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Background The hippocampus is a brain structure important for memory and cognitive function. Physical activity may help prevent hippocampal atrophy. However, few studies have measured sedentary behavior (SB) and intensity-specific physical activity using an accelerometer. This study aimed to examine the cross-sectional associations of objectively-determined SB, light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) measured by an accelerometer with hippocampal volume among community-dwelling older adults using compositional data analysis (CoDa) approach. Methods This cross-sectional study was part of the Neuron to Environmental Impact across Generations (NEIGE) study. A randomly recruited sample of 485 Japanese older adults (47% male; aged 65-84 years) wore tri-axial accelerometers (Omron Healthcare) for seven consecutive days in 2017. Hippocampal volume was measured with magnetic resonance imaging and the left and right hippocampal volumes were automatically segmented using FreeSurfer software. Associations of sedentary and physically active behaviors with hippocampal volume were examined with compositional linear regression analysis based on isometric log-ratio transformations of time use adjusted for potential confounding factors. Results The relative proportion of time spent in MVPA, compared to the other two activities, was significantly positively associated with right hippocampal volume (β: 57.1, p-value = 0.027).However, no association existed between higher proportions of MVPA and left hippocampal volume, or between proportions of SB or LPA with either left or right hippocampal volumes. Conclusions The proportion of time spent in MVPA, relative to the other two activities, was significantly positively associated with right hippocampal volume. MVPA may be beneficial for maintaining hippocampal volume.

The current study aimed to evaluate the effects of exercise on negative and cognitive symptoms and simultaneous evaluation of brain and hippocampus volume in patients with schizophrenia. Forty patients with schizophrenia were randomly divided into two groups. The intervention group, in addition to pharmacological treatment, underwent a multi-session exercise program for 8 weeks. At the beginning and end of the study, patients were assessed for cognitive status and negative symptoms using the Mini-Mental State Examination (MMSE) and Positive and Negative Syndrome Scale (PANSS), respectively. Total brain volume and hippocampus volume were also measured using magnetic resonance imaging. Overall, mean MMSE score significantly improved over time, but this improvement was greater in the intervention group (29%) compared to the control group (11%). The same was true for the PANSS negative score (21.5% vs. 53.5%). Absolute hippocampus volume during these 8 weeks, in exercise and control groups, increased from 6.24 to 7.11 and 6.44 to 6.59, respectively. The greater increase in volume obtained in the intervention group was statistically significant ( p = 0.003). Exercise may be associated with improved cognitive function and negative symptoms in patients with schizophrenia; however, additional studies are warranted. [ Journal of Psychosocial Nursing and Mental Health Services, 60 (5), 37–43.]

Icariin (ICA) has a significant capacity to protect against depression and hippocampal injury, but it cannot effectively cross the blood-brain barrier and accumulate in the brain. Therefore, the mechanism by which ICA protects against hippocampal injury in depression remains unclear. In this study, we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression. A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks, after which 120 mg/kg ICA was administered subcutaneously every day. The results showed that ICA alleviated depressive symptoms, learning and memory dysfunction, dysfunctional neurogenesis, and neuronal loss in the dentate gyrus of rats with depression. Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone. The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation. Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid. These proteins were mainly involved in the ribosome, PI3K-Akt signaling, and interleukin-17 signaling pathways. Parallel reaction monitoring mass spectrometry showed that Rps4x, Rps12, Rps14, Rps19, Hsp90b1, and Hsp90aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA. In contrast, HtrA1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA. These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid. The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.

Background The relationship between depression and adaptive immunity has gradually attracted increasing attentions. However, no consistent conclusions have been drawn about alterations in adaptive immunity in depression. Methods Eight-week-old weight-matched male C57BL/6 mice were randomly divided into a chronic unpredictable mild stress (CUMS) model group and a control group, with twelve mice in each group. After 8-week CUMS modeling duration and depressive behavioral tests, T cell responses were evaluated at the cell, cytokine, and cell-specific transcription factor levels. Lymphocytes in the spleen were detected by flow cytometry; serum cytokines were assessed by enzyme-linked immunosorbent assays; expression levels of cytokines and cell-specific transcription factors in the hippocampus were determined by quantitative PCR. Results CUMS exposure induced depression-like behaviors with decreased sucrose preference and longer immobility time in the tail suspension test and forced swim test. The CUMS group had a lower proportion of CD4+ T cells than the control group. A decreased number of T helper 17 (Th17) cells in the spleen and down regulated serum interleukin (IL)-17 and hippocampal retinoid-related orphan receptor-γt levels were detected in the CUMS group. Depressed mice in the CUMS group showed increases in serum IL-1β and IL-6 and hippocampal IL-6 and IL-4 levels. Limitation The study was based on a mouse model. Further studies are needed to determine whether the results are applicable to patients with depression. Conclusion CUMS exposure can induce depression-like behaviors and decrease Th17 cell counts.

Objectives The present study aimed to investigate the effects of acute hypoxia exposure following prenatal stress on the novelty-seeking behavior and hippocampus of adolescent rats. Methods The offspring were divided into prenatal stress (PS) and non-stress (NS) groups. Both groups were exposed to hypoxia on postnatal day 10 (P10) while control groups were undisturbed. Novel object recognition task was performed in each group. Next, brains were collected to examine hippocampus via immunohistochemical and biochemical studies on postnatal day 35 (P35). Results PS decreased novelty discrimination and synaptophysin (SYN) expressions in both CA1 and CA3 of the hypoxia group prominently (p < 0.05). Nestin-expressing cells were reduced while vascular endothelial growth factor (VEGF) expression was enhanced in the subgranular zone (SGZ) of PS-hypoxia group (p < 0.05). VEGF enhancement triggered angiogenesis in the CA1 and CA3 significantly (p < 0.05). PS also increased thiobarbituric acid reactive substances (TBARS) levels in the hypoxia group as a result of oxidative stress (p < 0.05). Conclusion These findings demonstrated that PS exacerbates neurodevelopmental deficits in the hippocampus of acute hypoxia-induced offspring in adolescence., Ege University [18-SBE-004/2018], Ege University, Grant/Award Number: 18-SBE-004/2018

This study aimed to investigate the relationship between different patterns of molar crown loss and the association between symmetrical and asymmetrical shortening molar teeth with memory impairment. Male Wistar rats were divided into four groups (n=10) including control, SLM (shortened left molar), SRM (shortened right molar), and SBM (shortened bilateral molar) groups. Morris water maze (MWM) and passive avoidance test (PAT) were performed to assess spatial and fear memory, respectively. Besides, histological assessment of hippocampus and gingival tissues was done. In the MWM test, SBM and SLM groups had higher escape latency over training trials and spent less time in the target quadrant in the probe trial (P < 0.01). In the PAT, step-through latency was significantly reduced in three groups, and time spent in the dark compartment increased in SBM (P < 0.01) and SLM (P < 0.05) groups. In addition, each teeth shortening group indicated a reduction in density (P < 0.01) and thickness layer (P < 0.05) of pyramidal cells. Gingival was normal after shortening of the molar crown. Different patterns of molar teeth shortening induced learning and memory impairment, however, symmetrical molar teeth shortening has more effects on memory impairment.

The phytogenic flavanol component of the plant Rhusverniciflua Stokes is fustin which is implicated in various disease aliments and has promising therapeutic efficacy and a long history of its uses in the Indian medicinal system. The present study investigated the ameliorative effect of fustin in streptozotocin (STZ) induced cognitive impairments in the diabetic animal paradigm. A total of five different animal groups were used for the present study.The preclinical efficacy of fustin at 50 mg/kg and 100 mg/kg was studied in diabetic male rats by employing a 35-day study design. In the present investigation the Morris water maze test (MWM) and elevated plus maze (EPM) test were employed as behavioral paradigms for the assessment of memory impairments. The study design also carried out certain biochemical parameters which include glutathione (GSH), superoxide dismutase (SOD), catalase activity (CAT), malondialdehyde (MDA), nitric oxide (NO), relative interleukin-6 (IL-6), and IL-1B in samples obtained from cerebral cortex and hippocampus. The behavioral parameters with MWM and EPM were significant restored in fustin treatment groups as compared to elevated levels in the diabetic control group. Furthermore, fustin significantly improved the altered levels of several biochemical parameters for cognitive dysfunction such as GSH, SOD, CAT, MDA, NO, and relative IL-6 and IL-1B compared to a diabetic control group. The present investigation highlights certain preclinical pieces of evidence that strongly indicate that fustin might restore the normal cognitive function in the experimental animal paradigm.

