Regions Of Cerebral Cortex Research Articles

Historical Perspectives on the Behavioral Function of the Insula.

The advent of functional neuroimaging technology has seen increased interest in the behavioral function of the region of cerebral cortex known as the insula. Localization of function for this brain region has been slow to develop as it is rarely affected in isolation by naturally occurring structural brain injury and many of the behaviors with which it has been associated are not measured by traditional neuropsychological tests. While it is widely acknowledged that the name originated with Johann-Christian Reil (1809), who is more famous for coining the term Bpsychiatry^ (Binder et al. 2007) little has been written in the English language literature of historical conceptions of the function of insular cortex. One exception was the pioneering electrical stimulation study of patients treated surgically for focal seizures originating within or near insular cortex at the Montreal Neurological Institute (Penfield and Faulk 1955) that noted: BEarly anatomists and physiologists regarded it diversely as a center for speech (Rose 1928), or for taste (von Bechterew 1899)^ (p. 445). Both references are to papers published in German. Rose (1928) was a comparative cytoarchitectonic study of insular cortex in several species including the bat, hedgehog, lemur, baboon, and human. It is known for the identification of so-called von Economo neurons in the insula (Ŝimic and Hof 2015). In contrast, the reference to von Bechterew (1899) is incorrect. As clarified by Soros (This issue), the early conception of the insula as primary taste cortex should be credited to Gorschkow (1901) who conducted ablation studies on dogs in Bechterew’s laboratory. Primary taste cortex remains the behavioral functionmost commonly attributed to the insula inmodern neuroscience textbooks (e.g., Kolb and Whishaw 2014), even though this brain region is now considered to play a muchmore diverse role in human behavior (Gasquoine 2014).

Essential functions of primate frontopolar cortex in cognition

Brodmann's area 10 is one of the largest cytoarchitecturally defined regions in the human cerebral cortex, occupying the most anterior part of the prefrontal cortex [frontopolar cortex (FPC)], and is believed to sit atop a prefrontal hierarchy. The crucial contributions that the FPC makes to cognition are unknown. Rodents do not possess such [corrected] a FPC, but primates do, and we report here the behavioral effects of circumscribed FPC lesions in nonhuman primates. FPC lesions selectively impaired rapid one-trial learning about unfamiliar objects and unfamiliar objects-in-scenes, and also impaired rapid learning about novel abstract rules. Object recognition memory, shifting between established abstract behavioral rules, and the simultaneous application of two distinct rules were unaffected by the FPC lesion. The distinctive pattern of impaired and spared performance across these seven behavioral tasks reveals that the FPC mediates exploration and rapid learning about the relative value of novel behavioral options, and shows that the crucial contributions made by the FPC to cognition differ markedly from the contributions of other primate prefrontal regions.

Abstract W MP120: Minimally Invasive Subcortical Parafascicular Access for Clot Evacuation. A Paradigm Shift

Introduction: Spontaneous intracerebral hemorrhage (ICH) is common and causes significant mortality and morbidity. To date, intervention remains uncertain. Neurosurgical therapies for subcortical lesions have been limited by procedure-related injury to the cerebral cortex and adjacent subcortical brain regions. This is particularly relevant for eloquent cortex, therefore surgical therapy is often not performed. Hypothesis: We hypothesized that using an integrated systems approach for Minimally invasive Subcortical Parafascicular Access for Clot Evacuation (MiSPACE) consistently, could result in improved clinical outcomes and protection of eloquent tissue, especially if we focus on minimizing trauma to normal tissue. Methods: We report on this standardized technique incorporating 5 cores of MiSPACE 1) image interpretation and trajectory planning, 2) dynamic navigation, 3) a traumatic access (BrainPath, NICO Corp), 4) optics (Storz), and 5) resection (Myriad, NICO, Corp), wherein all surgeons have been trained through a CME course and have applied the surgical technique and approach in all 25 cases. Pathology, pre- and post-operative clinical and radiographic characteristics and clinical outcome at last follow-up were collected. Results and Conclusions: The cases presented illustrate successful application of the MiSPACE standardized systems approach. Mean pre-operative ICH volume was 47.2 and mean percentage of clot removal was 89%. Most importantly, significant recovery was observed in 89% of patients with no new deficits reported. MRI tractography obtained pre operatively illustrates how collateral tissue preservation can be achieved by trajectory planning. Using the same technique, the same equipment, in a standardized approach in dominant, eloquent cortex and subcortical regions (Table 1) this may lead to improved outcomes. Safety and feasibility studies are required to further assess this promising new therapeutic paradigm.

