Number Of Hippocampal Neurons Research Articles

Long-term effects of pre-gestational stress and perinatal venlafaxine treatment on neurobehavioral development of female offspring

Preclinical studies suggest that stress-related disorders even prior gestation can cause long-term changes at the level of neurobehavioral adaptations. Therefore, it is critical to consider undergoing antidepressant therapy which could reverse the negative consequences in the offspring. Venlafaxine is widely used in clinical practice; however insufficient amount of well-controlled studies verified the safety of venlafaxine therapy during gestation and lactation. The aim of this work was to investigate the effects of perinatal venlafaxine therapy on selected neurobehavioral variables in mothers and their female offspring using a model of maternal adversity. Pre-gestational stressed and non-stressed Wistar rat dams were treated with either venlafaxine (10 mg/kg/day) or vehicle during pregnancy and lactation. We have shown that pre-gestational stress decreased the number of pups with a significant reduction in the number of males but not females. Furthermore, we found that offspring of stressed and treated mothers exhibited anxiogenic behavior in juvenile and adolescent age. However, during adulthood pre-gestational stress significantly increased anxiety-like behavior of female, with venlafaxine treatment normalizing the state to control levels. Additionally, we found that even maternal stress prior gestation can have long-term impact on adult number of hippocampal immature neurons of the female offspring. A number of questions related to the best treatment options for maternal depression still remains, however present data may provide greater insight into the possible outcomes associated with perinatal venlafaxine therapy.

Osthole Improves Cognitive Function of Vascular Dementia Rats: Reducing Aβ Deposition via Inhibition NLRP3 Inflammasome.

Vascular dementia (VD) is a common neurodegenerative disease, and the cognitive dysfunction is a major manifestation of VD. Lots of evidences showed that beta-amyloid (Aβ) deposition and neuroinflammation act as vital elements in the progress of VD. The previous studies showed that osthole (OST) can improve the cognitive function of VD and Alzheimer's disease (AD). However, the effect of OST on Aβ in VD brain is still unclear. Chronic cerebral hypoperfusion (CCH) of rats were used to investigate the effect of OST on Aβ through nod-like receptor protein 3 (NLRP3) inflammasome in this study. Morris Water Maze and Y-maze were used to test the spatial learning, memory and working abilities. Hematoxylin-eosin (H&E) and Nissl staining were used to observe the morphology and number of hippocampal neurons. Immunofluorescence staining was used to observe the number of microglia activated. Western blot was used to detect the expression of proteins. The study results showed that OST obviously enhanced the spatial learning, memory and working abilities induced by modified bilateral common carotid artery occlusion (BCCAO) in rats, improved the pathological damage of hippocampal neurons induced by BCCAO in rats, inhibited the activation of microglia induced by BCCAO in rats. Furthermore, this study also discovered that OST reduced Aβ deposition in VD hippocampus via inhibition the NLRP3 inflammasome. Together, these results suggest that OST reduces Aβ deposition via inhibition NLRP3 inflammasome in microglial in VD.

Altered mastication adversely impacts morpho-functional features of the hippocampus: A systematic review on animal studies in three different experimental conditionsinvolving the masticatory function.

Recent results have established that masticatory function plays a role not only in the balance of the stomatognathic system and in the central motor control, but also in the trophism of the hippocampus and in the cognitive activity. These implications have been shown in clinical studies and in animal researches as well, by means of histological, biochemical and behavioural techniques. This systematic review describes the effects of three forms of experimentally altered mastication, namely soft-diet feeding, molar extraction and bite-raising, on the trophism and function of the hippocampus in animal models. Through a systematic search of PubMed, Embase, Web of Science, Scopus, OpenGray and GrayMatters, 645 articles were identified, 33 full text articles were assessed for eligibility and 28 articles were included in the review process. The comprehensiveness of reporting was evaluated with the ARRIVE guidelines and the risk of bias with the SYRCLE RoB tool. The literature reviewed agrees that a disturbed mastication is significantly associated with a reduced number of hippocampal pyramidal neurons in Cornu Ammonis (CA)1 and CA3, downregulation of Brain Derived Neurotrophic Factor (BDNF), reduced synaptic activity, reduced neurogenesis in the Dentate Gyrus (DG), glial proliferation, and reduced performances in behavioural tests, indicating memory impairment and reduced spatial orientation. Moreover, while the bite-raised condition, characterized by occlusal instability, is known to be a source of stress, soft-diet feeding and molar extractions were not consistently associated with a stress response. More research is needed to clarify this topic. The emerging role of chewing in the preservation of hippocampal trophism, neurogenesis and synaptic activity is worthy of interest and may contribute to the study of neurodegenerative diseases in new and potentially relevant ways.

