[Identification of risk factors for congenital malformations]. / Factores de riesgo de ocurrencia y gravedad de malformaciones congénitas.

BACKGROUND: The relative importance of congenital malformations as a cause of death in the first year of life is increasing along with the control of preventable causes of perinatal mortality. AIM: To identify risk factors for congenital malformations. PATIENTS AND METHODS: Retrospective case-control study of births registered in the database of The Latin American Collaborative Study of Congenital Malformations (ECLAMC), in the period 2001-2010. RESULTS: Birth weight and gestational age were significantly lower in cases than controls, behaving as risk factors and associated with a greater severity of congenital malformations. The risk and severity of congenital malformations increased along with mother's age. Fetal growth retardation, a history of congenital malformations in the family, physical factors and acute illnesses of the mother in the first trimester of pregnancy were also significant risk factors for congenital malformations and their severity. The educational level of the mother was a protective factor for congenital malformations and their severity. CONCLUSIONS: Variables previously identified as risk factors for congenital malformations, were significantly related with the occurrence of congenital malformations and their severity.

The nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: a PET, histological and biochemical study.

Parkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET ((18)F-DOPA K(i) and (11)C-DTBZ binding potential), as well as with TH-immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features.

Resultado de los primeros 2 años de implementación de un protocolo ERAS o STAR (eSTrategias para Adelantar la Recuperación) en un hospital público de Chile

Introducción: Las herramientas que han demostrado ser más eficaces en el manejo perioperatorio, corresponden a los protocolos ERAS o STAR (eSTrategias para Adelantar la Recuperación) como nombre local. Objetivo: Describir los resultados obtenidos luego de 2 años de implementación del protocolo STAR en estadía hospitalaria, complicaciones y reingresos. Objetivo secundario describir adherencia al protocolo. Material y Método: Estudio de cohorte retrospectivo no concurrente, en cirugía colorrectal electiva. Enero-diciembre 2016 manejo no protocolizado (grupo no-STAR), agosto 2018 a julio 2020 manejo protocolo STAR (grupo STAR). Registro de variables demográficas, adherencias, complicaciones y reingreso. Se utilizaron variables continuas (cuartiles, promedio y DE), test t-Student, test de Wilcoxon, variables categóricas (frecuencias y porcentajes), test de Fisher y Propensisty Score (PS). Resultados: 239 pacientes; grupo no-STAR 85 pacientes (35,5%), grupo STAR 154 (64,5%), sexo masculino 111 pacientes (43 no-STAR p = 0,347). Promedio edad no-STAR 64,2 (SD 14,7) vs. STAR 66,3 (SD 14,39) (p = 0,3147). Mediana de estadía no-STAR 5 días (promedio 6,9, SD 6,2) y STAR 3 días (promedio 4,8 días, SD 4,4). No-STAR tuvo 22 complicaciones (25,9%) vs 28 STAR (18,2%) p = 0,185. No-STAR 7 reingresos vs 17 STAR (p = 0,654). Análisis de covarianza días de hospitalización ajustado por sexo, edad y cirugía laparoscópica, grupo STAR produce 1,93 días menos de hospitalización (p = 0,005) y PS disminuye en 1,92 días la estadía hospitalaria (p-value = 0,007). Discusión y Conclusión: La implementación de un protocolo de recuperación avanzada logra la reducción de 2 días en la estadía hospitalaria de los pacientes sometidos a una cirugía colorrectal, sin aumentar complicaciones, mortalidad ni reingresos.