Objective To assess whether hippocampal spindles and barques are markers of epileptogenicity. Methods Focal epilepsy patients that underwent stereo-electroencephalography implantation with at least one electrode in their hippocampus were selected (n = 75). The occurrence of spindles and barques in the hippocampus was evaluated in each patient. We created pairs of pathologic and pathology-free groups according to two sets of criteria: 1. Non-invasive diagnostic criteria (patients grouped according to focal epilepsy classification). 2. Intracranial neurophysiological criteria (patient’s hippocampi grouped according to their seizure onset involvement). Results Hippocampal spindles and barques appear equally often in both pathologic and pathology-free groups, both for non-invasive (Pspindles = 0.73; Pbarques = 0.46) and intracranial criteria (Pspindles = 0.08; Pbarques = 0.26). In Engel Class I patients, spindles occurred with similar incidence both within the non-invasive (P = 0.67) and the intracranial criteria group (P = 0.20). Barques were significantly more frequent in extra-temporal lobe epilepsy defined by either non-invasive (P = 0.01) or intracranial (P = 0.01) criteria. Conclusions Both spindles and barques are normal entities of the hippocampal intracranial electroencephalogram. The presence of barques may also signify lack of epileptogenic properties in the hippocampus. Significance Understanding that hippocampal spindles and barques do not reflect epileptogenicity is critical for correct interpretation of epilepsy surgery evaluations and appropriate surgical treatment selection.

Status epilepticus (SE) is a neurological emergency, and delayed management can lead to higher morbidity and mortality. It is thought that prolonged seizures stimulate stem cells in the hippocampus and that epileptogenesis may arise from aberrant connections formed by newly born cells, while others have suggested that the acute neuroinflammation and gliosis often seen in epileptic hippocampi contribute to hyperexcitability and epilepsy development. Previous studies have identified the expression of homeodomain-only protein (HOP) in the hippocampal dentate gyrus (HDG) and the heart. HOP was found to be a regulator of cell proliferation and differentiation during heart development, while it maintains the ‘heart conduction system’ in adulthood. However, little is known about HOP function in the adult HDG, particularly in the SE setting. Here, a HOP immunohistochemical profile in an SE mouse model was established. A total of 24 adult mice were analyzed 3–10 days following the SE episode, the ‘acute phase’. Our findings demonstrate a significant downregulation of HOP and BLBP protein expression in the SE group following SE episodes, while HOP/Ki67 coexpression did not remarkably differ. Furthermore, coexpression of HOP/S100β and HOP/Prox1 was not observed, although we noticed insignificant HOP/DCX coexpression level. The findings of this study show no compelling evidence of proliferation, and newly added neurons were not identified during the acute phase following SE, although HOP protein expression was significantly decreased in the HDG. Similar to its counterpart in the adult heart, this suggests that HOP seems to play a key role in regulating signal conduction in adult hippocampus. Moreover, acute changes in HOP expression following SE could be part of an inflammatory response that could subsequently influence epileptogenicity., Highlights • Homeodomain-only protein (HOP) is exclusively expressed in adult hippocampal dentate gyrus. • In adult HDG, HOP-expressing cells could represent a unique terminally-differentiated, highly specialized glial subtype. • . A single episode of status epilepticus (SE) does not affect cell proliferation nor differentiation in adult HDG. • HOP protein is downregulated following SE and could influence epileptogenicity. • Similar to its function in adult heart, HOP seems to play critical role in regulating adult ‘hippocampus conduction system’. • HOP protein could represent a molecular target for acute management of SE to minimize its cumulative effects.

To investigate the protective effects of metformin on the diabetic mice with cognitive impairment induced by the combination of streptozotocin (STZ) and isoflurane anesthesia. The isoflurane-anesthetized cognitive impairment model mice were established and then observed via behavioral tests and histopathological examination. Then these model mice were randomly assigned to three groups, which received the PBS, low and high doses of metformin, respectively. The body weight, food and water consumption of model mice were measured every other day. The mechanisms of metformin on ameliorating the cognitive dysfunction were further investigated by histomorphological, biochemical and Western blot analysis. After 14-days treatment of metformin, the diabetic symptoms in STZ-induced diabetic mice were significantly alleviated. Metformin could restore the isoflurane- and STZ-induced hippocampal tissue damage, cognitive and memory impairment in exposed space via improving the oxidative stress, upregulating the contents of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in the hippocampus tissues of diabetic mice. Furthermore, chronic treatment of metformin significantly down-regulated the expression of AGEs, RAGE, pNF-κB, iNOS, and COX-2. In conclusion, metformin can improve the isoflurane- and STZ-induced cognitive impairment in diabetic mice via improving oxidative stress and inhibiting the AGEs/RAGE/NF-κB signaling pathway.

The aim of this study was to evaluate the effects of transcranial direct current stimulation (tDCS) on anxiety-like behavior and neural parameters in rats with chronic pain exposed to alcohol. Thirty-six adult male Wistar rats were randomly assigned to control (CT), neuropathic pain (NP), NPtDCS, NP + alcohol (NPAL), or NPALtDCS groups, subjected to sciatic nerve chronic constriction injury (CCI) and exposed to alcohol (20% v/v solution, 4 g/kg) or vehicle by gavage for 15 days. Afterward, rats were treated using bimodal tDCS (0.5 mA/20 min/8 days) and tested in the open field. Rats were killed 24 h after the last behavioral assessment, and brain and spinal cord tissue samples were collected and processed for NPY immunohistochemistry, expression of Il1a and Il1b in the spinal cord, cerebellum, and hippocampus, and levels of IL-1α and IL-1β in the same brain structures and the striatum. tDCS reverted the anxiety-like behavior induced by CCI and alcohol, and the increased expression of Il1a in the spinal cord induced by alcohol, which increased the expression of Il1b in the cerebellum. In addition, tDCS modulated the hypothalamic NPY-immunoreactivity, increased the levels of IL-1α in the hippocampus (like NP and AL), and increased the expression of Il1b in the spinal cord (like AL). Thus, this study shows that tDCS changes NP and alcohol-induced anxiety-like behavior, possibly through its central modulatory effect of NPY and spinal cord expression of Il1a and Il1b, being considered a treatment option for alcohol and NP-induced anxiety symptoms.

Introduction: Amyloid plaques in the brain increase with age. Thus, the present study aimed to evaluate the effect of continuous and interval training on Amyloid β 42 (Aβ42) and Malondialdehyde (MDA) levels in hippocampus of elderly rats. Methods: The present study was experimental one with two experimental groups and one control group. Thirty old male Wistar rats (18 weeks-old) divided into 3 groups, including interval training, continuous training, and control. Continuous training was performed for 8 weeks with 65 to 70% VO2max and interval training was performed for 8 weeks with 5-8 repetitions of 2 minutes of working with 80-100% VO2max and 2 minutes active rest with 50% of VO2max for 8 weeks. Hippocampal samples were extracted 48 hours after the last training session to measure protein levels of Aβ42 and MDA. One-way ANOVA and Tukey post hoc test was used for data analysis. Results: Hippocampus Aβ42 levels in continuous training groups were significantly lower than the control group (P=0.001). In addition, Aβ42 levels in hippocampus of interval training groups were significantly lower than the control group (P=0.001). However, no significant differences were found in Aβ42 levels between continuous and interval training groups (p=0.502). MDA levels in continuous training groups were significantly lower than the control group (P=0.016). In addition, MDA levels in interval training groups were significantly lower than the control group (P=0.046) But no significant differences were found in hippocampal MDA protein levels between continuous and interval training groups (p=866). Conclusion: Continuous and interval training through decreasing oxidative stress, decrease Aβ42 levels in the hippocampus of the elderly rat, thus probably continuous and interval training can prevent neurodegenerative disease caused by aging through modulating oxidative stress and Aβ42.

The aim of the study was to investigate the influence of chitosan oligosaccharide (COS) on some antioxidant and cytokine levels in the rat hippocampus as well as synaptophysin (SYP) immunoreactivity in the cerebral cortex of the cadmium (Cd) exposed rats. Thirty-two male albino Wistar rats were divided randomly into four equal groups as control (C; n = 8), Cd (n = 8), COS (n = 8), and Cd + COS (CdCOS; n = 8). The rats in the Cd and CdCOS groups received Cd chloride (CdCl2) (2 mg/kg/d) orally by gastric gavage three times a week for 4 weeks. Besides, COS (200 mg/kg/d) was administered to COS and CdCOS groups five times a week for 4 weeks. Then, they were decapitated and hippocampal/cerebral cortex tissue samples were taken for measurement of GSH levels, CAT and SOD activities, MDA values, TNF-α, IL-6, and IL-10 levels as well as SYP immunoreactivity. Although tissue GSH levels were determined the lowest in the Cd group, these values were attenuated with COS treatment in the CdCOS group (p

The present study aimed to reduce the parotid gland dose in the hippocampus avoidance with whole-brain radiotherapy (HA-WBRT) using the helical tomotherapy (HT). Ten patients who had previously undergone WBRT were randomly selected and enrolled in this study. During the treatment planning, two different techniques to the jaw were applied for each patient, namely, 1.0 cm fixed jaw and 2.5 cm dynamic jaw. To efficiently reduce the dose in the bilateral parotid glands, directional block (DB) mode was set. The DB is a function of a treatment planning system for the dose reduction in organs at risk. The standard HA-WBRT plan which did not reduce the parotid gland dose was also designed to compare the plan quality. Compared with the standard HA-WBRT plan, the parotid gland dose could be reduced by approximately 70% without extending the delivery time by adding the parotid gland on the DB mode to the dose constraint. In addition, the differences in dosimetric parameters observed between the plans employing the 1.0 cm fixed jaw and 2.5 cm dynamic jaw were almost negligible. Moreover, delivery time in the 2.5 cm dynamic jaw could be greatly reduced by 60% compared with that in the 1.0 cm fixed jaw.