Salidroside shows anticonvulsant and neuroprotective effects by activating the Nrf2-ARE pathway in a pentylenetetrazol-kindling epileptic model

Evidence points towards oxidative stress and neuroinflammation being major processes associated with brain dysfunction in epilepsy. Salidroside reportedly possesses anti-oxidative activity and neuroprotective potential, in addition to exerting an anti-neuroinflammatory response. This study was designed to evaluate the anticonvulsant and neuroprotective role of salidroside in rats with pentylenetetrazole (PTZ) kindling and to explore the underlying mechanism. Male Wistar rats were administered a sub-convulsive dose of PTZ (35 mg/kg) every other day for 15 injections, and salidroside (50 mg/kg) was injected intraperitoneally along with alternate-day PTZ. The seizure degree, cognitive function, and number of hippocampal neurons were investigated. The expression of nuclear factor erythroid 2-related factor- antioxidant response element (Nrf2-ARE) signaling pathways, oxidative stress parameters and inflammatory cytokines were also observed. Our study showed that salidroside treatment suppressed the kindling acquisition process, ameliorated cognitive impairment, and rescued the number of pyramidal neurons in the CA3 regions. Salidroside treatment could activate the Nrf2-ARE signal pathway, and suppressed oxidative stress and neuroinflammation. Our findings demonstrated that salidroside exerted anticonvulsant and neuroprotective effects in epileptic rats by activating the Nrf2-ARE signal pathway.

Hippocampal volume and hippocampal neuron density, number and size in schizophrenia: a systematic review and meta-analysis of postmortem studies.

Reduced hippocampal volume is a consistent finding in neuroimaging studies of individuals with schizophrenia. While these studies have the advantage of large sample sizes, they are unable to quantify the cellular basis of structural or functional changes. In contrast, postmortem studies are well suited to explore subfield and cellular alterations, but low sample sizes and subject heterogeneity impede establishment of statistically significant differences. Here we use a meta-analytic approach to synthesize the extant literature of hippocampal subfield volume and cellular composition in schizophrenia patients and healthy control subjects. Following pre-registration (PROSPERO CRD42019138280), PubMed, Web of Science, and PsycINFO were searched using the term: (schizophrenia OR schizoaffective) AND (post-mortem OR postmortem) AND hippocampus. Subjects were adult men and women with schizophrenia or schizoaffective disorder or non-psychiatric control subjects, and key outcomes, stratified by hippocampal hemisphere and subfield, were volume, neuron number, neuron density, and neuron size. A random effects meta-analysis was performed. Thirty-two studies were included (413 patients, 415 controls). In patients, volume and neuron number were significantly reduced in multiple hippocampal subfields in left, but not right hippocampus, whereas neuron density was not significantly different in any hippocampal subfield. Neuron size, averaged bilaterally, was also significantly reduced in all calculated subfields. Heterogeneity was minimal to moderate, with rare evidence of publication bias. Meta-regression of age and illness duration did not explain heterogeneity of total hippocampal volume effect sizes. These results extend neuroimaging findings of smaller hippocampal volume in schizophrenia patients and further our understanding of regional and cellular neuropathology in schizophrenia.