Fatigue sensation following peripheral viral infection is triggered by neuroinflammation: who will answer these questions?

Fatigue sensation following peripheral viral infection is triggered by neuroinflammation: who will answer these questions?

Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats.

The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.

Expression and localization of type II diacylglycerol kinase isozymes δ and η in the developing mouse brain.

The functions of type II diacylglycerol kinase (DGK) δ and -η in the brain are still unclear. As a first step, we investigated the spatial and temporal expression of DGKδ and -η in the brains of mice. DGKδ2, but not DGKδ1, was highly expressed in layers II-VI of the cerebral cortex; CA-CA3 regions and dentate gyrus of hippocampus; mitral cell, glomerular and granule cell layers of the olfactory bulb; and the granule cell layer in the cerebellum in 1- to 32-week-old mice. DGKδ2 was expressed just after birth, and its expression levels dramatically increased from weeks 1 to 4. A substantial amount of DGKη (η1/η2) was detected in layers II-VI of the cerebral cortex, CA1 and CA2 regions and dentate gyrus of the hippocampus, mitral cell and glomerular layers of the olfactory bulb, and Purkinje cells in the cerebellum of 1- to 32-week-old mice. DGKη2 expression reached maximum levels at P5 and decreased by 4 weeks, whereas DGKη1 increased over the same time frame. These results indicate that the expression patterns of DGK isozymes differ from each other and also from other isozymes, and this suggests that DGKδ and -η play distinct and specific roles in the brain.

Bilastine vs. hydroxyzine: occupation of brain histamine H1‐receptors evaluated by positron emission tomography in healthy volunteers

AimA close correlation exists between positron emission tomography (PET)-determined histamine H1-receptor occupancy (H1RO) and the incidence of sedation. Antihistamines with H1RO <20% are classified as non-sedating. The objective was to compare the H1RO of bilastine, a second generation antihistamine, with that of hydroxyzine.MethodsThis randomized, double-blind, crossover study used PET imaging with [11C]-doxepin to evaluate H1RO in 12 healthy males (mean age 26.2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials and H1ROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated.ResultsThe mean binding potential of all five regions of interest (total binding potential) was significantly greater with bilastine than hydroxyzine (mean value 0.26 vs. 0.13, P < 0.01; mean difference and 95% CI −0.130 [−0.155, 0.105]). There was no significant difference between bilastine and placebo. Overall H1RO by bilastine was significantly lower than that by hydroxyzine (mean value −3.92% vs. 53.95%, P < 0.01; mean difference and 95% CI 57.870% [42.664%, 73.075%]). There was no significant linear relationship between individual bilastine plasma concentrations and total binding potential values. No significant between-treatment differences were observed for sedation and psychomotor performance. Twenty-six non-serious AEs were reported. Sleepiness or sedation was not reported with bilastine but appeared in some subjects with hydroxyzine.ConclusionsA single oral dose of bilastine 20 mg had minimal H1RO, was not associated with subjective sedation or objective impairment of psychomotor performance and was devoid of treatment-related sedative AEs, thus satisfying relevant subjective, objective and PET criteria as a non-sedating antihistamine.