This study aimed to explore the effect and mechanism of lidocaine pretreatment combined with dexmedetomidine on oxidative stress in patients with intracranial aneurysm clipping. Many studies have used various drugs such as lidocaine to explore the effect and mechanism of lidocaine pretreatment. A total of 80 patients with intracranial aneurysm clipping surgery were randomly divided into 4 groups: the single lidocaine group, single dexmedetomidine group, lidocaine combined with dexmedetomidine group, and control group. The thread embolism method was used to establish a stable intracranial aneurysm model of Hashimoto rats. Fifty adult rats were randomly divided into a sham operation group, ligation of the left common carotid artery and bilateral posterior branch of renal artery, lidocaine group, dexmedetomidine group, and lidocaine combined with dexmedetomidine group. The colorimetric method was used to determine the oxidative stress indicators in brain tissue: MDA content, SOD activity, and T-AOC content. The western blot method characterized the protein levels related to oxidative stress: nNOS, iNOS, and NADPH oxidase subunits p22phox, gp91phox, and p47phox. The differences in each index between the groups were statistically significant ( P < 0.05 ). Animal experiment results revealed that the content of MDA in the brain tissue of rats in the LD group was significantly lower than that in the single-drug group and sham group. The T-AOC and SOD concentrations in the LD group were significantly higher than those in the single-drug group and sham group, and the differences between the groups were statistically significant ( P < 0.05 ). The protein expression of the LD group was significantly lower than that of the drug-alone group and model group, and the difference between groups was statistically significant ( P < 0.05 ). To sum up, lidocaine pretreatment combined with dexmedetomidine can effectively maintain the hemodynamic stability of patients with intracranial aneurysm clipping and reduce postoperative oxidative stress response. Its mechanism of action may be related to the inhibition of oxidative stress damage mediated by nNOS, iNOS, and p22phox, gp91phox, and p47phox in the hippocampus. Our study has significant and applicable medical aspects in lidocaine pretreatment combined with dexmedetomidine on oxidative stress in patients.

Background: Oxidative stress plays a major role in Alzheimer’s disease (AD) pathogenesis, and thus, antioxidant glutathione (GSH) has been actively investigated in mitigating the oxidative load. Significant hippocampal GSH depletion has been correlated with cognitive impairment in AD. Furthermore, postmortem studies indicated alterations in cellular-energy metabolism and hippocampal pH change toward alkalinity in AD. Objective: Concurrent analysis of hippocampal GSH and pH interplay in vivo on the same individual is quite unclear and hence requires investigation to understand the pathological events in AD. Methods: Total 39 healthy old (HO), 22 mild cognitive impairment (MCI), and 37 AD patients were recruited for hippocampal GSH using 1H-MRS MEGA-PRESS and pH using 2D 31P-MRSI with dual tuned (1H/31P) transmit/receive volume head coil on 3T-Philips scanner. All MRS data processing using KALPANA package and statistical analysis were performed MedCalc, respectively and NINS-STAT package. Results: Significant GSH depletion in the left and right hippocampus (LH and RH) among MCI and AD study groups as compared to HO was observed, whereas pH increased significantly in the LH region between HO and AD. Hippocampal GSH level negatively correlated with pH in both patient groups. The ROC analysis on the combined effect of GSH and pH in both hippocampal regions give accuracy for MCI (LH: 78.27%; RH: 86.96%) and AD (LH: 88%; RH: 78.26%) groups differentiating from HO. Conclusion: Outcomes from this study provide further insights to metabolic alterations in terms of concurrent assessment of hippocampal GSH and pH levels in AD pathogenesis, aiding in early diagnosis of MCI and AD.

Purpose The molecular mechanisms by which physical exercise produces beneficial effects on pathological features and behavioral symptoms of Alzheimer's disease (AD) are not well understood. Herein, we examined whether regular moderate exercise could improve cognitive function and produce transcriptomic responses in the brain. Methods Four groups of mice were studied: non-transgenic control (Non-Tg), mice expressing the human presenilin-2 wild type (Tg-PS2w), mice expressing the human presenilin-2 with the N141I mutation (Tg-PS2m), and Tg-PS2m that were subjected to treadmill exercise (TE) at a speed of 10 m/min for 50 min/day, 5 days/week, for 6 weeks (Tg-PS2m/Ex). Results Tg-PS2m/Ex mice exhibited increased preference in exploring a novel object than Tg-PS2m in the novel object recognition test (NORT), whereas differences observed in the water maze test and passive avoidance test were not significant. Western blot and histological analyses using amyloid oligomer (A11) and Aβ (6E10) antibody indicated that amyloid oligomer-reactive bands and plaque deposition in the hippocampus were reduced, though not significantly, after TE. Transcriptomic (RNA-sequencing) analysis and subsequent protein analysis revealed that the cell cycle regulatory gene, Cdc28 protein kinase regulatory subunit 2 (Cks2), was decreased, and the cell cycle- and apoptotic cell death-related factors, including cyclin D1, proliferating cell nuclear antigen, and cleaved caspase-3 were increased in the hippocampus of Tg-PS2m, whereas TE reversed their altered expression. Conclusion These results support the hypothesis that the pathological features and behavioral symptoms of AD caused by accumulation of amyloid beta-peptide in hippocampus, causing aberrant cell cycle re-entry and apoptosis, can be reversed by regular exercise.

Epilepsy is one of the most common chronic neurological diseases. There is increasing evidence for ferroptosis playing an important role in the occurrence and development of epilepsy. Vitamin E is a common fat-soluble antioxidant that can regulate ferroptosis. The aim of this study was to investigate the effects of vitamin E on ferroptosis of hippocampal neurons in epileptic rats. Sixty-four male Sprague-Dawley (SD) rats were randomly divided into control, pentylenetetrazol (PTZ; 35 mg/kg), vitamin E (200 mg/kg) + PTZ, and Ferrostatin-1 (Fer-1; 2.5 μmol/kg) + PTZ groups, with drugs administered intraperitoneally 15 times every other day for 29 days. The behavioral manifestations (epileptic score, latency, and number of seizures in 30 min) and EEG changes were observed and recorded. Nissl staining and electrophysiological recording were used to assess neuronal damage and excitability in the hippocampal CA1 region, respectively. The levels of iron, glutathione (GSH), and malondialdehyde (MDA) in the hippocampus were assessed by spectrophotometry. Immunofluorescence staining was used to detect lipoxygenase 15 (15-LOX) expression. Western blot was used to determine glutathione peroxidase 4 (GPX4) and 15-LOX protein levels. Vitamin E treatment was associated with decreased epileptic grade, seizure latency, and number of seizures in the PTZ-kindled epileptic model. Vitamin E treatment also decreased 15-LOX expression, inhibited MDA and iron accumulation, and increased GPX4 and GSH expression. In conclusion, vitamin E can reduce neuronal ferroptosis and seizures by inhibiting 15-LOX expression.

Our previous studies have shown that the nutritional properties of peanut meal after fermentation are markedly improved. In this study, in order to facilitate the further utilisation of peanut meal, we investigated the effects of its fermentation extract by Bacillus natto (FE) on cognitive ability, antioxidant activity of brain and protein expression of hippocampus of ageing rats induced by d-galactose. Seventy-two female sd rats aged 4–5 months were randomly divided into six groups: normal control group, ageing model group, FE low-dose group, FE medium-dose group, FE high-dose group and vitamin E positive control group. Morris water maze (MWM) test was performed to evaluate their effects on learning and memory ability in ageing rats. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of brain, HE staining and the expression of γ-aminobutyric acid receptor 1 (GABABR1) and N-methyl-d-aspartic acid 2B receptor in the hippocampus of rats were measured. The results show that FE supplementation can effectively alleviate the decrease of thymus index induced by ageing, decrease the escape latency of MWM by 66·06 %, brain MDA by 28·04 %, hippocampus GABABR1 expression by 7·98 % and increase brain SOD by 63·54 % in ageing model rats. This study provides evidence for its anti-ageing effects and is a research basis for potential nutritional benefits of underutilised food by-products.