Electroacupuncture Improves Cognition in Rats With Sepsis-Associated Encephalopathy

BackgroundSepsis-associated encephalopathy (SAE) is a common complication of sepsis. Although sepsis is effectively managed with the administration of antibiotics and source control, which may include surgical intervention, SAE usually leads to prolonged cognitive dysfunction affecting the quality of life of the patients. In this study, we investigated the possible effect of electroacupuncture (EA) on cognition in a model of SAE induced by cecal ligation and puncture (CLP). Materials and methodsThe rats were randomly divided into four groups: the control group, the CLP group, the CLP with EA treatment group (CLP + EA), and the CLP with sham EA treatment group (CLP + sham EA). EA at DU20, LI11, and ST36 or sham EA was performed 30 min daily for 10 consecutive days starting from 2 days before CLP. Then cognitive function was examined by the Morris water maze test. On day 14 after CLP surgery, the synaptic injury, neuron loss, and oxidative stress were studied. ResultsRats with EA treatment showed improved survival rate, spatial learning, and memory abilities. The dendritic spine density, the synaptic proteins, and the hippocampal neuron number were also increased after EA treatment. Furthermore, EA suppressed oxidative stress through regulating the level of malondialdehyde and superoxide dismutase and enhanced the expression of antioxidant nuclear factor erythroid-2–related factor-2 and hemeoxygenase-1. But sham EA did not have the same effect. ConclusionsEA may protect against SAE-induced cognitive dysfunction by inhibiting synaptic injury, neuronal loss, and oxidative stress, and the nuclear factor erythroid-2–related factor-2/hemeoxygenase-1 signaling pathway may be involved in this effect.

High intensity exercise increases brain derived neurotrophic factor expression and number of hippocampal neurons in rats

The decrease in brain derived neurotrophic factor (BDNF) expression and number of hippocampal neurons are two indicators in the decrease of memory function, cognitive, and learning function. The present study aimed to determine BDNF expression and the number of hippocampal neurons on moderate and high intensity exercise by listening to music. Design of the present study was a randomised control group post-test only design. A total of 33 male rats, Rattus norvegicus strain Wistar, aged eight weeks, with body weight 160±20 g were randomly divided into three groups: Group 1 (G1) (n=11, control group without intervention), Group 2 (G2) (n=11, performed moderate intensity exercise, treadmill 14-16 m/min for 30 min by listening to pop music with fast tempo of 160 beats/min) and Group 3 (G3) (n=11, high intensity exercise, treadmill 22-25 m/min for 20 min by listening to pop music with fast tempo of 160 beats/min). The intervention was performed between 17:00-21:00 pm, three times per week for 12 weeks. Blood and brain samples were obtained and evaluated 12 h after the end of the last exercise. BDNF serum was measured using ELISA and hippocampal neurons were stained by haematoxylin-eosin and counted using OlyVIA software. Study results showed a BDNF for G1 of 1,098.14±135.31 pg/ml, G2 of 1,113.72±65.87 pg/ml, and G3 of 1,331.56±105.35 pg/ml (P=0.001). The total number of hippocampal neurons for G1 was 54.75±6.83 cells, for G2 59.87±7.68 cells, and G3 80.58±9.79 cells (P=0.001). According to the study it can be concluded that high intensity exercise combined by listening to music with a fast tempo of 160 beats/min increases BDNF expression and the number of hippocampal neurons.

Preventing role of warmth-promotion needling in reducing intracellular Ca2＋ overload of in vitro hippocampal neuronal cells of vascular dementia rats

To investigate the underlying mechanisms of warming-promotion needling (WPN) for vascular dementia (VD) by observing its effect on the expression of L-type calcium channel current (Ica.L), changes of intracellular [Ca2＋]i in neurons and pathomorphological changes of brain in VD rats. One hundred and eight male SD rats were randomized into normal control, model, medication, WPN, uniform reinforcing-reducing needling (URRN), and needle-twirling groups (n＝18 in each group). The VD model was established by repeated occlusion and reperfusion of the bilateral common carotid arteries. Rats of the medication group were treated by gavage of Nimodipine twice a day for 14 days. For rats of the 3 acupuncture groups, WPN or URRN or needle-twirling was applied to "Dazhui" (GV14), "Baihui"(GV20) and "Shuigou"(GV26) for 30 min, once a day for 14 days. Changes of Ica.L in hippocampal neurons were observed by whole-cell patch clamp technique, and levels of [Ca2＋]i in neuronal cells of living brain slice of hippocampal CA1 area were observed by laser confocal microscope. Histopathological changes of hippocampal CA1 area were observed under light microscope after H．E. stain. Compared with the normal control group, the current density of Ica.L, and the intracellular[Ca2＋]i levels were significantly increased (P<0.05), and the I-V curves of Ica.L was apparently shifted down in the model group. In comparison with the model group, the current density of Ica.L was obviously reduced (P<0.05), the I-V curves of Ica.L shifted up and the intracellular Ca2＋ content notably decreased in the medication, WPN, URRN and needle-twirling groups (P<0.05). The effect of WPN was significantly superior to those of URRN and needle-twiiling (P<0.05). H．E. stain showed a reduction in the number of hippocampal neurons, dilation of intercellular space, swelling of cell body, karyopyknosis, disordered arrangement and increased number of gliacytes in the model group, which was apparently milder in the medication and 3 acupuncture groups (the WPN group in particular). The WPN can reduce Ica.L current density and [Ca2＋]i content of hippocampal neurons in brain slices of VD rats, which may contribute to its effect in relieving VD by suppressing calcium overload.

Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons.

Diabetes predisposes to cognitive decline leading to dementia and is associated with decreased brain NAD+ levels. This has triggered an intense interest in boosting nicotinamide adenine dinucleotide (NAD+) levels to prevent dementia. We tested if the administration of the precursor of NAD+, nicotinamide mononucleotide (NMN), can prevent diabetes-induced memory deficits. Diabetes was induced in Sprague-Dawley rats by the administration of streptozotocin (STZ). After 3 months of diabetes, hippocampal NAD+ levels were decreased (p = 0.011). In vivo localized high-resolution proton magnetic resonance spectroscopy (MRS) of the hippocampus showed an increase in the levels of glucose (p < 0.001), glutamate (p < 0.001), gamma aminobutyric acid (p = 0.018), myo-inositol (p = 0.018), and taurine (p < 0.001) and decreased levels of N-acetyl aspartate (p = 0.002) and glutathione (p < 0.001). There was a significant decrease in hippocampal CA1 neuronal volume (p < 0.001) and neuronal number (p < 0.001) in the Diabetic rats. Diabetic rats showed hippocampal related memory deficits. Intraperitoneal NMN (100 mg/kg) was given after induction and confirmation of diabetes and was provided on alternate days for 3 months. NMN increased brain NAD+ levels, normalized the levels of glutamate, taurine, N-acetyl aspartate (NAA), and glutathione. NMN-treatment prevented the loss of CA1 neurons and rescued the memory deficits despite having no significant effect on hyperglycemic or lipidemic control. In hippocampal protein extracts from Diabetic rats, SIRT1 and PGC-1α protein levels were decreased, and acetylation of proteins increased. NMN treatment prevented the diabetes-induced decrease in both SIRT1 and PGC-1α and promoted deacetylation of proteins. Our results indicate that NMN increased brain NAD+, activated the SIRT1 pathway, preserved mitochondrial oxidative phosphorylation (OXPHOS) function, prevented neuronal loss, and preserved cognition in Diabetic rats.

Matrix Metalloproteinase-9 Overexpression Regulates Hippocampal Synaptic Plasticity and Decreases Alcohol Consumption and Preference in Mice.

Brain matrix metalloproteinases (MMPs) have been recently implicated in alcohol addiction; however, the molecular mechanisms remain poorly understood. Matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease, is the best described MMP that is thought to regulate addictive behavior. In the present study, the effect of MMP-9 overexpression on hippocampal neuron plasticity and alcoholic behavior was assessed in spontaneous alcohol drinking mice. Two-bottle choice model showed that the overexpression of MMP-9 in the hippocampus developed by adeno-associated virus (AAV) could decrease alcohol consumption and preference, but did not affect taste preference, which was tested using saccharin or quinine solutions. Dendritic spines number of hippocampal neurons was observed by Golgi staining. Compared with the alcohol treatment group, the density of dendritic spines in the hippocampus of alcohol drinking mice was decreased in alcohol + MMP-9 group. Western blot analysis indicated that GluN1 expression in the hippocampus of alcohol drinking group was lower than that in the control group, while the expression of GluN1 was increased in MMP-9 overexpressing mice. MMP-9 also regulated the depolymerization of actin filaments, which induced behavioral changes in mice. Taken together, overexpression of MMP-9 in the hippocampal neurons of mice resulted in decreased dendritic spine density and F-actin/G-actin ratio, which might be the crucial reason for the significant decrease in alcohol consumption in alcohol drinking mice. MMP-9 might be considered as a novel target studying the molecular mechanism of alcohol drinking.