Introduction: >Enhanced recovery after Surgery (ERAS) or STAR are the tools that have proven to be more effective in perioperative management. Objective: Primary objective is to describe the results obtained regarding complications, hospital stay and readmissions after 2 years of implementation of the STAR. Secondary objective is to describe protocol adherence. Materials and Method: Non-concurrent retrospective cohort study, in patients with elective colorectal surgery. From January to December 2016 non-protocolized management (non-STAR group), August 2018 to July 2020 STAR protocol management (STAR group). Registration of data like the demographic variables, adherence to protocol, complications and readmissions. Continuous variables (quartiles, mean and SD), t-Student test, Wilcoxon test, categorical variables (frequencies and percentages), Fisher test and propensity score (PS) were used. Results: 239 patients; non-STAR group 85 patients (35.5%), STAR group 154 (64.5%), male 111 patients (43 non-STAR p = 0.347). Average age non-STAR 64.2 (SD 14.7) vs STAR 66.3 (SD 14.39) (p = 0.3147). Median non-STAR stays 5 days (average 6.9, SD 6.2) and for STAR 3 days (average 4.8 days, SD 4.4). Non-STAR had 22 complications (25.9%) vs 28 STAR (18.2%) p = 0.185. No-STAR 7 hospital readmissions vs 17 STAR (p = 0.654). Analysis of covariance (ANCOVA) for hospitalization days adjusted by gender, age and laparoscopic surgery shows 1.93 less hospitalization days (p = 0.005); Propensity Score (PS) shows reduced hospital stay in 1.92 days (p-value = 0.007). Discussion and Conclusión: The implementation of an advanced recovery protocol achieves a reduction of 2 days in the hospital stay of patients undergoing colorectal surgery, without increasing complications, mortality or readmissions.

Effect of External Irrelevant Distracters on a Visual Search Test in School-Age Children: Computerized Assessment.

OBJECTIVE: This study aimed to test the effect of an irrelevant external distracter included in a computer-administered visual search test. Two hypotheses were tested: (a) If the distracter affects performance, attention efficiency will be lowered; (b) if children do not habituate to the distracter, performance will be lower for every item of the test. METHOD: Distraction was induced changing the screen color unexpectedly several times in each trial-450 children (225 girls and 225 boys) from second to sixth course were tested. This group was compared with a group of 423 children from the same age range who were tested with the same test without distraction. RESULTS: Induced distraction reduced attention efficiency for all ages and for every trial in the treatment group (test with distraction). Speed was lower, but number of errors did not increase. CONCLUSION: School-age children cope with an irrelevant external distracter by reducing speed, not accuracy.

Caracterización de lesiones duodenales y su sobrevida / Characterization of duodenal lesions and their survival

Resumen Introducción: Las lesiones duodenales son infrecuentes. Objetivo: Caracterizar a los pacientes con lesiones duodenales observados entre enero de 2008 y diciembre de 2013 en el Servicio de Salud Metropolitano Sur, en Santiago de Chile. Materiales y Método: Se obtuvieron los datos de los registros del Hospital Barros Luco Trudeau y Hospital El Pino. Los pacientes incluidos fueron los observados entre enero de 2008 y diciembre de 2013. Se analizaron edad, género, características clínicas, localización, métodos diagnósticos, hallazgos anatomopatológicos y tratamiento. El 24 de abril de 2019 se obtuvo la fecha de fallecimiento de todos los pacientes del Registro Civil. El análisis estadístico se realizó con el software STATA 15.1. Resultados: Se encontraron 157 pacientes con lesiones duodenales, 65 presentaron adenocarcinoma duodenal y 71 pacientes pólipos duodenales, 25 de ellos fueron adenomas. Análisis univariado de sobrevida evidenció que los pacientes con pólipos asociado a carcinoma y los adenocarcinomas duodenales, presentaron una sobrevida inferior (p = 0,013, HR 6,584 y p < 0,001, HR 7,604, respectivamente). En los pacientes con adenocarcinoma duodenal, aquellos que se sometieron a una cirugía con intención curativa, y aquellos que recibieron quimioterapia tuvieron una sobrevida global mejor que aquellos que no recibieron terapia (p < 0,001, HR 0,351 y p = 0,001, HR 0,276, respectivamente. Discusión: La incidencia estimada del adenocarcinoma duodenal en nuestra población es de 1,1 por cada 100.000 habitantes, la que es más alta que otras publicadas. Proponemos estudio endoscópico en poblaciones de riesgo y tratamiento con intención curativa para los pacientes con adenocarcinoma duodenal sin metástasis a distancia.