Objectives This study investigated the involvement of heme oxygenase-1 (HO-1) in the antidepressant-like effects of ursolic acid (UA), a plant-derived compound with neuroprotective and antidepressant-like properties. Methods Mice received intracerebroventricular injections of zinc protoporphyrin IX (ZnPP) or cobalt protoporphyrin IX (CoPP) to inhibit or induce HO-1, respectively, together with effective (0.1 mg/kg, p.o.) or sub-effective (0.01 mg/kg, p.o.) doses of UA or fluoxetine (10 mg/kg, p.o.). Immobility time was assessed using the tail suspension test (TST) and the ambulatory behaviour with the open field test. HO-1 immunocontent was evaluated in mice hippocampus and prefrontal cortex. Key findings ZnPP prevented the anti-immobility effects of UA and fluoxetine. Combined treatment with a sub-effective dose of CoPP and UA synergistically exerted antidepressant-like effects in the TST. Acute administration of UA or CoPP, but not fluoxetine, increased the HO-1 immunocontent in the hippocampus. None of the treatments altered the HO-1 immunocontent in the prefrontal cortex. Conclusions In conclusion, this work shows that increased hippocampal HO-1 content and activity mediate the antidepressant-like effect of UA in the TST.

Salt or sodium chloride (NaCl) is an additive to give food a salty taste. The use of salt in everyday life is difficult to avoid. Salt has both good and bad effects on the body. The electrolyte content of salt can help launch metabolism in the body, whereas if the body contains too much salt it will cause heart attacks and hypertension. The dose of salt consumption that has been set by the government is 5g/day. This study was conducted to examine the effect of consuming excessive sodium chloride (NaCl) on the ability to smell and to what extent it damages cells in the hippocampus of mice (Mus musculus). The method of this study was CRD (completely randomized design) with 6 replications, 1 group control and 3 repetitions induced by sodium chloride (NaCl) is 260mg/gBB (P1), 520mg/gBB (P2), and 780mg/gBB (P3). The parameters of this study are neurosensory coordination in the form of olfactory response of mice (Mus musculus) to ammonia and cell disruption in the hippocampus (DG & CA) which were observed by histological preparations of Hematoxylin eosin (HE) staining. The results of this study indicate the presence of olfactory disorders in mice (Mus musculus) and cell death in the hippocampus also increased due to excessive sodium chloride (NaCl) induction. The more salt is consumed in daily life, it will disrupt the cells in the hippocampus.

To fully understand the mechanisms governing learning and memory, animal models with minor interindividual variability and higher cognitive function are required. THA rats established by crossing those with high learning capacity exhibit excellent learning and memory abilities, but the factors underlying their phenotype are completely unknown. In the current study, we compare the hippocampi of parental strain Wistar rats to those of THA rats via metabolomic analysis in order to identify molecules specific to the THA rat hippocampus. Higher branched-chain amino acid (BCAA) levels and enhanced activation of BCAA metabolism-associated enzymes were observed in THA rats, suggesting that acetyl-CoA and acetylcholine are synthesized through BCAA catabolism. THA rats maintained high blood BCAA levels via uptake of BCAAs in the small intestine and suppression of BCAA catabolism in the liver. Feeding THA rats with a BCAA-reduced diet decreased acetylcholine levels and learning ability, thus, maintaining high BCAA levels while their proper metabolism in the hippocampus is the mechanisms underlying the high learning ability in THA rats. Identifying appropriate BCAA nutritional supplements and activation methods may thus hold potential for the prevention and amelioration of higher brain dysfunction, including learning disabilities and dementia.

Evidence suggests that oxidative stress plays an important role in the development of anxiety and depression. The aim of the present study was to investigate whether methyl donors supplementation could exert beneficial effects on hippocampal oxidative stress, anxiety and depression in chronically high fructose-treated rats, a new animal model of anxiety and mood disorders. Rats were divided into two groups and treated for 10 weeks as follows: Group 1 represents the control group and Group 2 was treated with 23% fructose. After 10 weeks, the fructose-fed animals were divided into two groups and treated for 8 weeks as follows: Group 2 continued to receive fructose while Group 3 was treated with methyl donors and fructose. High fructose-fed rats showed increases in glucose, triglycerides, total cholesterol as well as in the final body weight and the adipose tissue weight. High fructose induced anxiety- and depression-like behaviors. High fructose caused an increase of the nitrite content and the Malondialdehyde (MDA) levels in the hippocampus tissue in association with an induction of damage in the dorsal hippocampus neurons. The 8-weeks dietary supplementation with methyl donors normalized the depression-like behavior, oxidative stress in the hippocampus, reversed the damage observed in the hippocampal neurons. These findings demonstrate that high fructose induced depression in association with the induction of a hippocampal oxidative stress. The anti-depressive action of methyl donors appears to be associated to their anti-oxidative properties since they normalized the nitrite content and the MDA levels at the hippocampus in the high fructose-fed female rats.

This study examined the effects of a two-week running intervention on depressive symptoms and structural changes of different subfields of the hippocampus in young adults from the general population. The intervention was realized in small groups of participants in a mostly forested area and was organized into seven units of about 60 min each. The study design included two intervention groups which were tested at three time points and which received the intervention time-delayed: The first group between the first and the second time point, and the second group between the second and the third time point (waiting control group). At each test session, magnetic resonance imaging (MRI) was performed and symptoms related to depression were measured by means of the Center for Epidemiological Studies Depression (CES-D) Scale. Results revealed a significant reduction of CES-D scores after the running intervention. The intervention also resulted in significant increases in the volume of the hippocampus, and reductions of CES-D scores right after the intervention were associated with increases in hippocampal volume. These findings add important new evidence on the beneficial role of aerobic exercise on depressive symptoms and related structural alterations of the hippocampus.

Preservation of the brain is important to reducing recurrent seizures and other neurological sequelae after status epilepticus (SE). Medical ozone (MedO3) shows antioxidant, anti-inflammatory and anti-apoptotic properties in the human body. In this study, it was aimed to understand the neuroprotective potential of MedO3 in the acute period after SE. Mature rats of Wistar Albino were used for the study. Group design O3 + SE: SE induced after MedO3, O3: MedO3 alone was given, SE: SE only induced, SE + O3; MedO3 given after SE, C: control and S: sham control group. SE was induced with lithium-pilocarpine experimental model and evaluated on the Racine scale. Peripheral blood samples and brain tissue samples were taken before decapitation. Histopathological evaluation of the hippocampus of the rats given medical O3 before and after SE were studied. The highest peripheral blood oxidative stress index (OSI) was found in SE group. The OSI level in O3 + SE and SE + O3 was significantly higher than SE/C/S. Gene expressions of TNF-α and IL-1β mRNA were significantly higher in SE compared to other groups. Histopathologically; eosinophilia, cellular shrinkage and interstitial oedema were detected in the most severe SE and to a lesser extent in O3 + SE/ SE + O3. MedO3 reduced SE-induced oxidative damage, neuroinflammation and neuronal injury and contributed positively to neuroprotection.

BACKGROUND AND PURPOSE There is a scarcity of information regarding the role of prothrombin kringle-2 (pKr-2), which can be generated by active thrombin, in hippocampal neurodegeneration and Alzheimer's disease (AD). EXPERIMENTAL APPROACH To assess the role of pKr-2 in association with the neurotoxic symptoms of AD, we determined pKr-2 protein levels in post-mortem hippocampal tissues of patients with AD and the hippocampi of five familial AD (5XFAD) mice compared with those of age-matched controls and wild-type (WT) mice, respectively. In addition, we investigated whether the hippocampal neurodegeneration and object memory impairments shown in 5XFAD mice were mediated by changes to pKr-2 up-regulation. KEY RESULTS Our results demonstrated that pKr-2 was up-regulated in the hippocampi of patients with AD and 5XFAD mice, but was not associated with amyloid-β aggregation in 5XFAD mice. The up-regulation of pKr-2 expression was inhibited by preservation of the blood-brain barrier (BBB) via addition of caffeine to their water supply or by treatment with rivaroxaban, an inhibitor of factor Xa that is associated with thrombin production. Moreover, the prevention of up-regulation of pKr-2 expression reduced neurotoxic symptoms, such as hippocampal neurodegeneration and object recognition decline due to neurotoxic inflammatory responses in 5XFAD mice. CONCLUSION AND IMPLICATIONS We identified a novel pathological mechanism of AD mediated by abnormal accumulation of pKr-2, which functions as an important pathogenic factor in the adult brain via blood brain barrier (BBB) breakdown. Thus, pKr-2 represents a novel target for AD therapeutic strategies and those for related conditions.

