No abstract

The von Economo neurons (VEN) are characterized by a large soma, spindle-like soma, with little dendritic arborization at both, the basal and apical poles. In humans, VENs have been described in the entorhinal cortex, the hippocampal formation, the anterior cingulate cortex, the rostral portion of the insula and the dorsomedial Brodmann’s area 9 (BA9). These cortical regions have been associated with cognitive functions such as social interactions, intuition and emotional processing. Previous studies that searched for the presence of these cells in the lateral frontal poles yielded negative results. The presence of VENs in other cortical areas on the medial surface of the human prefrontal cortex which share both a common functional network and similar laminar organization, led us to examine its presence in the medial portion of the frontal pole. In the present study, we used tissue samples from five postmortem subjects taken from the polar portion of BA10, on the medial surface of both hemispheres. We found VENs in the human medial BA10, although they are very scarce and dispersed. We also observed crests and walls of the gyrus to quantitatively assess: (A) interhemispheric asymmetries, (B) the VENs/pyramidal ratio, (C) the area of the soma of VENs and (D) the difference in soma area between VENs and pyramidal and fusiform cells. We found that VENs are at least seven times more abundant on the right hemisphere and at least 2.5 times more abundant in the crest than in the walls of the gyrus. The soma size of VENs in the medial frontopolar cortex is larger than that of pyramidal and fusiform cells of layer VI, and their size is larger in the walls than in the crests. Our finding might be a contribution to the understanding of the role of these neurons in the functional networks in which all the areas in which they have been found are linked. However, the particularities of VENs in the frontal pole, as their size and quantity, may also lead us to interpret the findings in the light of other positions such as van Essen’s theory of tension-based brain morphogenesis.

Traumatic brain injury (TBI) produces several cellular changes, such as gliosis, axonal and dendritic plasticity, and inhibition-excitation imbalance, as well as cell death, which can initiate epileptogenesis. It has been demonstrated that dysfunction of the inhibitory components of the cerebral cortex after injury may cause status epilepticus in experimental models; we proposed to analyze the response of cortical interneurons and astrocytes after TBI in humans. Twelve contusion samples were evaluated, identifying the expression of glial fibrillary acidic protein (GFAP) and calcium-binding proteins (CaBPs). The study was made in sectors with and without preserved cytoarchitecture evaluated with NeuN immunoreactivity (IR). In sectors with total loss of NeuN-IR the results showed a remarkable loss of CaBP-IR both in neuropil and somata. In sectors with conserved cytoarchitecture less drastic changes in CaBP-IR were detected. These changes include a decrease in the amount of parvalbumin (PV-IR) neurons in layer II, an increase of calbindin (CB-IR) neurons in layers III and V, and an increase in calretinin (CR-IR) neurons in layer II. We also observed glial fibrillary acidic protein immunoreactivity (GFAP-IR) in the white matter, in the gray-white matter transition, and around the sectors with NeuN-IR total loss. These findings may reflect dynamic activity as a consequence of the lesion that is associated with changes in the excitatory circuits of neighboring hyperactivated glutamatergic neurons, possibly due to the primary impact, or secondary events such as hypoxia-ischemia. Temporal evolution of these changes may be the substrate linking severe cortical contusion and the resulting epileptogenic activity observed in some patients.

Early life stress can be caused by acute or chronic exposure to childhood events, such as emotional, physical, sexual abuse, and neglect. Early stress is associated with subsequent alterations in physical and mental health, which can extend into adolescence, adulthood, and even old age. The effects of early stress exposure include alterations in cognitive, neuropsychological, and behavioral functions, and can even lead to the development of psychiatric disorders and changes in brain anatomy. The present manuscript provides a review of the main findings on these effects reported in the scientific literature in recent decades. Early life stress is associated with the presence of psychiatric disorders, mainly mood disorders such as depression and risk of suicide, as well as with the presence of post-traumatic stress disorder. At the neuropsychological level, the involvement of different mental processes such as executive functions, abstract reasoning, certain memory modalities, and poor school-skill performance has been reported. In addition, we identified reports of alterations of different subdomains of each of these processes. Regarding neuroanatomical effects, the involvement of cortical regions, subcortical nuclei, and the subcortical white matter has been documented. Among the telencephalic regions most affected and studied are the prefrontal cortex, the hippocampus, the amygdala, and the anterior cingulate cortex. Understanding the impact of early life stress on postnatal brain development is very important for the orientation of therapeutic intervention programs and could help in the formulation and implementation of preventive measures as well as in the reorientation of research targets.