Introduction: Duodenal lesions are infrequent. Aim: To characterize patients with duodenal lesions observed between January 2008 and December 2013 at the Southern Metropolitan Health Service, in Santiago, Chile. Materials and Method: Data were obtained from the Barros Luco Trudeau Hospital and El Pino Hospital records. The patients included were those observed between January 2008 and December 2013. Age, gender, clinical characteristics, location, diagnostic methods, anatomopathological findings and treatment were analyzed. On April 24th 2019 was obtained the date of death of all patients at the National Civil Registry. The statistical analysis was performed with the software STATA 15.1. Results: 157 patients with duodenal lesions were found, 65 presented duodenal adenocarcinoma and 71 patients had duodenal polyps, 25 of them were adenomas. Univariate analysis of survival showed that patients with polyps associated with carcinoma and duodenal adenocarcinomas had a lower survival rate (p = 0.013, HR 6.584 y p < 0.001, HR 7.604, respectively). In patients with duodenal adenocarcinoma, those who underwent surgery with curative intent, and those who receive chemotherapy had a better overall survival than those who did not received therapy (p < 0.001, HR 0.351 y p = 0.001, HR 0.276, respectively). Discussion: We propose endoscopic study in at-risk populations and treatment with curative intent for patients with duodenal adenocarcinoma without distant metastases. The estimated incidence of duodenal adenocarcinoma in our population is 1.1 per 100,000 inhabitants and seem to be higher than other published.

Posterior parietal cortex in rhesus monkey: I. Parcellation of areas based on distinctive limbic and sensory corticocortical connections.

Injections of HRP-WGA in four cytoarchitectonic subdivisions of the posterior parietal cortex in rhesus monkeys allowed us to examine the major limbic and sensory afferent and efferent connections of each area. Area 7a (the caudal part of the posterior parietal lobe) is reciprocally interconnected with multiple visual-related areas: the superior temporal polysensory area (STP) in the upper bank of the superior temporal sulcus (STS), visual motion areas in the upper bank of STS, the dorsal prelunate gyrus, and portions of V2 and the parieto-occipital (PO) area. Area 7a is also heavily interconnected with limbic areas: the ventral posterior cingulate cortex, agranular retrosplenial cortex, caudomedial lobule, the parahippocampal gyrus, and the presubiculum. By contrast, the adjacent subdivision, area 7ip (within the posterior bank of the intraparietal sulcus), has few limbic connections but projects to and receives projections from widespread visual areas different than those that are connected with area 7a: the ventral bank and fundus of the STS including part of the STP cortex and the inferotemporal cortex (IT), areas MT (middle temporal) and possibly MTp (MT peripheral) and FST (fundal superior temporal) and portions of V2, V3v, V3d, V3A, V4, PO, and the inferior temporal (IT) convexity cortex. The connections between posterior parietal areas and visual areas located on the medial surface of the occipital and parieto-occipital cortex, containing peripheral representations of the visual field (V2, V3, PO), represent a major previously unrecognized source of visual inputs to the parietal association cortex. Area 7b (the rostral part of the posterior parietal lobe) was distinctive among parietal areas in its selective association with somatosensory-related areas: S1, S2, 5, the vestibular cortex, the insular cortex, and the supplementary somatosensory area (SSA). Like 7ip, area 7b had few limbic associations. Area 7m (on the medial posterior parietal cortex) has its own topographically distinct connections with the limbic (the posterior ventral bank of the cingulate sulcus, granular retrosplenial cortex, and presubiculum), visual (V2, PO, and the visual motion cortex in the upper bank of the STS), and somatosensory (SSA, and area 5) cortical areas. Each parietal subdivision is extensively interconnected with areas of the contralateral hemisphere, including both the homotopic cortex and widespread heterotopic areas. Indeed, each area is interconnected with as many areas of the contralateral hemisphere as it is within the ipsilateral one, though less intensively. This pattern of distribution allows for a remarkable degree of interhemispheric integration.(ABSTRACT TRUNCATED AT 400 WORDS)

Posterior parietal cortex in rhesus monkey: II. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe.

