to the young; however the number of gamma-aminobutyric acid-ergic (GABAergic) parvalbumin immunoreactive cells was higher in middle-aged-impaired and older rats compared to young and middle-aged-unimpaired rats. Western Blot analysis moreover showed a decrease in the level of expression of cholinergic, GABAergic and glutamatergic receptors in the hippocampus of middle-aged-impaired and aged rats in contrast to middle-aged-unimpaired and young rats. The present results demonstrate for the first time that a decrease in the expression level of hippocampal receptors in naturally aged rats with impaired cognitive abilities occurs in parallel with an increase in the number of GABAergic neurons in the MS, and it highlights the particular importance of inhibitory signaling in the SH network for memory function.

Modulation of prefrontal cortex function by basal forebrain cholinergic and GABAergic neurons at the behavioral and molecular level.

The present research aimed to study the effects of selective immunolesions of cholinergic or gamma-aminobutyric acid (GABA)ergic neurons in the nucleus basalis magnocellularis (NBM) on memory function as well as cholinergic activity and the level of expression of glutamatergic [NR2B subunit of N-methyl-D-aspartate(NMDA)] receptors in the medial prefrontal cortex (mPFC) and hippocampus of behaviorally characterized rats. In behavioral experiments, working memory was assessed by a spatial alternation testing procedure in a plus-maze, and acquisition and retention of spatial memory was evaluated in a Morris water maze. The rats were divided into three groups: the NBM cholinergic, GABAergic immunolesioned groups and the normal control group. Cholin acetyltransferase or parvalbumin staining of the NBM and acetylcholinesterase staining of the mPFC and hippocampal sections were performed to visualize the effects of immunotoxins. The electrophoresis and immunoblotting were run to evaluate the effect of NBM lesions on the amount of the NR2B subunit of NMDA receptors. The results indicate that the immunolesion of cholinergic NBM neurons impair spatial working memory, as well as long-term spatial memory which is accompanied by significant changes in glutamatergic (the NR2B subunit of NMDA receptor) and cholinergic markers in the mPFC, whereas immunolesion of GABAergic NBM neurons does not affect long-term spatial memory, it does though cause the impairment of working memory with a reduction of the NMDA NR2B receptor signaling in the mPFC. The present results demonstrate that the cholinergic and GABAergic NBM cell groups play diverse and complementary roles and are integrated in distinct NBM-mPFC networks that may play different roles in mPFC memory function.

Modulation of spatial memory and expression of hippocampal neurotransmitter receptors by selective lesion of medial septal cholinergic and GABAergic neurons.

The medial septum (MS) is an important modulator of hippocampal function. The degree of damage in which the particular set of septo-hippocampal projections contributes to the deficits of spatial memory with concomitant changes of hippocampal receptors expression has not been studied till present. Therefore, we investigated spatial memory and the expression level of cholinergic (α7 nACh and M1), GABAergic (α1 subunit of GABAA) and glutamatergic (NR2B subunit of NMDA and GluR 1 subunit of AMPA) receptors in the hippocampus following selective lesions of cholinergic and GABAergic septo-hippocampal projection. Learning process and long-term spatial memory were assessed using a Morris water maze. The obtained results revealed that in contrast to cholinergic lesions, rats with MS GABAergic lesions exhibit a retention deficit in 3 days after training. Western blot analyses revealed the MS cholinergic lesions have significant effect on the expression level of the M1 mACh receptors, while MS GABAergic lesions induce dramatic modulations of hippocampal glutamatergic, cholinergic and GABAergic receptors expression. These results for the first time demonstrated that selective lesions of MS cholinergic and GABAergic neurons differentially affect long-term spatial memory and the memory deficit after MS GABAergic lesion is paralleled with significant changes of hippocampal glutamate, GABA and acetylcholine receptors expression.

Memantine treatment prevents okadaic acid induced neurotoxicity at the systemic and molecular levels.

The present study was designed to investigate the effects of okadaic acid intracerebroventricular (ICV) injection on memory function and expression level of α7 subunit of nicotinic acetylcholine receptor (nAChR) and NR2B subunit of NMDA glutamate receptors in the hippocampus, as well as effect of the antidementic drug memantine on okadaic acid induced changes at systemic and molecular levels in rats. Okadaic acid was dissolved in artificial cerebrospinal fluid (aCSF) and injected ICV 200 ng/10 µl. Vehicle control received 10 µl of aCSF ICV bilaterally. Control and okadaic acid injected rats were divided into two subgroups: treated i.p. with saline or memantine (5 mg/kg daily for 13 days starting from the day of okadaic acid injection). Rats were trained in the dual-solution plus-maze task that can be solved by using place or response strategies. The Western immunoblotting was used to determine relative amount of hippocampal receptors protein levels. Obtained data revealed that okadaic acid ICV injected rats were severely impaired at acquiring the place version of the maze accompanied by significant decline in hippocampal α7 subunit of nACh receptors protein levels. Memantine treatment can prevent okadaic acid induced impairment of hippocampal-dependent spatial memory and accompanied by modulation of the expression level of α7 subunit of nACh and NR2B subunit of NMDA receptors in the hippocampus. Thus, our results support the presumption that α7 nACh receptors may play an important role in the cognitive enhancer effects of memantine and emphasize the role of cholinergic-glutamatergic interactions in memory.

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57 percent, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets.

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

A novel mutation (G114V) in the prion protein gene in a family with inherited prion disease.

Inherited prion diseases are characterized by mutations in the PRNP gene encoding the prion protein (PrP). We report a novel missense mutation in the PRNP gene (resulting in a G114V mutation in PrP) in members of a Uruguayan family with clinical and histopathologic features of prion disease. Affected individuals were characterized by an early age at onset, initial neuropsychiatric symptoms, late dementia with prominent pyramidal and extrapyramidal symptoms, and long disease duration.