Histological correlates of N40 auditory evoked potentials in adult rats after neonatal ventral hippocampal lesion: animal model of schizophrenia

The neonatal ventral hippocampal lesion (NVHL) is an established neurodevelopmental rat model of schizophrenia. Rats with NVHL exhibit several behavioral, molecular and physiological abnormalities that are similar to those found in schizophrenics. Schizophrenia is a severe psychiatric illness characterized by profound disturbances of mental functions including neurophysiological deficits in brain information processing. These deficits can be assessed by auditory evoked potentials (AEPs), where schizophrenics exhibit abnormalities in amplitude, duration and latency of such AEPs. The aim of the present study was to compare the density of cells in the temporal cerebral cortex and the N40-AEP of adult NVHL rats versus adult sham rats. We found that rats with NVHL exhibit significant lower amplitude of the N40-AEP and a significant lower number of cells in bilateral regions of the temporal cerebral cortex compared to sham rats. Because the AEP recordings were obtained from anesthetized rats, we suggest that NVHL leads to inappropriate innervation in thalamic-cortical pathways in the adult rat, leading to altered function of cortical networks involved in processing of primary auditory information.

Brain distribution of dipeptide repeat proteins in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72.

A hexanucleotide (GGGGCC) expansion in C9ORF72 gene is the most common genetic change seen in familial Frontotemporal Lobar Degeneration (FTLD) and familial Motor Neurone Disease (MND). Pathologically, expansion bearers show characteristic p62 positive, TDP-43 negative inclusion bodies within cerebellar and hippocampal neurons which also contain dipeptide repeat proteins (DPR) formed from sense and antisense RAN (repeat associated non ATG-initiated) translation of the expanded repeat region itself. ‘Inappropriate’ formation, and aggregation, of DPR might therefore confer neurotoxicity and influence clinical phenotype. Consequently, we compared the topographic brain distribution of DPR in 8 patients with Frontotemporal dementia (FTD), 6 with FTD + MND and 7 with MND alone (all 21 patients bearing expansions in C9ORF72) using a polyclonal antibody to poly-GA, and related this to the extent of TDP-43 pathology in key regions of cerebral cortex and hippocampus. There were no significant differences in either the pattern or severity of brain distribution of DPR between FTD, FTD + MND and MND groups, nor was there any relationship between the distribution of DPR and TDP-43 pathologies in expansion bearers. Likewise, there were no significant differences in the extent of TDP-43 pathology between FTLD patients bearing an expansion in C9ORF72 and non-bearers of the expansion. There were no association between the extent of DPR pathology and TMEM106B or APOE genotypes. However, there was a negative correlation between the extent of DPR pathology and age at onset. Present findings therefore suggest that although the presence and topographic distribution of DPR may be of diagnostic relevance in patients bearing expansion in C9ORF72 this has no bearing on the determination of clinical phenotype. Because TDP-43 pathologies are similar in bearers and non-bearers of the expansion, the expansion may act as a major genetic risk factor for FTLD and MND by rendering the brain highly vulnerable to those very same factors which generate FTLD and MND in sporadic disease.Electronic supplementary materialThe online version of this article (doi:10.1186/2051-5960-2-70) contains supplementary material, which is available to authorized users.

Impact of ketamine on learning and memory function, neuronal apoptosis and its potential association with miR-214 and PTEN in adolescent rats.