We have examined the circuitry connecting the posterior parietal cortex with the frontal lobe of rhesus monkeys. HRP-WGA and tritiated amino acids were injected into subdivisions 7m, 7a, 7b, and 7ip of the posterior parietal cortex, and anterograde and retrograde label was recorded within the frontal motor and association cortices. Our main finding is that each subdivision of parietal cortex is connected with a unique set of frontal areas. Thus, area 7m, on the medial parietal surface, is interconnected with the dorsal premotor cortex and the supplementary motor area, including the supplementary eye field. Within the prefrontal cortex, area 7m's connections are with the rostral sector of the frontal eye field (FEF), the dorsal bank of the principal sulcus, and the anterior bank of the inferior arcuate sulcus (Walker's area 45). In contrast, area 7a, on the posterior parietal convexity, is not linked with premotor regions but is heavily interconnected with the rostral FEF in the anterior bank of the superior arcuate sulcus, the dorsolateral prefrontal convexity, the rostral orbitofrontal cortex, area 45, and the fundus and adjacent cortex of the dorsal and ventral banks of the principal sulcus. Area 7b, in the anterior part of the posterior parietal lobule, is interconnected with still a different set of frontal areas, which include the ventral premotor cortex and supplementary motor area, area 45, and the external part of the ventral bank of the principal sulcus. The prominent connections of area 7ip, in the posterior bank of the intraparietal sulcus, are with the supplementary eye field and restricted portions of the ventral premotor cortex, with a wide area of the FEF that includes both its rostral and caudal sectors, and with area 45. All frontoparietal connections are reciprocal, and although they are most prominent within a hemisphere, notable interhemispheric connections are also present. These findings provide a basis for a parcellation of the classically considered association cortex of the frontal lobe, particularly the cortex of the principal sulcus, into sectors defined by their specific connections with the posterior parietal subdivisions. Moreover, the present findings, together with those of a companion study (Cavada and Goldman-Rakic: J. Comp. Neurol. this issue) have allowed us to establish multiple linkages between frontal areas and specific limbic and sensory cortices through the posterior parietal cortex. The networks thus defined may form part of the neural substrate of parallel distributed processing in the cerebral cortex.

Topographical organization of the cortical afferent connections of the prefrontal cortex in the cat.

The topographical distribution of the cortical afferent connections of the prefrontal cortex (PFC) in adult cats was studied by using the retrograde axonal transport of horseradish peroxidase technique. Small single injections of the enzyme were made in different locations of the PFC, and the areal location and density of the subsequent neuronal labeling in neocortex and allocortex were evaluated in each case. The comparison of the results obtained in the various cases revealed that four prefrontal sectors (rostral, dorsolateral, ventral, and dorsomedial) can be distinguished, each exhibiting a particular pattern of cortical afferents. All PFC sectors receive projections from the ipsilateral insular (agranular and granular subdivisions) and limbic (infralimbic, prelimbic, anterior limbic, cingular, and retrosplenial areas) cortices. These cortices provide the most abundant cortical projections to the PFC, and their various subdivisions have different preferential targets within the PFC. The premotor cortex and the following neocortical sensory association areas project differentially upon the various ipsilateral PFC sectors: the portion of the somatosensory area SIV in the upper bank of the anterior ectosylvian sulcus, the visual area in the lower bank of the same sulcus, the auditory area AII, the temporal area, the perirhinal cortex, the posterior suprasylvian area, area 20, the posterior ectosylvian area, the suprasylvian fringe, the lateral suprasylvian area (anterolateral and posterolateral subdivisions), area 5, and area 7. The olfactory peduncle, the prepiriform cortex, the cortico-amygdaloid transition area, the entorhinal cortex, the subiculum (ventral, posteroventral, and posterodorsal sectors), the caudomedial band of the hippocampal formation and the postsubiculum are the allocortical sources of afferents to the PFC. The dorsolateral PFC sector is the target of the largest insular, limbic, and neocortical sensory association projections. The dorsomedial and rostral sectors receive notably less abundant cortical afferents than the dorsolateral sector. Those to the dorsomedial sector arise from the same areas that project to the dorsolateral sector and are more abundant to the dorsal part, where the medial frontal eye field cortex is located. The rostral sector receives projections principally from all other PFC sectors, and from the limbic and insular cortices. The projections from the allocortex reach preferentially the ventral PFC sector. Intraprefrontal connections are most abundant within each PFC sector. Commissural interprefrontal connections are largest from the site homotopic to the HRP injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic innervation of the monkey thalamus: an immunohistochemical study.