High-Fat-High-Fructose Diet Decreases Hippocampal Neuron Number in Male Rats

BACKGROUND: Consumption of foods and drinks high in energy, fat, and/or sugar beyond the recommended quantities can cause obesity, which triggers the incidence of brain nerve cell death related to oxidative stress, high levels of tumor necrosis factor (TNF)-α and triglycerides, and low high-density lipoprotein (HDL) levels. Progressive nerve cell death causes decreasing cognitive performance. This study aims to prove that an American Institute of Nutrition committee in 1993 (AIN-93M) diet modified with high-fat-high-fructose (HFHF) can decrease the number of hippocampal neurons. A decrease in the number of hippocampal neurons indicates progressive nerve cell death.METHODS: An experimental study using a post-test control group design was carried out using male Sprague Dawley rats. Samples were selected using simple random sampling to divide them into two groups, Group I was AIN-93M-modified HFHF diet (n=14) and Group II was AIN-93M standard (n=16). The number of visible neurons was measured in the hippocampus area of Sprague Dawley rats’ brains, stained with haemotoxylin and eosin (H&amp;E) and scanned under 400x magnification. Neurons were counted in 10 visual fields using the "Cell_Count" application.RESULTS: The data were analysed by Pearson’s correlation test using SPSS. The results show that rats in Group I had a greater weight gain and fewer neurons than those in the Group II (p=0.023, r=-0.413).CONCLUSION: The consumption of foods high in fat and fructose can cause an increase in nerve cell death, as shown by the decrease in the number of hippocampal neurons.KEYWORDS: brain nerve cells, high fat, high fructose, increased body weight

Electroacupuncture improved learning-memory ability by reducing hippocampal apoptosis and suppressing JNK signaling in rats with vascular dementia

To observe the effect of electroacupuncture (EA) stimulation on the expression of c-Jun terminal kinase(JNK)signaling pathway-related proteins in the hippocampus of vascular dementia (VD) rats, so as to explore its mechanisms underlying improvement of VD. Male Sprague-Dawley rats were randomly divided into sham operation, model and EA groups (n＝10 rats per group). The VD model was prepared by repeated occlusion of the bilateral common carotid arteries for 10 min and reperfusion for 10 min (3 times in total). The rats in the EA group received EA (2 Hz, 2 mA) at "Dazhui"(GV14)，"Baihui"(GV20), and bilateral "Housanli"(ST36) ，"Geshu"(BL17) for 10 min, once daily for 14 days. The learning-memory abi-lity was detected by Morris water maze tests, the distribution of hippocampal neurons detected by Nissl staining, and the apoptosis of hippocampal neurons detected by using TdT-mediated dUTP nick-end labeling (TUNEL) method. The expressions of JNK, phosphorylated JNK (p-JNK), cysteine-containing aspartate-specific proteases-8 (Caspase-8) and Caspase-3 proteins were detected by Western blot. After modeling and compared with the sham operation group, the escape latency was significantly prolonged (P<0.01) and the number of safe-platform quadrant crossing obviously decreased (P<0.01), suggesting a reduction of learning-memory ability. The number of hippocampal neurons was considerably reduced (P<0.01), and that of hippocampal apoptotic neurons remarkably increased in the model group (P<0.01). Whereas, the expression levels of hippocampal apoptosis-related proteins as JNK, p-JNK, Caspase-8 and Caspase-3, as well as the apoptotic index were significantly up-regulated (P<0.01). Following EA intervention, the learning-memory ability was apparently improved (P<0.01), and the number of hippocampal neurons was considerably increased (P<0.01), the hippocampal apoptotic cell number, apoptosis index and the expression levels of JNK, p-JNK, Caspase-8 and Caspase-3 were significantly down-regulated (P<0.01). EA intervention can improve the learning-memory ability of VD rats, which may be associated with its effects in reducing hippocampal apoptosis by suppressing JNK signaling pathway.