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used as a general pediatric anesthetic and anti-depressive drug. Recent studies suggest that ketamine enhances neuronal apoptosis in developing rats. The goal of this study is to explore whether ketamine could result in learning and memory impairment and neurodegeneration in adolescent rats, and if so, whether the effects of ketamine are associated with miR-214 and PTEN expression. Fifty-day-old SD rats were randomly divided into three groups receiving ketamine at 30, or 80 mg/kg, i.p. or saline for seven consecutive days. Twenty-four hours after the last treatment, learning and memory function were tested by the Morris water maze. The rats were then decapitated, and the brains were isolated for detection of neuronal apoptosis and protein PTEN expression by TUNEL and immunohistochemistry respectively. Expression levels of the miR-214 and PTEN in the hippocampus were measured by qRT-PCR and western blot analysis respectively. Ketamine administered to the adolescent rats at a dose of 80 mg/kg rather than the lower dose of 30 mg/kg caused learning and memory impairment, increased the number of apoptotic cells in the hippocampal CA1 region, cerebral cortex and subcortical region, decreased the miR-214 levels and increased PTEN protein expression in hippocampus. The results suggest that ketamine at a dose of 80 mg/kg in the adolescent rats is able to induce the learning and memory impairment and neurodegeneration, in which the down-regulation of miR-214 and high expression of PTEN protein may be involved.

Ethanolic Extract of Astragali Radix and Salviae Radix Prohibits Oxidative Brain Injury by Psycho-Emotional Stress in Whisker Removal Rat Model

Myelophil, an ethanolic extract of Astragali Radix and Salviae Radix, has been clinically used to treat chronic fatigue and stress related disorders in South Korea. In this study, we investigated the protective effects of Myelophil on a whisker removal-induced psycho-emotional stress model. SD rats were subjected to whisker removal after oral administration of Myelophil or ascorbic acid for consecutive 4 days. Whisker removal considerably increased total reactive oxygen species in serum levels as well as cerebral cortex and hippocampal regions in brain tissues. Lipidperoxidation levels were also increased in the cerebral cortex, hippocampus regions, and brain tissue injuries as shown in histopathology and immunohistochemistry. However, Myelophil significantly ameliorated these alterations, and depletion of glutathione contents in both cerebral cortex and hippocampus regions respectively. Serum levels of corticosterone and adrenaline were notably altered after whisker removal stress, whereas these abnormalities were significantly normalized by pre-treatment with Myelophil. The NF-κB was notably activated in both cerebral cortex and hippocampus after whisker removal stress, while it was efficiently blocked by pre-treatment with Myelophil. Myelophil also significantly normalizes alterations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and interferon-γ in both gene expressions and protein levels. These results suggest that Myelophil has protective effects on brain damages in psycho-emotional stress, and the underlying mechanisms involve regulation of inflammatory proteins, especially NF-κB modulation.

Interconnection between brain and retinal neurodegenerations.

The eye is a special sensory organ, which is basically an extension of the brain. Both are derived from neural tube and consist of neurons. Therefore, diseases of both the brain and eye should have some similarity. Neurodegenerative disorders like Alzheimer's disease (AD) is the major cause of dementia in the world. Amyloid deposition in the cerebral cortex and hippocampal region is the basic pathology in AD. But along with it, there are various changes that take place in the eye, i.e., abnormal pupillary reaction, decreased vision, decreased contrast sensitivity, visual field changes, loss of retinal ganglionic cells and retinal fiber layer, peripapillary atrophy, increased cup-disk ratio, retinal thinning, tortuosity of blood vessels, and deposition of Aβ-like substance in the retina. And these changes are present in the early part of the disease when only mild cognitive impairment is there. As the brain is covered by a hard bony skull which makes it difficult to directly visualize the changes occurring in the brain at molecular levels, finer details of disease progression are not available with us. But the eye is the window of the brain; with advanced modern techniques, we can directly visualize the changes in the retina at a very fine level. Therefore, by depicting neurodegenerative changes in the eye, we can diagnose and manage AD at very early stages. Along with it, retinal neurodegenerations like glaucoma and age-related macular degeneration (ARMD) are the major cause of loss of vision, and still, there are no effective treatment modalities for these blinding conditions. So if we can understand its pathogenesis and progression by correlating with brain neurodegenerations, we can come up with a better therapy for glaucoma and ARMD.

Cortical innervation of the hypoglossal nucleus in the non-human primate (Macaca mulatta).