The distribution and function of the neurotransmitter adrenaline in the primate brain are poorly understood. Biochemical studies have shown the presence of adrenaline or its biosynthetic enzyme, phenylethanolamine-N-methyltransferase, in the rat and human thalamus. However, the distribution of the adrenergic fibres in the thalamus has only been demonstrated in rats. We study the adrenergic innervation of the macaque monkey thalamus using immunohistochemistry against phenyletanolamine-N-methyltransferase. The distribution of phenyletanolamine-N-methyltransferase-immunoreactive fibres is markedly heterogeneous and principally restricted to those nuclei, or their portions, that are located in or close to the midline, with the highest density being found in the paraventricular, parafascicular and mediodorsal nuclei. The paraventricular nucleus is densely innervated by adrenergic axons throughout, while the densest innervation of the parafascicular nucleus is located in its medial part and the strongest mediodorsal nuclear immunolabelling is found in its most posterior and medial region. Moderate or low concentrations of phenyletanolamine-N-methyltransferase-immunopositive fibres are present in the paratenial nucleus, and all parts of the central nucleus, nucleus reuniens, central medial nucleus, centromedian nucleus, medial geniculate body and medial pulvinar nucleus, while only scattered immunoreactive axons are found in other thalamic nuclei. The morphology of the phenyletanolamine-N-methyltransferase-immunoreactive axons is quite diverse, as they have different diameters and most are endowed with diversely-shaped varicosities. These findings are the first morphological evidence for the presence of adrenergic innervation in the primate thalamus and reveal that this innervation is highly selective, heterogeneous and more widely distributed in primates than in rats. The thalamic nuclei innervated by adrenaline are connected to widespread limbic and associative cortical areas as well as to subcortical structures, in particular the neostriatum and amygdala. We hypothesize that thalamic adrenaline may be implicated in emotional, social and attentional mechanisms through its facilitation of co-ordinated action by these brain regions.

Topographic segregation of corticostriatal projections from posterior parietal subdivisions in the macaque monkey.

The distribution of corticostriatal projections from areas 7m, 7a, 7b and 7ip of the posterior parietal cortex was studied in rhesus monkeys using horseradish peroxidase conjugated with wheat-germ agglutinin as an anterograde tracer. All parietal subdivisions project bilaterally over a broad anteroposterior expanse of the caudate nucleus and putamen; however, the zones of densest terminal labeling varied for each parietal subdivision. Thus, area 7m projects preferentially to dorsal and dorsolateral portions of the head and anterior part of the body of the caudate nucleus. The main striatal target of area 7a is also in the head and anterior portion of the body of the caudate nucleus, but at dorsal and dorsomedial zones. The preferential target region of area 7ip in the striatum is in the posterior two-thirds of the body of the caudate nucleus, where the labeled terminals spare only the medial border. In contrast to the other parietal subdivisions, 7b projects preferentially to the putamen. In this nucleus, the location of labeling after 7b injections appears to correspond to the zones containing the representations of the distal forelimb and head. Each parietal subdivision projects to a rather extended anteroposterior domain in the contralateral neostriatum, the projection zones being always less extensive than in the ipsilateral side, but with a similar topographic distribution. Because we have shown previously that each parietal subdivision is part of a distinct distributed corticocortical network, the neostriatal territories innervated by each subdivision can be correlated with the corresponding network, thus providing insight into the functional specializations of the striatum.