Involvement of homodomain interacting protein kinase 2-c-Jun N-terminal kinase/c-Jun cascade in the long-term synaptic toxicity and cognition impairment induced by neonatal Sevoflurane exposure.

Sevoflurane is one of the most widely used anesthetics with recent concerns rising about its pediatric application. The synaptic toxicity and mechanisms underlying its long‐term cognition impairment remain unclear. In this study, we investigated the expression and roles of homeodomain interacting protein kinase 2 (HIPK2), a stress activating kinase involved in neuronal survival and synaptic plasticity, and its downstream c‐Jun N‐terminal kinase (JNK)/c‐Jun signaling in the long‐term toxicity of neonatal Sevoflurane exposure. Our data showed that neonatal Sevoflurane exposure results in impairment of memory, enhancement of anxiety, less number of excitatory synapses and lower levels of synaptic proteins in the hippocampus of adult rats without significant changes of hippocampal neuron numbers. Up‐regulation of HIPK2 and JNK/c‐Jun was observed in hippocampal granular neurons shortly after Sevoflurane exposure and persisted to adult. 5‐((6‐Oxo‐5‐(6‐(piperazin‐1‐yl)pyridin‐3‐yl)‐1,6‐dihydropyridin‐3‐yl)methylene)thiazolidine‐2,4‐dione trifluoroacetate, antagonist of HIPK2, could significantly rescue the cognition impairment, decrease in long‐term potentiation, reduction in spine density and activation of JNK/c‐Jun induced by Sevoflurane. JNK antagonist SP600125 partially restored synapse development and cognitive function without affecting the expression of HIPK2. These data, in together, revealed a novel role of HIPK2‐JNK/c‐Jun signaling in the long‐term synaptic toxicity and cognition impairment of neonatal Sevoflurane exposure, indicating HIPK2‐JNK/c‐Jun cascade as a potential target for reducing the synaptic toxicity of Sevoflurane. Cover Image for this issue: doi: 10.1111/jnc.14757.

Low dosages of vitamin A may cause a decrease in the total neuron number of fetal hippocampal rat cells.

We investigated the effect of low, medium and high doses of oral vitamin A, on the number of fetal hippocampal neurons. High doses of vitamin A during pregnancy may cause embryonic malformations. There are reports about dosages that don't cause macroscopic malformations, but may cause mental and behavioral disorders. Still, quantitative morphological studies explaining this topic are lacking. We administered oral vitamin A to pregnant rats on the 10th-12th days of pregnancy at doses of 10000, 20000, 30000, 40000, 50000, 100000 and 200000 IU/kg. We collected the fetuses on the 19th day and removed their brains. After staining with cresyl violet and immunolabeling with Tunel and Ki67 antibody, we examined the hippocampi with stereological methods. Vitamin A decreased hippocampal neuron numbers beginning from 20000 IU/kg. While the number of Ki67 positive cells increased with the dosage, the increase of apoptotic cells begun at the dose of 50000 IU/kg. Our study demonstrates that vitamin A, beginning from the dosage of 20000 IU/kg, is decreasing the total hippocampal neuron numbers during the critical period of embryonic brain development and that apoptosis may not be the only factor in this outcome (Tab. 1, Fig. 3, Ref. 27).

Effects of Dexamethasone on Remodeling of the Hippocampal Synaptic Filamentous Actin Cytoskeleton in a Model of Pilocarpine-induced Status Epilepticus

The filamentous actin (F-actin) cytoskeleton is progressively damaged after status epilepticus (SE), which is related to delayed neuronal death, aberrant recurrent circuits and epileptogenesis. Glucocorticoids regulate dendritic spine remodeling by acting on glucocorticoid receptors and the dynamics of the F-actin cytoskeleton. Our previous study showed that administration of dexamethasone (DEX) in the latent period of the pilocarpine epileptic model reduces damage to the hippocampal filamentous actin cytoskeleton and the loss of hippocampal neurons and aids in maintaining the synaptic structures, but it is not sufficient to stop epileptogenesis. In this work, we focused on the role of glucocorticoids in regulating the hippocampal F-actin cytoskeleton during SE. We examined the abundance of synaptic F-actin, analyzed the hippocampal F-actin/G-actin (F/G) ratio and pCofilin, and evaluated the number of hippocampal neurons and pre/postsynaptic markers in pilocarpine-induced status epilepticus mice with or without administration of dexamethasone (DEX). We found that the latency of Stage 3 seizures increased, the mortality decreased, the damage to the synaptic F-actin cytoskeleton in the hippocampal subfields was significantly attenuated, and a greater number of postsynaptic structures were retained in the hippocampal subfields after treatment with DEX. These results indicate that treatment with dexamethasone stabilizes the synaptic F-actin cytoskeleton and reduces the damage to the brain due to SE. This approach is expected to be beneficial in alleviating delayed neuron damage and the process of epileptogenesis.