The corticobulbar projection to the hypoglossal nucleus was studied from the frontal, parietal, cingulate, and insular cortices in the rhesus monkey by using high-resolution anterograde tracers and stereology. The hypoglossal nucleus received bilateral input from the face/head region of the primary (M1), ventrolateral pre- (LPMCv), supplementary (M2), rostral cingulate (M3), and caudal cingulate (M4) motor cortices. Additional bilateral corticohypoglossal projections were found from the dorsolateral premotor cortex (LPMCd), ventrolateral proisocortical motor area (ProM), ventrolateral primary somatosensory cortex (S1), rostral insula, and pregenual region of the anterior cingulate gyrus (areas 24/32). Dense terminal projections arose from the ventral region of M1, and moderate projections from LPMCv and rostral part of M2, with considerably fewer hypoglossal projections arising from the other cortical regions. These findings demonstrate that extensive regions of the non-human primate cerebral cortex innervate the hypoglossal nucleus. The widespread and bilateral nature of this corticobulbar connection suggests recovery of tongue movement after cortical injury that compromises a subset of these areas, may occur from spared corticohypoglossal projection areas located on the lateral, as well as medial surfaces of both hemispheres. Since functional imaging studies have shown that homologous cortical areas are activated in humans during tongue movement tasks, these corticobulbar projections may exist in the human brain.

Do Astrocytes Collaborate with Neurons in Spreading the “Infectious” Aβ and Tau Drivers of Alzheimer’s Disease?

Evidence has begun emerging for the “contagious” and destructive Aβ42 (amyloid-beta42) oligomers and phosphorylated Tau oligomers as drivers of sporadic Alzheimer’s disease (AD), which advances along a pathway starting from the brainstem or entorhinal cortex and leading to cognition-related upper cerebral cortex regions. Seemingly, Aβ42 oligomers trigger the events generating the neurotoxic Tau oligomers, which may even by themselves spread the characteristic AD neuropathology. It has been assumed that only neurons make and spread these toxic drivers, whereas their associated astrocytes are just janitorial bystanders/scavengers. But this view is likely to radically change since normal human astrocytes freshly isolated from adult cerebral cortex can be induced by exogenous Aβ25-35, an Aβ42 proxy, to make and secrete increased amounts of endogenous Aβ42. Thus, it would seem that the steady slow progression of AD neuropathology along specific cognition-relevant brain networks is driven by both Aβ42 and phosphorylated Tau oligomers that are variously released from increasing numbers of “contagion-stricken” members of tightly coupled neuron–astrocyte teams. Hence, we surmise that stopping the oversecretion and spread of the two kinds of “contagious” oligomers by such team members, perhaps via a specific CaSR (Ca2+-sensing receptor) antagonist like NPS 2143, might effectively treat AD.

Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes

BackgroundRecent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic effects. In the present study, we intend to study the efficacy of antidotes comprising of HI-6 (1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]-methyl]-2-[(hydroxyimino) methyl] pyridinium dichloride), atropine and midazolam on soman induced neurodegeneration and the expression of c-Fos, Calpain, and Bax levels in discrete rat brain areas.ResultsTherapeutic regime consisting of HI-6 (50 mg/kg, i.m), atropine (10 mg/kg, i.m) and midazolam (5 mg/kg, i.m) protected animals against soman (2 × LD50, s.c) lethality completely at 2 h and 80% at 24 h. HI-6 treatment reactivated soman inhibited plasma and RBC cholinesterase up to 40%. Fluoro-Jade B (FJ-B) staining of neurodegenerative neurons showed that soman induced significant necrotic neuronal cell death, which was reduced by this antidotal treatment. Soman increased the expression of neuronal proteins including c-Fos, Bax and Calpain levels in the hippocampus, cerebral cortex and cerebellum regions of the brain. This therapeutic regime also reduced the soman induced Bax, Calpain expression levels to near control levels in the different brain regions studied, except a mild induction of c-Fos expression in the hippocampus.ConclusionRats that received antidotal treatment after soman exposure were protected from mortality and showed reduction in the soman induced expression of c-Fos, Bax and Calpain and necrosis. Results highlight the need for timely administration of better antidotes than standard therapy in order to prevent the molecular and biochemical changes and subsequent long term neurological effects induced by nerve agents.