Acetylcholinesterase histochemistry in the macaque thalamus reveals territories selectively connected to frontal, parietal and temporal association cortices.

The patterns of histochemical staining for acetylcholinesterase (AChE) activity in the macaque thalamus were analyzed and compared with the distribution of cells and terminals labeled from injections of axonal tracers in the dorsolateral and orbital prefrontal cortex, in area 7a of the posterior parietal cortex and in the polysensory cortex of the superior temporal sulcus. AChE histochemistry is very useful in delineating the thalamic nuclei connected with the association cortex and in uncovering thalamic subdivisions that are barely evident on cytoarchitectonic grounds. Moreover, AChE activity reveals previously unrecognized heterogeneities within several thalamic nuclei, like the ventral anterior (VA), where a new ventromedial subdivision (VAvm) is described, the medial pulvinar (PulM) or the mediodorsal nucleus (MD). In this nucleus three distinct chemical domains are present: the medial, ventral and lateral sectors characterized by low, moderate and high AChE activities, respectively. The staining pattern of the lateral sector is markedly heterogeneous with patches of intense AChE activity surrounded by a moderately stained matrix. The MD medial sector is connected with the orbitofrontal cortex, whereas the AChE-rich patches in the lateral sector are selectively connected with the dorsolateral prefrontal, parietal and temporal association cortices. In the PulM, a dorsomedial AChE-rich patch is selectively connected with the orbitofrontal cortex, whereas the surrounding territory, which shows moderate AChE activity, is preferentially connected with the parietal and temporal cortices. Chemically specific domains in the anterior, ventral anterior, midline, and intralaminar thalamic nuclei are also connected with the examined association cortices. These findings indicate that the topographic patterns of the thalamo-cortical connections of primate association areas conform to the chemical architecture of the thalamus. This implies that because each cortical area is connected to a particular set of thalamic regions, the influence of the thalamus on cortical function is exclusive for each area, highly diverse among the various association areas, and subject to a wide range of modulation at the thalamic level.

The lateral geniculate nucleus projects to the inferior temporal cortex in the macaque monkey.

The dorsal lateral geniculate nucleus of the thalamus (dLGN) projects to several extrastriate areas of the macaque brain. The extent of the dLGN projection to the visual temporal cortex was investigated using retrogradely transported dyes. A population of dLGN neurones was labelled after injections in the inferior temporal cortex (ITC) including the lower bank of the superior temporal sulcus and the inferior temporal convexity. The labelled neurons were located in the lateral half of the posterior one-third of the dLGN and predominated in the interlaminar zones or close to the borders of the parvocellular layers. This direct projection from the dLGN to the ITC may mediate some of the visual abilities known to be retained by destriated animals.

Intrahemispheric cortico-cortical afferent connections of the prefrontal cortex in the cat.

Ipsilateral cortical projections to the prefrontal cortex of the cat were investigated by means of the retrograde axonal transport of horseradish peroxidase technique. Labeled neurons were identified in frontal, insular, parietal and temporal regions, as well as in cingular, retrosplenial and perirhinal areas. These intrahemispheric cortical connections can be compared to those described in the rhesus monkey.

Afferent connections of area 20 in the cat studied by means of the retrograde axonal transport of horseradish peroxidase.

Following injections of horseradish peroxidase in area 20 of the cat neuronal labeling was observed in visual areas 19, 21 and lateral suprasylvian as well as in other sensory, association and limbic related neo- and allocortical regions, both ipsi- and contralaterally. Labeled neurons in the thalamus were identified in the LP-Pu complex, in the LIc, in the midline and intralaminar nuclei, and in the nuclei ventralis anterior, dorsalis medialis, lateralis anterior, lateralis medialis, ventralis posteroinferior, and in the medial subdivision of the posterior group. Projections from other subcortical prosencephalic and brain stem regions are also described.