Linfoma primario del sistema nervioso central en un paciente con sida / Primary central nervous system lymphoma in patient with AIDS

Se presenta una caso clínico de linfoma primario del sistema nervioso central (LPSNC) en una paciente con infección por virus de la inmunodeficiencia humana (VIH) en estadio sida. En este caso particular se destaca la confirmación por histopatología mediante intervención neuroquirúrgica de una lesión ocupante de espacio (LOE), lo que permitió instalar tratamiento oncoespecífico y terapia antirretroviral, lográndose buena evolución clínica. El obejtivo de la presente comunicación es realizar una revisión y actualización bibliográfica del LPSNC en pacintes con VIH destacando principalmente el aporte de los métodos diagnósticos y terapéuticos.

[Recurrent meningiomas with progressive aggressiveness and posterior extracranial extension]. / Meningiomas recidivantes con agresivisad progresiva y posterior extensión extracraneana. Análisis de 2 casos.

Meningiomas are in most cases benign tumors. They represent about 15% of primitive intracranial tumors. Complete surgical resection achieves healing in the majority of patients. Recurrences occur in 9 to 12% in spite of that kind of surgical resection in the initial approach. This percentage rises to 40% when removing was not complete. Recurrences sometimes show histological changes into aggressiveness, and even malignization. Two cases of originally benign meningiomas with several recurrences and progressive aggressive behaviour are presented. Both cases led to extracranial extension of the lesions, even passing through synthetic dural grafts (De Bakey's Dacron Fabric-Elastic) and the Titanium mesh covering the craniectomy.

Meningiomas recidivantes con agresividad progresiva y posterior extensión extracraneana. Análisis de 2 casos / Recurrent meningiomas with progressive aggressiviness and posterior extracranial extension

Los meningiomas son tumores mayoritariamente benignos. Representan aproximadamente el 15 por ciento de los tumores intracraneanos primitivos. La exéresis quirúrgica macroscópicamente completa de los mismos, lleva en sí la posibilidad de la curación definitiva.A pesar de ello, las recidivas se comprueban entre un 9 por ciento y un 12 por ciento de los casos, después de las resecciones de este tipo, en la operación inicial. Este porcentaje sube al 40 por ciento en casos de exéresis no totales. Las recidivas pueden tener cambios histológicos hacia la agresividad, e incluso malignizarse.Se presentan dos casos de meningiomas originalmente benignos, con varias recidivas y agresividad progresiva, que llevaron en ambos a una extensión extracraneana de las lesiones, traspasando incluso plastias durales sintéticas (Dacron "Fabric Elastic de De Bakey"), y la malla de titanio que cubría la craniectomía. (AU)

[Cytomegalovirus encephalitis in an immunocompetent patient: clinical, neuropathological and ultrastructural analysis]. / Encefalitis a citomegalovirus en un paciente inmunocompetente: análisis clinico, neuropatologico y ultraestructural.

Cytomegalovirus encephalitis is rarely diagnosed in immunocompetent patients. It is more frequent among immunocompromised hosts. We present a case of a young male patient without evidence of immunosupression who had a cytomegalovirus encephalitis. The diagnosis was made by detection of viral DNA in cerebral tissue obtained by biopsy. Neuropathologic and ultrastructural changes are described and compared with the descriptions in immunocompromised patients.

Normal serum proteins in female breast carcinomas and fibroadenomas. An immunohistochemical study.

Several serum proteins were immunohistochemically studied in benign and malignant breast lesions in 13 patients. The majority of infiltrating duct and lobular carcinomas showed albumin and IgG abundant immune reactive cells. Fewer cells contained immune reactive alpha-1-antitrypsin and transferrin. Staining was diffuse and limited to the cell cytoplasm. Immune reactive cells alternated with non reactive ones in a characteristic heterogeneous pattern. The parenchymal cells in carcinomas were non reactive to ceruloplasmin, fibrinogen and alphafetoprotein. Myoepithelial and epithelial cells in fibroadenomas were also positive for albumin and IgG, but less frequently for alpha-1-antitrypsin and transferrin. Normal breast tissue surrounding fibroadenomas as well as a lactational adenoma showed no immune reactive cells. Mechanisms that may be involved with the presence of plasma proteins in the cytoplasm of parenchymal cells in breast lesions are discussed.

Enfermedad de membrana hialina en recien nacidos con pulmón bioquimicamente maduro / Hyaline membrane disease in newborn infants with biochemically mature lung

clínica, la radiología y la anatomía patológica en forma similar a la EMH

The cytologic diagnosis of hydatid disease.

Eleven cases of hydatid disease diagnosed by cytologic methods are reported. sputum specimens and aspirated peritoneal material were embedded in paraffin and then processed by conventional procedures. Smears were obtained from pleural and ascitic fluids. Sputum cytology gave 33% positive results. The total rate of positive cytology in all echinococosis cases, including sputum, peritoneal material and pleural fluids, was 40%. Silver methenamine and Best carmine procedures were of special interest for the identification of laminated layer fragments.

Angiodisplasia del colon derecho. Diagnostico angiografico y anatomopatologico. / Angiodysplasia of right colon. Angiographic and anatomo-pathological diagnosis

La angiodisplasia de colon se ha reportado como una afeccion frecuente y causa de sangrados gastrointestinales inexplicados. Nuestro interes es exponer los elementos diagnosticos angiograficos y anatomopatologicos, a traves de 2 casos. Debe senalarse que el diagnostico se hace casi exclusivamente a traves de la arteriografia mesenterica y su confirmacion anatomo-patologica exige tecnicas especiales y sobre todo una coordinacion entre el Cirujano, Radiologo y Anatomopatologico para el manejo correcto de la pieza anatomica