Since the NAD+-dependent histone deacetylases sirtuin-1 (SIRT1) and sirtuin-2 (SIRT2) are critically involved in epigenetics, endocrinology and immunology and affect the longevity in model organisms, we investigated their expression in brains of 3-month-old and 14–15 months old rat model of depression Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats. In view of the dysregulated NPY system in depression, we also studied NPY in young and old FSL to explore the temporal trajectory of depressive-like–ageing interaction. Sirt1, Sirt2 and Npy mRNA were determined using qRT-PCR in prefrontal cortex (PFC) from young and old FSL and FRL, and in hippocampi from young FSL and FRL. PFC: Sirt1 expression was decreased in FSL (p = 0.001). An interaction between age and genotype was found (p = 0.032); young FSL had lower Sirt1 with respect to both age (p = 0.026) and genotype (p = 0.001). Sirt2 was lower in FSL (p = 0.003). Npy mRNA was downregulated in FSL (p = 0.001) but did not differ between the young and old rat groups. Hippocampus: Sirt1 was reduced in young FSL compared to young FRL (p = 0.005). There was no difference in Sirt2 between FSL and FRL. Npy levels were decreased in hippocampus of young FSL compared to young FRL (p = 0.003). Effects of ageing could not be investigated due to loss of samples. To conclude, i this is the first demonstration that SIRT1 and SIRT2 are changed in brain of FSL, a rat model of depression; ii the changes are age-dependent; iii sirtuins are potential targets for treatment of age-related neurodegenerative diseases.

A high proportion of patients with drug-resistant temporal lobe epilepsy (TLE) show focal relative hypometabolism in the region of the epileptogenic zone on [18F]-Fluorodeoxyglucose positron emission tomography (FDG PET). However, whether focal (hypo)metabolism changes over time has not been well studied. We analysed repeated [18F]-FDG PET scans of patients with TLE to determine longitudinal changes in glucose metabolism. Adults (n = 16; 9 female, 7 male) diagnosed with drug resistant chronic TLE were assessed. Each patient had two [18F]-FDG PET scans that were 2-95 months apart. Region-of-interest analysis was performed on MR images onto which PET scans were coregistered to determine the relative [18F]-FDG uptake (normalised to pons) in the bilateral hippocampi and temporal lobes. Statistical Parametric Mapping analysis investigated global voxel-wise changes in relative metabolism between timepoints. Normalised [18F]-FDG uptake did not change with time in the ipsilateral (baseline 1.14 ± 0.03, follow-up 1.19 ± -0.04) or contralateral hippocampus (baseline 1.18 ± 0.03, follow-up 1.19 ± 0.03). Uptake in the temporal neocortex also remained stable (ipsilateral baseline 1.35 ± 0.03, follow-up 1.30 ± 0.04; contralateral baseline 1.38 ± 0.04, follow-up 1.33 ± 0.03). The was no relationship between change in uptake on the repeated scans and the time between the scans. SPM analysis showed increases in metabolism in the ipsilateral temporal lobe in 2/16 patients. No areas of decreased metabolism concordant to the epileptogenic zone were identified. [18F]-FDG uptake showed no significant changes over time in patients with drug-resistant TLE. This suggests that repeating FDG-PET scans in patients with subtle or no hypometabolism is of low clinical yield.

Objective: Diet rich in fat is one of the main risk factor for the development of Alzheimer’s disease. Studies have shown that diet rich in fat disrupts memory and learning. The present study evaluates the ameliorative role of Ginkgobiloba and Rosuvastatin against high fat diet induced neurotoxicity in CA1 (Corona Ammonis) region of hippocampus. Materials and Methods: Animals were randomly divided into six groups. Group I received normal diet, Group II received high fat diet, Group III & IV were treated with Ginkgobiloba 50mg/kg and 100mg/kg body weight, and Group V & VI were treated with Rosuvastatin 10mg/kg and 20 mg/kg body weight. All the rats were subjected to spatial learning (Morris water maze). Subsequently, rats were sacrificed and brains were removed. Golgi staining was done and CA1 neurons of hippocampus were traced using camera lucida. Dendritic branching points and dendritic intersections were quantified. Lipid profile and Super oxide (SOD) was also estimated. Results: There was enhancement of spatial learning in treatment group rats. Furthermore, a significant increase in dendritic length and branching points was observed in CA1 region along with significant decrease in the Superoxide dismutase in rats treated with higher dose of Ginkgobiloba and Rosuvastatin. Conclusion: Present study concludes that Ginkgobiloba and Rosuvastatin in higher dose have protective role against high fat diet induced neurotoxicity in CA1 region. Keywords: Ginkgobiloba, Rosuvastatin, Corona ammonis, Morris water maze, Dendritic branching.

Chronic stress increases the production of pro-inflammatory cytokines and oxidative stress in the brain, which underlay cognitive and psychological problems. In addition to the anti-depressants, vitamin D is known to act as an anti-inflammatory and anti-oxidative agent. This study investigates the specific effects of vitamin D in protecting hippocampus and pre-frontal cortex (PFC) against chronic mild stress (CMS)-induced activation of pro-inflammatory cytokines IL-6 and TNF-α and decreasing the activation of anti-oxidative enzymes super oxide dismutase (SOD) and glutathione peroxidase (GPx). Rats were exposed to CMS for 3 weeks. Two groups of rats received vitamin D (5 and 10 μg/kg) and another received fluoxetine (5 mg/kg) along with CMS. Control groups were not exposed to CMS, but received treatments similar to CMS groups. Serum corticosterone and IL-6, TNF-α and SOD and GPx levels in the hippocampus and PFC were measured at the end of three weeks. CMS significantly increased corticosterone, IL-6, TNF-α and decreased SOD and GPx levels (P

The diagnostic and clinical overlap of early mild cognitive impairment (EMCI), mild cognitive impairment (MCI), late mild cognitive impairment (LMCI) and Alzheimer disease (AD) is a vital oncological issue in dementia disorder. This study is designed to examine Whole brain (WB), grey matter (GM) and Hippocampus (HC) morphological variation and identify the prominent biomarkers in MR brain images of demented subjects to understand the severity progression. Curve evolution based on shape constraint is carried out to segment the complex brain structure such as HC and GM. Pre-trained models are used to observe the severity variation in these regions. This work is evaluated on ADNI database. The outcome of the proposed work shows that curve evolution method could segment HC and GM regions with better correlation. Pre-trained models are able to show significant severity difference among WB, GM and HC regions for the considered classes. Further, prominent variation is observed between AD vs. EMCI, AD vs. MCI and AD vs. LMCI in the whole brain, GM and HC. It is concluded that AlexNet model for HC region result in better classification for AD vs. EMCI, AD vs. MCI and AD vs. LMCI with an accuracy of 93, 78.3 and 91% respectively.

To evaluate the effects of dexmedetomidine (Dex) and oxycodone (Oxy) on neurocognitive and inflammatory response after tourniquet-induced ischemia–reperfusion (I/R) injury. C57/BL6 mice were used to construct the mouse model of tourniquet-induced I/R injury. Mice (n = 48) were randomly divided into sham, I/R, Dex or Oxy group. Morris water maze test was performed to assess the spatial learning and memory function. The expression of NF-κB, TLR4, NR2B, M1 (CD68 and TNF-α) and M2 (CD206 and IL-10) polarization markers in mice hippocampus were detected by western blot or immunofluorescent staining. Spontaneous excitatory post-synaptic currents (sEPSCs) were recorded by electrophysiology. Dex treatment alleviated I/R-induced declines in learning and memory (p

The rise in annual production and applications of aluminum nanoparticles leads to elevation of the environmental and occupational exposures to this substance and might raise potential risk to the human health. Aluminum toxicity was suggested to have a role in the pathogenesis of Alzheimer’s disease. Considering the physicochemical properties of aluminum nanoparticle, such as its size, high reactivity, and high specific surface area, there is a concern about the impact of these nanoparticles on brain function. This study was designed to evaluate the effect of a 5-day oral gavage of aluminum oxide nanoparticle (ALNP) on memory and Akt/GSK-3β pathway as well as cleaved caspase-3 signaling in the hippocampus. Adult male NMRI mice were treated with ALNP in doses 5 and 10 mg/kg/oral gavage for 5 days. The novel object recognition (NOR) test session was performed on day 5. Following the behavioral assessments, the hippocampi were assessed for Akt/GSK-3β signaling using western blot technique. The results showed that ALNP oral gavage in doses 5 and 10 mg/kg impairs NOR memory in mice. Furthermore, it decreased the ratio of active to total level of Akt in the hippocampus while increased GSK-3β level in the hippocampus. The memory impairing effect of ALNP coincided with a dose-dependent increase in cleaved caspase-3. This study showed the deregulation of Akt/GSK-3β signaling and apoptosis in the hippocampus following oral aluminum oxide nanoparticle (ALNP) exposure.