Localization of heat shock proteins in cerebral cortical cultures following induction by celastrol

Hsp70, Hsp32, and Hsp27 were induced by celastrol in rat cerebral cortical cultures at dosages that did not affect cell viability. Pronounced differences were observed in the cellular localization of these heat shock proteins in cell types of cerebral cortical cultures. Celastrol-induced Hsp70 localized to the cell body and cellular processes of neurons that were identified by neuron-specific βIII-tubulin. Hsp70 was not detected in adjacent GFAP-positive glial cells that demonstrated a strong signal for Hsp27 and Hsp32 in both glial cell bodies and cellular processes. Cells in the cerebral cortex region of the brain are selectively impacted during the progression of Alzheimer's disease which is a "protein misfolding disorder." Heat shock proteins provide a line of defense against misfolded, aggregation-prone proteins. Celastrol is a potential agent to counter this neurodegenerative disorder as recent evidence indicates that in vivo administration of celastrol in a transgenic model of Alzheimer's reduces an important neuropathological hallmark of this disease, namely, amyloid beta pathology that involves protein aggregation.

Eustress humor associated laughter compared to stress differentially modulates EEG power spectral density across frequency bins 1‐40Hz (684.10)

Eustress and distress are complex processes that can differentially modulate positive or negative aspects of psychoneuroimmunological (PNI) mechanisms. The eustress of humor associated mirthful laughter (HAML) relate to fundamental aspects of human behavior. Some experiences are characterized by modulating PNI mechanisms and behavior for positive health benefits. No known electroencephalographic (EEG) study has been conducted to differentiate Power Spectral Density µV2 (PSD) correlates across EEG frequency bins1‐40Hz for comparison of eustress HAML and distress. Purpose: This study assessed EEG PSD in 31 university students during HAML and distress. Methods: In a cross‐over design each subject was randomly administered two 10 minute videos: HAML (America's Funniest Home Videos) and Stress (Movie ‐ Saving Private Ryan). EEG wave band activity was recorded from 9 scalp locations F3, Fz, F4, C3, Cz, C4, P3, POz, and P4 using the EEG B‐Alert 10X System™. Results: HAML compared to distress showed Beta Band Activity (13‐30Hz) (βBA) (p=0.01) and Gamma Band Activity (γBA) (31‐40HZ) (p=0.001) for PSD greatest for all 9 regions. Most profound was HAML γBA was significantly greater than HAML βBA (p=0.01) for the same 9 regions. θBA (3‐7Hz) and αBA (8‐12Hz) for P3 vs P4 showed HAML greater PSD in the P3 region than P4 (p&lt;0.01). Frontal region γBA and βBA was different from θBA and αBA for HAML p&lt; .05. Central βBA and γBA, distress was different from HAML, p&lt;.0001. Parietal αBA, βBA and γBA, distress was different from HAML (p&lt;0.05). Conclusions: HAML shows EEG PSD correlates of change for specific bandwidths but greatest for γBA across all measured cerebral cortex regions (synchrony). Previous research show spectral density γBA is suitable for EEG‐based emotion classification of happiness and sadness. Our EEG findings further suggest eustress HAML can increase PSD of γBA synchrony and thus potentially enhance cognition, sensory perception, memory/recall, happiness &amp; other health benefits.