Retrograde double labeling of neurons: the combined use of horseradish peroxidase and diamidino yellow dihydrochloride (DY X 2HCl) compared with true blue and DY X 2HCl in rat descending brainstem pathways.

Three series of double-labeling experiments were carried out in a study of the collateralization of brainstem nuclei which project to the spinal cord in the rat. The fluorescent tracer Diamidino Yellow Dihydrochloride (DY X 2HCl) was injected in one half of the spinal gray and white matter at T7-T8 or T13-L1. Subsequently, either True Blue (TB), wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) or free HRP were injected ipsilaterally in the gray matter at C5-C8. The distributions of single and double retrogradely labeled neurons were studied in the following cell groups: red nucleus, interstitial nucleus of Cajal, ventrolateral pontine tegmentum, nuclei coeruleus and subcoeruleus and nuclei raphe magnus and raphe pallidus including the adjoining ventral reticular formation. The numbers of TB- or HRP-labeled neurons present in those nuclei were counted and the percentages of double-labeled neurons were calculated when TB or HRP had been used in combination with DY X 2HCl. The results indicate: The HRP-TMB reaction product and the DY X 2HCl fluorescence can be visualized simultaneously in retrogradely single- or double-labeled neurons. The distributions of single- and double-labeled neurons in the various brainstem nuclei were entirely comparable when using TB with DY X 2HCl or HRP with DY X 2HCl. The percentages of double-labeled neurons obtained with HRP and DY X 2HCl were consistent over a series of cases, and were comparable to those obtained with TB and DY X 2HCl in several structures. However, in the red nucleus slightly lower percentages of double-labeled neurons were obtained using HRP and DY X 2HCl as compared with the percentages obtained using TB and DY X 2HCl.

Allocortical afferent connections of the prefrontal cortex in the cat.

Afferent connections of the prefrontal cortex of the cat arising in allocortical regions have been investigated using the horseradish peroxidase retrograde transport technique. Our results demonstrate the existence of projections from the olfactory peduncle, anterior and posterior prepiriform cortices, cortico-amygdaloid transition area, entorhinal cortex, ventral, caudal and dorsal subiculum and postsubiculum to the prefrontal cortex.

Collateralization of brainstem pathways in the spinal ventral horn in rat as demonstrated with the retrograde fluorescent double-labeling technique.

The collateralization of brainstem pathways to the spinal ventral horn was studied in rat by means of injections of True Blue (TB) and Diamidino Yellow Dihydrochloride (DY .2HCl) at different levels in the spinal cord. TB (or DY .2HCl) was injected in the cervical gray and DY .2HCl (or TB) was injected ipsilaterally either at mid-thoracic or at lumbar levels. The retrogradely single- and double-labeled neurons were studied in the interstitial nucleus of Cajal, the lateral vestibular nucleus of Deiters, the nucleus (sub) coeruleus and the nucleus raphe pallidus, including the adjoining ventral medullary reticular formation. In all those brainstem nuclei many double-labeled neurons were present after both mid-thoracic and lumbar injections. This indicates that these brainstem spinal pathways to the ventral horn probably give off many collaterals along their trajectory in the spinal cord.

Interhemispheric cortico-cortical connections to the prefrontal cortex in the cat.

The existence of interhemispheric cortical afferent connections to the prefrontal cortex of the cat is investigated by means of the retrograde axonal transport of horseradish peroxidase technique. Labeled neurons are found in contralateral hemisphere in sites homotopical and heterotopical to the injection. The heterotopical contralateral projection arises principally from prefrontal, insular, prelimbic, premotor, cingular and retrosplenial cortices.

Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice.

Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD) brains. Both patients and mouse models of AD show decreased level of circulating IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma IGF-I. Importantly, in presymptomatic AD mice this reduction is already manifested as a decreased brain input of serum IGF-I in response to environmental enrichment. To explore a potential diagnostic use of this early loss of IGF-I input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice. Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD mice showed blunted ECG responses. Because nonhuman primates showed identically enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD patients.