The use of Monosodium Glutamate (MSG) as a food flavor enhancer is increasing worldwide despite its neurotoxic effects. Fluoxetine (FLX) and Rosemary extract (RE) are known to have beneficial neuroprotective properties. Rats were divided into five groups: control group; MSG group, rats received 2 g/kg/day intraperitoneal (i.p.) injections of MSG for seven days; RE/MSG group, rats received 50 mg/kg/day of oral RE for 28 days starting prior to MSG; FLX/MSG group, rats received 10 mg/kg/day of oral FLX for 28 days beginning before MSG; and RE/FLX/MSG group, received combined treatments as mentioned above. Rats underwent the Barnes maze test, in addition to histopathological, immunohistochemical, morphometric and ultrastructural evaluations for their hippocampi. MSG increased the number of errors and escaped latency in the Barnes maze test that was significantly minimized in the three treatment groups. The MSG group exhibited pyramidal cell (PC) degeneration, shrunken glial cells and massive vascular dilatation that were improved with RE and/or FLX treatment. The number of glial fibrillary acidic protein (GFAP)-immunopositive cells were increased, and the number of PCs was decreased in the MSG group, while these values were significantly reversed with the three treatment groups with the most significant improvement at RE/FLX/MSG one. Ultrastructurally, PCs were shrunken with degenerated nuclei, dilated endoplasmic reticulum, swollen mitochondria, and vacuolations in the MSG group that were improved with RE and/or FLX. In conclusion, the combined RE and FLX treatment can ameliorate the toxic effect of MSG on rat hippocampus probably through its antioxidant and anti-inflammatory effects.

To explore the protective mechanism of acupuncture plus mild hypothermia for cerebral ischemia-reperfusion injury (CIRI) by observing the effects of acupuncture plus mild hypothermia on miRNA-204 and its target gene expressions in CIRI rat brain tissues. Sixty Sprague-Dawley rats were divided into a blank control group, a sham operation group, a model group, an acupuncture group, a mild hypothermia group and an acupuncture plus mild hypothermia group according to the random number table method (n=10). Except for the blank control group and the sham operation group, rats in the other 4 groups received CIRI modeling. After the model was successfully established, rats in the blank control group were bred routinely for 72 h without any interventions; rats in the sham operation group and the model group were bred routinely for 72 h, and only received binding without other interventions after surgery; rats in the acupuncture group were bred routinely for 72 h, and received acupuncture at Dazhui (GV 14), Baihui (GV 20) and Shuigou (GV 26) after binding; rats in the mild hypothermia group were bred routinely for 72 h, and received mild hypothermia intervention for 72 h after binding; rats in the acupuncture plus mild hypothermia group were bred routinely for 72 h, followed by receiving acupuncture as in the acupuncture group and mild hypothermia therapy as in the mild hypothermia group after binding. The neurological impairment score, cerebral infarction area ratio, the expressions of miRNA-204 and its target genes including Map3k8, Ntrk2 and Ppp3r1 in the ischemic hippocampus of each group were observed after 72 h of intervention. Before intervention, compared with the blank control group and the sham operation group, the neurological impairment scores and the infarction area ratios of the modelled rats were statistically significantly increased (all P

Estradiol (E2) is involved in the regulation of emotional behavior, cognitive function, and neuroplasticity. However, peripheral E2 and central E2 levels do not always fluctuate together. The relationships of peripheral and central E2 with cognitive function are not clear. The aim of this study was to investigate whether peripheral E2, hippocampal E2, or both play a critical role in novel object recognition (NOR), and whether Kalirin-7, an important regulator of spine plasticity, is involved in the modulation of E2 on cognitive behavior. Our results showed that ovariectomy (OVX) significantly reduced serum E2 levels in the 14 weeks following the procedure. However, hippocampal E2 levels did not decrease in the OVX group compared to the sham group until after 14 weeks. Consistent with the changes in hippocampal E2 levels, the investigation ratio in the NOR test and hippocampal Kalirin-7 expression was also not lower in the OVX group than in the sham group until 14 weeks after the procedure. To confirm the relationship between hippocampal E2 levels and NOR ability, we inhibited the production of hippocampal E2 via microinjection of letrozole (LTZ; an aromatase inhibitor) into the hippocampi of rats in the control group and 8-week OVX group. The data indicated that a reduction in E2 levels in the hippocampus significantly impaired NOR ability and simultaneously decreased Kalirin-7 levels in the hippocampus. In conclusion, our study strongly demonstrates that hippocampal E2, but not peripheral E2, plays a critical role in NOR ability and that Kalirin-7 may be involved in this mechanism. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

We aimed to assess the effects of dexmedetomidine (DEX) on postoperative cognitive function of sleep deprivation (SD) rats based on changes in inflammatory response. Male rats were randomly divided into blank control (C), SD, DEX, and SD+DEX groups. The SD model was established through intraperitoneal injection of DEX. The escape latency was detected through Morris water maze test daily, and the mechanical withdrawal threshold and thermal withdrawal latency were detected for 8 d. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in hippocampus homogenate were determined, and the morphological changes in neurons were detected through Nissl staining. The concentration of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 in the hippocampus was detected by enzyme-linked immunosorbent assay, and the Rac1/protein kinase B (AKT)/nuclear factor-κB (NF-κB) expressions were detected by Western blotting. The changes in immunofluorescence localization of NF-κB were observed by confocal microscopy. Compared with SD group, the escape latency was shortened, original platform-crossing times increased, MDA content declined, SOD activity rose, neurons were arranged orderly and number of Nissl bodies increased in the hippocampal CA1 region, levels of IL-1β, TNF-α, and IL-6 in the hippocampus decreased, Rac1/AKT/NF-κB expressions were down-regulated, and proportion of NF-κB entering the nucleus declined in SD+DEX group (P

Purpose To evaluate the effectiveness of Kami Guibi‐tang (KGT) in the treatment of mild cognitive impairment (MCI) using magnetic resonance imaging (MRI) on brain metabolites, neurotransmitter, and cerebral blood flow (CBF). Methods We randomly allocated a total of 30 MCI patients to a KGT (N = 16) or a placebo (N = 14) group and performed MRI scans before and after 24 weeks of treatment. The participants underwent brain magnetic resonance spectroscopy and MRI scans to obtain brain metabolites using Point‐RESolved Spectroscopy (PRESS) single‐voxel spectroscopy, gamma‐aminobutyric acid (GABA) neurotransmitter using Mescher–Garwood PRESS, and CBF using pseudocontinuous arterial spin labeling sequences using a 3.0 Tesla MRI system. We analyzed metabolite and neurotransmitter levels and CBF using repeated‐measure analysis of variance to evaluate between‐subject group effect, within‐subject treatment condition effect, and interaction of group by condition (group x condition). Results The GABA+/creatine (Cr) ratio values were not significantly different between the before and after treatment conditions. The glutamate complex/Cr ratio difference before and after treatment was lower in the KGT group than in the placebo group, but was not statistically significant (p = 0.077). The result of region of interest–based CBF measurement showed that CBF values were significantly lower after treatment at Cluster 2 for the KGT group (p = 0.003) and the placebo group (p = 0.011), at hippocampus for the KGT group (p = 0.004) and the placebo group (p = 0.008), and at the fusiform gyrus for the KGT group (p = 0.002). Furthermore, the absolute CBF difference before and after treatment in the fusiform gyrus was significantly lower in the KGT group than in the placebo group (p = 0.024). Conclusions Although a KGT treatment of 24 weeks showed some significant impact on the level of CBF, the Korean version of the mini‐mental state examination score was not significantly different between before and after treatment conditions, indicating that there was no memory function improvement after treatment in amnestic MCI patients. Therefore, further studies should be performed with a relatively larger population and extending the duration of the KGT treatment.

