Neuropathology and behavioral impairments after three types of global ischemia surgery in Meriones unguiculatus: Evidence in motor cortex, hippocampal CA1 region and the neostriatum

The effects of three types of global ischemia by occlusion of carotid artery on motor and exploratory behaviors of Gerbils were evaluated by the Activity Cage and Rota rod tests. Animals were divided based on two surgical criteria: unilateral (UNI) or bilateral (BIL) carotid occlusion, with (REP) or without (OCL) reperfusion; and their behavior was evaluated on the fourth (4) or sixth (6) day. There was reduction of cell number in striatum, motor cortex M1 area, and hippocampal CA1 area in all groups in comparison to control animals. For M1 area and striatum, the largest reduction was observed in UNI6, UNI4, and BIL4 groups. Neuronal loss was also observed in CA1 area of BIL4 rodents. There was a decrease in crossings and rearings in all groups in activity cage test, compared to control. Reperfusion, unilateral and bilateral occlusion groups showed decrease in crossings. Only the BIL4 showed a decrease of rearing. In the Rota rod test, except the UNIOCL6, the groups showed a decrease in the balance in comparison to control. Both groups with REP4 showed a major decrease in balance. These findings suggest that both unilateral and bilateral carotid occlusions with reperfusion produce impairments of motor and exploratory behavior. (C) 2011 Elsevier B.V. All rights reserved.

Changes in hippocampal gene expression by 7-nitroindazole in rats submitted to forced swimming stress

Nitric oxide (NO) is an atypical neurotransmitter that has been related to the pathophysiology of major depression disorder. Increased plasma NO levels have been reported in depressed and suicidal patients. Inhibition of neuronial nitric oxide synthase (nNOS), on the other hand, induces antidepressant effects in clinical and pre-clinical trials. The mechanisms responsible for the antidepressant-like effects of nNOS inhibitors, however, are not completely understood. In this study, genomic and proteomic analyses were used to investigate the effects of the preferential nNOS inhibitor 7-nitroindazole (7-NI) on changes in global gene and protein expression in the hippocampus of rats submitted to forced swimming test (FST). Chronic treatment (14 days, i.p.) with imipramine (15 mg/kg daily) or 7-NI (60 mg/kg daily) significantly reduced immobility in the FST. Saturation curves for Serial analysis of gene expression libraries showed that the hippocampus of animals submitted to FST presented a lower number of expressed genes compared to non-FST stressed groups. Imipramine, but not 7-NI, reverted this effect. GeneGo analyses revealed that genes related to oxidative phosphorylation, apoptosis and survival controlled by HTR1A signaling and cytoskeleton remodeling controlled by Rho GTPases were significantly changed by FST. 7-NI prevented this effect. In addition, 7-NI treatment changed the expression of genes related to transcription in the cAMP response element-binding pathway. Therefore, this study suggests that changes in oxidative stress and neuroplastic processes could be involved in the antidepressant-like effects induced by nNOS inhibition.

Novelty, but Not Operant Aversive Learning, Enhances Fos and Egr-1 Expression in the Medial Prefrontal Cortex and Hippocampal Areas of Rats

Immediate early genes (IEG) are presumed to be activated in response to stress, novelty, and learning. Evidence supports the involvement of prefrontal and hippocampal areas in stress and learning, but also in the detection of novel events. This study examined whether a previous experience with shocks changes the pattern of Fos and Egr-1 expression in the medial prefrontal cortex (mPFC), the hippocampal cornus ammonis 1 (CA1), and dentate gyrus (DG) of adult male Wistar rats that learned to escape in an operant aversive test. Subjects previously exposed to inescapable footshocks that learned to escape from Shocks were assigned to the treated group (EXP). Subjects from Group Novelty (NOV) rested undisturbed during treatment and also learned to escape in the test. The nonshock group (NSH) rested undisturbed in both sessions. Standard immunohistochemistry procedures were used to detect the proteins in brain sections. The results show that a previous experience with shocks changed the pattern of IEG expression, then demonstrating c-fos and egr-1 induction as experience-dependent events. Compared with NSH and EXP an enhanced Fos expression was detected in the mPFC and CA1 subfield of Group NOV, which also exhibited increased Egr-1 expression in the mPFC and DG in comparison to NSH. No differences were found in the DG for Fos, or in the CA1 for Egr-1. Novelty, and not the operant aversive escape learning, seems to have generated IEG induction. The results suggest novel stimuli as a possible confounding factor in studies on Fos and/or Egr-1 expression in aversive conditions.

On the relationship between neurocysticercosis and mesial temporal lobe epilepsy associated with hippocampal sclerosis: coincidence or a pathogenic relationship?