Attributing awareness to oneself and to others

This study tested the possible relationship between reported visual awareness ("I see a visual stimulus in front of me") and the social attribution of awareness to someone else ("That person is aware of an object next to him"). Subjects were tested in two steps. First, in an fMRI experiment, subjects were asked to attribute states of awareness to a cartoon face. Activity associated with this task was found bilaterally within the temporoparietal junction (TPJ) among other areas. Second, the TPJ was transiently disrupted using single-pulse transcranial magnetic stimulation (TMS). When the TMS was targeted to the same cortical sites that had become active during the social attribution task, the subjects showed symptoms of visual neglect in that their detection of visual stimuli was significantly affected. In control trials, when TMS was targeted to nearby cortical sites that had not become active during the social attribution task, no significant effect on visual detection was found. These results suggest that there may be at least some partial overlap in brain mechanisms that participate in the social attribution of sensory awareness to other people and in attributing sensory awareness to oneself.

Panax quinquefolium involves nitric oxide pathway in olfactory bulbectomy rat model

Olfactory bulbectomy (OBX) is a well known screening model for depression. Panax quinquefolium (PQ) is known for its therapeutic potential against several psychiatric disorders. Nitric oxide (NO), an intercellular messenger has been suggested to play a crucial role in the pathogenesis of depression. The present study was designed to explore the possible involvement of NO mechanism in the protective effect of PQ against olfactory bulbectomy induced depression. Wistar rats were bulbectomized surgically and kept for a rehabilitation period of two weeks. PQ (50, 100 and 200mg/kg; p.o.) alone and in combination with NO modulators like l-NAME (10mg/kg, i.p.) and l-arginine (100mg/kg; i.p.) were then administered daily for another two weeks. Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in forced swim test, hyperactivity in open field arena, and anhedonic like response in sucrose preference test. Further, OBX caused elevation in serum corticosterone levels and increased oxidative–nitrosative damage. These deficits were integrated with increased levels of neuroinflammatory cytokines (TNF-α), apoptotic factor (caspase-3) and a marked reduction in neurogenesis factor (BDNF) in both cerebral cortex and hippocampal regions of bulbectomized rats. Treatment with PQ significantly and dose-dependently restored these behavioral, biochemical and molecular alterations associated with OBX. Further, pretreatment of l-NAME with subeffective dose of PQ (100mg/kg) significantly potentiated its protective effects; however l-arginine pretreatment reversed the beneficial effects. The present study suggests that protective effect of P. quinquefolium might involve nitric oxide modulatory pathway against olfactory bulbectomy-induced depression in rats.

Neuroprotection of posttreatment with risperidone, an atypical antipsychotic drug, in rat and gerbil models of ischemic stroke and the maintenance of antioxidants in a gerbil model of ischemic stroke

Risperidone, an atypical antipsychotic drug, has been discovered to have some beneficial effects beyond its original effectiveness. The present study examines the neuroprotective effects of risperidone against ischemic damage in the rat and gerbil induced by transient focal and global cerebral ischemia, respectively. The results showed that pre- and posttreatment with 4 mg/kg risperidone significantly protected against neuronal death from ischemic injury. Many NeuN-immunoreactive neurons and a few F-J B-positive cells were found in the rat cerebral cortex and gerbil hippocampal CA1 region (CA1) in the risperidone-treated ischemia groups compared with those in the vehicle-treated ischemia group. In addition, treatment with risperidone markedly attenuated the activation of microglia in the gerbil CA1. On the other hand, we found that treatment with risperidone significantly maintained the antioxidants levels in the ischemic gerbil CA1. Immunoreactivities of superoxide dismutases 1 and 2, catalase, and glutathione peroxidase were maintained in the stratum pyramidale of the CA1; the antioxidants were very different from those in the vehicle-treated ischemia groups. In brief, our present findings indicate that posttreatment as well as pretreatment with risperidone can protect neurons in the rat cerebral cortex and gerbils CA1 from transient cerebral ischemic injury and that the neuroprotective effect of risperidone may be related to attenuation of microglial activation as well as maintenance of antioxidants.