Введение. Посттравматическое стрессовое расстройство (ПТСР) формируется спустя длительный срок после переживания психической травмы. Имеются данные о низком уровне серотонина у больных ПТСР, который часто сочетается с окислительным стрессом, обусловленным нейровоспалением. Представляется актуальным поиск эффективных средств немедикаментозной коррекции ПТСР. Одним из высокоэффективных и наиболее широко используемых методов является адаптация к периодической гипоксии (АПГ). Цель работы - исследование влияния АПГ на обмен серотонина и показатели окислительного стресса в гиппокампе животных при экспериментальном ПТСР. Методика. Исследование выполнено на 34 половозрелых самцах крыс Вистар, которые были разделены на 4 группы («Контроль», «ПТСР», «АПГ», «ПТСР+АПГ»). В качестве модели экспериментального ПТСР была использована модель хронического предаторного стресса, где животные подвергались «запаху хищника» (кошачьей мочи) по 10 мин в течение 10 сут. После этого крыс адаптировали к периодической гипоксии в гипобарической барокамере в течение 14 сут, начиная с 30 мин в 1-е сут на симулированной высоте 1000 м, с постепенным увеличением «высоты» и времени экспозиции до 4000 м в течение 4 ч на 5-е сут и в последующие дни. Поведенческие реакции животных изучали при помощи теста «приподнятый крестообразный лабиринт» (ПКЛ). Концентрацию серотонина и его метаболита 5-гидроксииндолуксусной кислоты (5-ГИУК) определяли методом высокоэффективной жидкостной хроматографии. Содержание первичных и вторичных продуктов перекисного окисления липидов (ПОЛ) оценивали спектрофотометрически согласно методике И.А. Волчегорского и соавт. Уровень окислительной деструкции белков оценивали по содержанию карбонилированных белков. Результаты. При тестировании в ПКЛ было установлено, что у животных через 14 сут после завершения предаторного стресса по сравнению с контролем наблюдалось усиление тревожности, которое ограничивалось курсом АПГ. Одновременно с этим установлено снижение содержания серотонина и повышение уровня 5-ГИУК, что привело к существенному повышению метаболического индекса серотонина. Курс АПГ не привел к статистически значимым изменениям содержания серотонина и его метаболита по сравнению с контролем. В группе «ПТСР+АПГ» по сравнению с группой «ПТСР» отмечено повышение концентрации серотонина при одновременном снижении 5-ГИУК и метаболического индекса серотонина. Исследование окислительного стресса в гиппокампе животных с ПТСР-подобным состоянием показало повышение базального уровня карбонилированных белков по сравнению с контролем и увеличение содержания вторичных продуктов ПОЛ. Заключение. При экспериментальном ПТСР в гиппокампе снижение содержания серотонина ассоциировано с усилением его метаболизма, что сопровождается усилением окислительного стресса. Нейропротекторное действие АПГ выражается в нивелировании окислительного стресса в гиппокампе. Background. Post-traumatic stress disorder (PTSD) develops long after a mental traumatic event. In patients with PTSD, low serotonin levels often combine with oxidative stress-induced inflammation. Searching for effective non-pharmacological therapies for PTSD is important. Adaptation to intermittent hypoxia (AIH) is one of highly effective and widely used methods. The aim of this study was to elucidate the effect of AIH on serotonin metabolism and oxidative stress in the hippocampus of rats with PTSD. Methods. The study was performed on 34 sexually mature male Wistar rats divided into 4 groups: control, PTSD, AIH, and PTSD+AIH. Experimental PTSD was modeled with chronic predator stress, where animals were exposed to predator smell (cat urine) for 10 days, 10 min daily. Then rats were conditioned in a hypobaric altitude chamber for 14 days at a 1,000-m simulated altitude for 30 min on day 1 with altitude and duration progressively increasing to 4,000 m for 4 h on day 5 and all the remaining days. Behavioral reactions of rats were studied with the elevated plus maze (EPM) test. Concentrations of serotonin and the serotonin metabolite, 5-hydroxy indole acetic acid (5-HIAA), were measured by high-performance liquid chromatography. Contents of primary and secondary lipid peroxidation (LPO) products were measured spectrophotometrically according to the method of I.A. Volchegorskiy et al. The oxidative damage to proteins was assessed by the content of carbonylated proteins. Results. The EPM test showed that 14 days after the predator stress completion, the anxiety level was higher than in control, and this effect was alleviated by AIH. Also, stress-exposed rats had lower serotonin and higher 5-HIAA concentrations, which resulted in a significantly higher serotonin metabolic index compared to the control. The course of AIH did not cause any significant changes in concentrations of serotonin and its metabolite as compared to the control. In the PTSD + AIH group compared to the PTSD group, the serotonin concentration was increased whereas the 5-HIAA concentration and the metabolic serotonin index were decreased. Studying oxidative stress in the hippocampus of rats with the PTSD-like condition showed that both the basal level of carbonylated proteins and the content of LPO secondary products were increased compared to the control group. Conclusions. In experimental PTSD in the hippocampus, the decrease in serotonin content was associated with the increase in its metabolism and with potentiation of oxidative stress. The neuroprotective effect of AIH was evident as alleviation of oxidative stress in the hippocampus.

This study aims to investigate the neuroprotective effect of wild lowbush blueberry on CIRI in rats. Accordingly, CIRI and reperfusion were induced in rats for 60 min and 24 h, respectively. Then, the mechanisms of the neuroprotective effects of BBE were investigated in the injury through evaluating miR-146a, miR-21, and their targets in a CIRI rat model. After that, the BBE (30, 60, and 120 mg/kg b.wt) was intraperitoneally injected for 14 days, then CIRI was induced by BCCAO for 60 min for ischemic stroke and reperfusion for 24 h. Several parameters including the oxidative stress levels in the hippocampus and serum were measured 24 h after the CIRI. The findings showed that the BBE significantly decreased the levels of malondialdehyde (MDA) and nitric oxide (NO) and increased ferric ion reducing antioxidant power (FRAP) levels in the hippocampus and serum following the stroke. The BBE also maximized the miR-146a and miR-21 expressions and moderated iNOS and TNF-α expressions in the hippocampus. Likewise, the BBE enlarged the CA1 and CA3 domains of the post-stroke pyramidal cell layers of the hippocampus. Overall, the results revealed that BBE had potent neuroprotective efficacy against CIRI via the effective modulation of neuroinflammatory cascades and protected neurons against ischemic death.

Aims Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism. Methods The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20 days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot. Results GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ. Conclusions Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.

The aim of research was to study structural changes and give a morphometric characteristic of the edemaswelling manifestations of the dentate gyrus (DG) of the hippocampal formation in sexually mature white rats after common carotid artery occlusion (OCCA) of different duration and ligation (LCCA) of the common carotid arteries.Material and methods. Acute ischemia was simulated in white adult Wistar rats by 20-, 30-, and 40-min occlusion and ligation of the common carotid arteries. Histological (staining with hematoxylin-eosin, according to Nissl), immunohistochemical (NSE, MAP-2, GFAP) and morphometric research techniques were used for morphological investigations. Morphometric analysis of the edema-swelling manifestations was carried out on samples stained with hematoxylin-eosin using plugins of the ImageJ 1.53 program (Find Maxima, Find Foci). Statistical hypotheses (nonparametric tests) were tested using Statistica 8.0 software.Results. After reperfusion, pronounced involution of large zones of edema-swelling occurred in the DG of the hippocampal formation in white rats of the groups I, II, III after 7–14 days, and in rats of the group IV (ligation) the edema-swelling manifestations persisted for 30 days. Similar dynamics was recorded for the molecular and polymorphic layer of the DG, but the values of the integral variable chosen to assess the edema-swelling manifestations (the total intensity of the peak pixels) were different. The largest relative area of the brightest peaks was detected after bilateral ОССА (groups II and III) and LCCA (group IV), the smallest – after unilateral ОССА (group I). It is significant that after mild ischemia (20- and 30-min ОССА), the parameter increased only in 1 and 3 days, and then decreased. After more severe ischemia (40-min ОССА), similar manifestations of overhydration were observed in 1–7 days. With LССА, a high level of DG overhydration was noted throughout the observation period, as evidenced by the high relative area of all the brightest peaks. Statistically significant differences were found when comparing all groups for all periods, between groups in 14 and 30 days, between periods in groups I, II, and III (ANOVA Kruskal–Wallis test; Mann–Whitney U-test).Conclusion. After ОССА and LССА the restoration of the structures of the sensory input of the hippocampus (DG) occurs together with long-term preservation of signs of hyperhydration of the neuropil, perineuronal and perivascular spaces (legs of astrocytes). The extreme degree of these manifestations after LССА evidences a disruption of the drainage-detoxification function of astrocytes. In ОССА, long-term preservation of the edema-swelling manifestations is recommended to be considered as a condition for the implementation of the mechanisms of sanogenesis and restoration of the DG nervous tissue.