Neurocysticercosis (NCC) and mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) are two common worldwide forms of focal epilepsy. In regions where NCC is endemic, both diseases can be observed in the same patient. There is recent and growing evidence suggesting that NCC might contribute to or even cause MTLE-HS. In this article, we review the literature regarding NCC and temporal lobe epilepsy, specifically addressing the relationship between NCC and MTLE-HS. In addition, we review some scenarios where NCC seems to emerge as a causative agent or contributor to the development of MTLE-HS in some patients. This association is important because it may have an impact on the evaluation and treatment of a sizable proportion of patients with epilepsy. Insights from these clinical observations might also contribute to the understanding of the neurobiology of both NCC and MTLE-HS. We hope that our review might shed some light on this interesting interplay between two of the most common worldwide conditions associated with human focal epilepsy.

Slice: experiência de gestão de um processo de projeto paramétrico, com superfícies complexas

O artigo apresenta uma reflexão sobre a gestão do processo de projeto paramétrico, com superfícies complexas, baseado em duas experiências realizadas no Instituto de Arquitetura e Urbanismo, da USP de São Carlos, pelo grupo de pesquisa Nomads.usp. SLICE é o resultado parcial de um pavilhão temporário, com superfícies complexas, desenvolvido por meio de projeto paramétrico e técnicas de fabricação digital. Utilizou-se o procedimento de uma pesquisa-ação2 com alunos de graduação e recém-formados em arquitetura, arquitetos do Nomads.usp e a indústria. Os experimentos apontaram para reflexões sobre algumas mudanças na gestão destes processos, para facilitar a viabilidade técnico-construtiva e gerar conhecimento nas áreas de projeto paramétrico, fabricação digital e gestão. O artigo tem caráter exploratório e o desafio é entender e avaliar a gestão do projeto paramétrico em relação a restrição de material, custo de execução e tempo de produção.

Different levels of MT-I/II between patients with MTLE with or without seizure generalization: does hippocampal MT-I/II affects seizure spread, or does seizure spread promotes differential expression of MT-I/II?

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) were evaluated for expression of MT-I/II and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis and reduced neuronal population. MT-I/II levels did not correlate with any clinical variables, but patients with secondary generalized seizures (SGS) had less MT-I/II than patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from MTLE patients and our data suggest that it may be associated with different seizure spread patterns.

Spectral characteristics of the hippocampal LFP during contextual fear conditioning

OBJECTIVE: The hippocampus has an important role in the acquisition and recall of aversive memories. The objective of this study was to investigate the relationship among hippocampal rhythms. METHODS: Microeletrodes arrays were implanted in the hippocampus of Wistar rats. The animals were trained and tested in a contextual fear conditioning task. The training consisted in applying shocks in the legs. The memory test was performed 1 day (recent memory) or 18 days (remote memory) after training. We proposed a measure based on the FFT power spectrum, denominated "delta-theta ratio", to characterize the different behaviors (active exploration and freezing) and the memories types. RESULTS: The delta-theta ratio was able to distinguish recent and remote memories. In this study, the ratio for the 18-day group was smaller than for the 1-day group. Moreover, this measure was useful to distinguish the different behavior states active exploration and freezing. CONCLUSIONS: The results suggest delta-theta oscillations could reflect the demands on information processing during recent and remote memory recalls.

Chronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis

Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. In unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. In stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. In stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis.

Enhancement of behavioral sensitization, anxiety-like behavior, and hippocampal and frontal cortical CREB levels following cocaine abstinence in mice exposed to cocaine during adolescence

Adolescence has been linked to greater risk-taking and novelty-seeking behavior and a higher prevalence of drug abuse and risk of relapse. Decreases in cyclic adenosine monophosphate response element binding protein (CREB) and phosphorylated CREB (pCREB) have been reported after repeated cocaine administration in animal models. We compared the behavioral effects of cocaine and abstinence in adolescent and adult mice and investigated possible age-related differences in CREB and pCREB levels. Adolescent and adult male Swiss mice received one daily injection of saline or cocaine (10 mg/kg, i.p.) for 8 days. On day 9, the mice received a saline injection to evaluate possible environmental conditioning. After 9 days of withdrawal, the mice were tested in the elevated plus maze to evaluate anxiety-like behavior. Twelve days after the last saline/cocaine injection, the mice received a challenge injection of either cocaine or saline, and locomotor activity was assessed. One hour after the last injection, the brains were extracted, and CREB and pCREB levels were evaluated using Western blot in the prefrontal cortex (PFC) and hippocampus. The cocaine-pretreated mice during adolescence exhibited a greater magnitude of the expression of behavioral sensitization and greater cocaine withdrawal-induced anxiety-like behavior compared with the control group. Significant increases in CREB levels in the PFC and hippocampus and pCREB in the hippocampus were observed in cocaine-abstinent animals compared with the animals treated with cocaine in adulthood. Interestingly, significant negative correlations were observed between cocaine sensitization and CREB levels in both regions. These results suggest that the behavioral and neurochemical consequences of psychoactive substances in a still-developing nervous system can be more severe than in an already mature nervous system