The principal aim in the management of patients with cerebral contusion (CC) following severe traumatic brain injury (TBI) is the prevention, amelioration, and treatment of secondary neuronal dysfunction and pathology. Distinguishing between irreversibly damaged and surviving tissue could have considerable therapeutic and prognostic implications for patients. To characterize structurally the neuronal compartment of the contused region in samples derived from patients who suffered severe TBI and were subjected to decompressive craniectomy, we used NeuN, a neuronal marker. We determined that NeuN "patches", sectors with loss of NeuN immunoreactivity (NeuN-IR), represented 25% of the area among the analyzed cases. We also found a 67% decrease in NeuN levels via Western blot. Tissue adjoining patches of NeuN-IR were considered "preserved" due to the apparent normal density of neurons and conservation of the six cortical layers. Nevertheless, these sectors retained only 39% of their neurons with the classical pattern described for normal NeuN-IR. Using Fluorojade we identified a 16-fold increase in density of moribund neurons in "preserved" sectors when compared to controls. Additionally these abnormalities were enhanced 5-fold in "patches" of NeuN-IR when compared to preserved regions. Therefore, NeuN/Fluorojade abnormalities are indicative of different cell fates characteristic of CC tissue. This analysis addressed exclusively the neuronal compartment and provides new insights into the degenerative state of neurons in the contused region that is likely to contribute to clinical outcome and differentiate TBI from ischemia.

Von Economo neurons (VENs) have been mentioned in the medical literature since the second half of the 19th century; however, it was not until the second decade of the 20th century that their cytomorphology was described in detail. To date, VENs have been found in limbic sectors of the frontal, temporal and insular lobes. In humans, their density seems to decrease in the caudo-rostral and ventro-dorsal direction; that is, from the anterior regions of the cingulate and insular cortices towards the frontal pole and the superior frontal gyrus. Several studies have provided similar descriptions of the shape of the VEN soma, but the size of the soma varies from one cortical region to another. There is consensus among different authors about the selective vulnerability of VENs in certain pathologies, in which a deterioration of the capacities involved in social behaviour is observed. In this review, we propose that the restriction of VENs towards the sectors linked to limbic information processing in Homo sapiens gives them a possible functional role in relation to the structures in which they are located. However, given the divergence in characteristics such as location, density, size and biochemical profile among VENs of different cortical sectors, the activities in which they participate could allow them to partake in a wide spectrum of neurological functions, including autonomic responses and executive functions.

Background: Prefrontal cortex (PFC) represents the highest level of integration and control of psychic and behavioral states. Several dysfunctions such as autism, hyperactivity disorders, depression, and schizophrenia have been related with alterations in the prefrontal cortex (PFC). Among the cortical layers of the PFC, layer II shows a particular vertical pattern of organization, the highest cell density and the biggest non-pyramidal/pyramidal neuronal ratio. We currently characterized the layer II cytoarchitecture in human areas 10, 24, and 46. Objective: We focused particularly on the inhibitory neurons taking into account that these cells are involved in sustained firing (SF) after stimuli disappearance.Methods: Postmortem samples from five subjects who died by causes different to central nervous system diseases were studied. Immunohistochemistry for the neuronal markers, NeuN, parvalbumin (PV), calbindin (CB), and calretinin (CR) were used. NeuN targeted the total neuronal population while the rest of the markers specifically the interneurons.Results: Cell density and soma size were statically different between areas 10, 46, 24 when using NeuN. Layer II of area 46 showed the highest cell density. Regarding interneurons, PV+-cells of area 46 showed the highest density and size, in accordance to the proposal of a dual origin of the cerebral cortex. Interhemispheric asymmetries were not identified between homologue areas.Conclusion: First, our findings suggest that layer II of area 46 exhibits the most powerful inhibitory system compared to the other prefrontal areas analyzed. This feature is not only characteristic of the PFC but also supports a particular role of layer II of area 46 in SF. Additionally, known functional asymmetries between hemispheres might not be supported by morphological asymmetries.

Neurodevelopmental disorders (NDDs) are conditions that present with brain dysfunction due to alterations in the processes of brain development. They present with neuropsychiatric, cognitive, and motor symptoms. Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are two of the most common NDDs. Human brain tissue is a scarce resource that is obtained from postmortem donations. In the case of NDDs, specifically autism, the reduced donation rate of brains prevents researchers to investigate its pathology and fine anatomy. The Hispano-American Brain Bank of Neurodevelopmental Disorders (Banco Hispanoamericano de CErebros de trastornos del NEurodesarrollo) or CENE is a large-scale brain bank for neurodevelopmental disorders in Hispano-America and the US. CENE's objectives are to collect and distribute brains of patients with NDDS, with a focus on ASD and FXS, to perform research, promote education of future scientists, and enhance public awareness about the importance of human tissue availability for scientific research on brain function and disease. CENE has thus far established a bilingual system of nodes and teams in several American countries including California-