INTRODUCTION Bilberry fruit is believed to be a promising factor in the treatment of diabetes mellitus. Chronic hyperglycaemia affects the function of the central nervous system, which may be manifested as changes in hypothalamic insulin signalling. MATERIAL AND METHODS Using DPPH and ABTS assays, total phenolic content in bilberry fruit and its antioxidant activities were examined. The selected biochemical parameters of blood (glucose, fructosamine, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides), as well as the expression of insulin receptors, were studied in the hippocampal CA1 field of healthy and diabetic (streptozotocin-induced; 60 mg kg-1 body weight) Wistar rats fed with bilberry fruit (16 g kg-1 body weight per day; 6 weeks), as well as of the corresponding control groups. RESULTS Biochemical analyses revealed ambiguous results, but a significantly (P

To date, our understanding of the role of abnormal hippocampal volume in imaging studies of insomnia disorders (ID) has remained in apparent contradiction. Given that hippocampal function can be mapped to anatomically defined substructures, the hippocampal substructure volume can be examined in detail at present. In this study, we examined the volumes of hippocampal substructures between IDs and healthy controls (HC) to accurately find hippocampal markers of ID. First, we used the automated hippocampal substructure module in FreeSurfer6.0 to inspect T1-weighted magnetic resonance images between 22 IDs and 30 HC. Then, 12 hippocampal substructures were computed. Volumetric assessment was performed at the hippocampal substructure level between groups. Our study revealed significant reduced volume of the bilateral fimbria in IDs compared with HC (p

A comparative experimental analysis of intensity of nitric oxide (NO) production and the copper content in the tissues of hippocampus of male Wistar rats after modeling of hemorrhagic stroke and brain injury was conducted using EPR spectroscopy. Modeling of hemorrhagic stroke was carried out by microinjection of 500 nl of autologous blood into the brain to a depth of 5.0 mm (hippocampus) on the left side. Brain injury was performed by removing a piece of nerve tissue from 5.0 mm depth on the left side of hippocampus. It was registered a significant decrease in the NO content in hippocampus by 36 ± 17% on the 3rd day after modeling of hemorrhagic stroke together with decrease by an average of 24 ± 14% of the copper content. There were no significant changes in the NO level in hippocampus found neither on the 3rd day nor on the 7th day after brain injury modeling. There was also no change in copper content. Thus, it was experimentally demonstrated that modeling of brain injury, in contrast to hypoxia induced by hemorrhagic stroke, was not accompanied with significant changes in NO production in hippocampus of rat.

Objectives Cognitive decline is one of the most prevalent health problems and is associated with increased healthcare utilization and economic burden. Physical and cognitive training both have positive effects on cognition but have been less applied in combination. We hypothesized that simultaneous cognitive-physical components would yield greater cognitive benefits than single-domain interventions in rats. Methods A total of 40 male Wistar rats were divided into four treatment groups: the control, enriched environment (EE), exercise (EX), and EE + EX. Animals in EE groups housed in the large cages (50 × 50 × 50 cm) contained differently shaped objects for 3 weeks. EX animals were forced to run on a treadmill once daily for 3 consecutive weeks. Morris water maze test was used for the assessment of spatial learning and memory. Real-time PCR was performed to assess the expression of nestin, and Sox2 in the hippocampus. Results EX and EE animals separately did not show a significantly enhanced function in spatial memory in comparison with the control group. When animals were treated with EE and EX simultaneously, they exhibited significantly superior performance in spatial memory than control, EX, or EE groups separately. The hippocampal expression of Sox2 was significantly higher in EE + EX group than in the control, EX, and EE alone. Conclusions These results may have clinical implications for behavioral interventions in conditions with cognitive deficiencies.

The hippocampus, which has a central role in cognitive and behavioral activities, is one of the most sensitive parts of the brain to systemic inflammatory diseases. This animal study aims to comprehensively investigate the possible inflammatory, oxidative, and apoptotic effects of periodontitis on the hippocampus.Sixteen male Sprague-Dawley rats were randomly assigned to two groups: control and experimental periodontitis (Ep). In the Ep group, periodontitis was induced by placing 3.0 sutures sub-paramarginally around the necks of right and left mandibular first molars and maintaining the ligatures in place for 5 weeks. Following the euthanasia, mandibula and hippocampus samples were collected bilaterally. Alveolar bone loss was measured histomorphometrically and radiologically on the right and left mandibles. On the right hippocampal sections histological (Caspase-3, TNF-α, and 8-OHdG) and the left hippocampal sections, biochemical (IL-1β, AβHistopathological changes associated with periodontitis were limited (p .05). A slight increase in caspase-3 positive neuron density in EP rats showed that apoptotic changes were also limited (p .05). 8-OHdG activity, on the other hand, was significantly higher compared to controls (p .05). In biochemical analysis, there was a significant increase in IL-1β levels and oxidative membrane damage (MDA) (p .05) whereas AβPeriodontitis causes marked increases in IL-1β levels and oxidative stress in the hippocampus, but limited degenerative and apoptotic changes.

Background. The role of the transcriptional hypoxia-inducible factor-1α (Hif-1α) in the pathogenesis of hypoxic damage and diabetes mellitus (DM) is proved, although molecular mechanisms underlying dysfunction of this factor, when DM is combined with ischemic-reperfusion damage of the brain, remain unknown. The purpose was to study the content of Hif-1α protein in the hippocampal neurons of rats with experimental DM in the dynamics of ischemic-reperfusion damage of the brain. Materials and methods. The study was performed on 6-month-old rats with DM modeled by single administration of 60 mg/kg weight streptozotocin (Sigma, USA). The cerebrovascular disorders were reproduced by occlusion of both carotid arteries for 20 minutes. The content of Hif1-α protein was determined by immunofluorescence method after 20-minute ischemia with one-hour reperfusion, and on the 12th day of the post-ischemiс period in the fields CA1, CA2, CA3, and CA4 of the hippocampus. Results. In rats without DM, 20-minute ische­mia with one-hour reperfusion increases the content of Hif-1α protein in all the fields of the hippocampus. On the 12th day of ischemic-reperfusion period, the values of certain examined indices of transcriptional Hif-1α activity continue to increase in the hippocampal fields CA2-CA4, and in СА1 field they normalize or approach to the values of animals in the control group. In rats with DM during early post-ischemic period, there are no changes of Hif-1α protein content in CA1 field, in CA2 field there are signs of its reduced activity, in CA3 field they are limited by the reaction of one index, in CA4 field they are similar to those of the control rats under experimental conditions. On the 12th day of ischemic-reperfusion period, all the indices of transcriptional Hif-1α activity in CA1 field increase exceeding the corresponding indices in animals of the control group by absolute values under the same experimental conditions. In СА2 and СА3 fields, changes of the examined parameters are limited as compared to those in animals from the control group, in CA4 field, the values that were increased in the control group decrease. Conclusions. DM restricts the reaction of Hif-1α protein on ischemia-reperfusion in the neurons of СА1-СА3 fields in the early ischemic-reperfusion period and in the neurons of СА2-СА4 fields — on the 12th day of observation.

Background Electroconvulsive therapy (ECT) has been shown to induce broadly distributed cortical and subcortical volume increases, more prominently in the amygdala and the hippocampus. Structural changes after one ECT session and in the long-term have been understudied. Objective The aim of this study was to describe short-term and long-term volume changes induced in cortical and subcortical regions by ECT. Methods Structural brain data were acquired from depressed patients before and 2 h after their first ECT session, 7–14 days after the end of the ECT series and at 6 months follow up (N = 34). Healthy, age and gender matched volunteers were scanned according to the same schedule (N = 18) and patients affected by atrial fibrillation were scanned 1–2 h before and after undergoing electrical cardioversion (N = 16). Images were parcelled using FreeSurfer and estimates of cortical gray matter volume and subcortical volume changes were obtained using Quarc. Results Volume increase was observable in most of gray matter regions after 2 h from the first ECT session, with significant results in brain stem, bilateral hippocampi, right putamen and left thalamus, temporal and occipital regions in the right hemisphere. At the end of treatment series, widespread significant volume changes were observed. After six months, the right amygdala volume was still significantly increased. No significant changes were observed in the comparison groups. Conclusions Volume increases in gray matter areas can be detected 2 h after a single ECT session. Further studies are warranted to explore the underlying molecular mechanisms.

Neonatal hypoxic-ischaemic (HI) injury is a serious complication of neonatal asphyxia and the leading cause of neonatal acute death and chronic neurological injury, and the effective therapeutic method is lacking to improve patients' outcomes. We reported in this study that panax notoginseng saponin (PNS) may provide a treatment option for HI. HI model was established using neonatal Sprague-Dawley rats and then intraperitoneally injected with different dosage of PNS, once a day for 7 days. Histological staining and behavioural evaluations were performed to elucidate the pathological changes and neurobehavioural variation after PNS treatment. We found PNS administration significantly reduced the infarct volume of brain tissues and improved the autonomous activities of neonatal rats, especially with higher dosage. PNS treatment at 40 mg/kg reduced neuronal damage, suppressed neuronal apoptosis and depressed astroglial reactive response. Moreover, the long-term cognitive and motor functions were also improved after PNS treatment at 40 mg/kg. Importantly, PNS treatment elevated the levels of BDNF and TrkB but decreased the expression of p75NTR both in the cortex and hippocampus of HI rats. The therapeutic efficacy of PNS might be correlated with PNS-activated BDNF/TrkB signalling and inactivation of p75NTR expression, providing a novel potential therapy for alleviating HI injury.