Dexamethasone impairs neurofunctional recovery in rats following traumatic brain injury by reducing circulating endothelial progenitor cells and angiogenesis

The administration of glucocorticoids (GCs) after traumatic brain injury (TBI) is controversial. Clinical evidence reveals the deleterious effects of GCs, but the mechanism remains unclear. Previous studies indicate that GCs impair wound healing by affecting endothelial progenitor cell (EPC) function and inhibiting angiogenesis after skin injury. Thus, we hypothesize that the central deleterious effect of GCs is associated with reduced EPCs and angiogenesis after TBI. Using a controlled cortical impact model, we examined the dynamic changes in circulating EPCs and in the regional microcirculation within 14 days of TBI by flow cytometry analysis and contrast-enhanced ultrasound, respectively. The modified neurological severity score (mNSS) and Morris water maze assay were used to assess neurological recovery. Angiogenesis and hippocampal neuron counts were assessed using immunohistochemistry analysis and hematoxylin and eosin staining 14 days after TBI. Compared with the TBI control group, dexamethasone treatment significantly reduced the number of circulating EPCs on days 1, 3, 7 and 14 (P < 0.05); decreased the number of CD31+ cells, the peak intensity and the number of hippocampal neurons on day 14 (P < 0.05); increased the latency on days 12 and 13 (P < 0.05); and reduced the percentage of time spent in the goal quadrant (P < 0.05) on day 14. Similarly, dexamethasone increased the mNSS on days 7 and 14 (P < 0.05). A strong correlation was observed between these results at 14 days after TBI (r = 0.815–0.892, P < 0.05). These data indicate that DEX inhibits the mobilization of EPC levels and angiogenesis around the lesion after TBI, which may contribute to neuronal cell loss and impaired neurofunction.

The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation

ObjectiveCerebral ischemia is the most common type of neuronal injury and is characterized by a reduction in the function and number of hippocampal neurons. Carvacrol has a significant neuroprotective effect in cerebral ischemia. However, the mechanisms by which carvacrol affects cerebral ischemia, especially with respect to the regulation of neuronal damage by iron levels, have never been systematically studied. This study aimed to reveal the mechanisms by which carvacrol protects against hippocampal neuron impairment after ischemic stroke in gerbils. Materials and methodsThe Morris water maze test was performed to evaluate learning and memory impairments. Iron ion content and oxidative stress index were detected by the kit. MTT assay was performed to assess the cell viability. The morphology and molecular characteristics were detected by electron micrographs and western blot. ResultsIn the present study, we demonstrated the neuroprotective effects of carvacrol in vivo and in vitro. The Morris water maze test showed that the learning and memory abilities of the gerbils treated with carvacrol were significantly improved. Lipid peroxide injury was evaluated by measuring the levels of lipid peroxide biomarkers; the results indicated that carvacrol decreased the level of lipid peroxide in ischemic gerbil brain tissue. Histopathological examinations and western blotting were performed to evaluate injury in neurons, and carvacrol reduced cell death. Moreover, ferroptosis in the hippocampus was evaluated by measuring the levels of proteins involved in this iron-dependent form of regulated cell death. These results indicated that carvacrol reduced cell death and that carvacrol inhibited ferroptosis by increasing the expression of glutathione peroxidase 4(GPx4). This study showed that carvacrol may be a valuable drug for treating cerebral ischemia. ConclusionCarvacrol provides protection for hippocampal neurons against I/R in gerbils by inhibiting ferroptosis through increasing the expression of GPx4.

Effect of cannabinoid receptor type 2 on the expression of autophagy-related proteins LC3 and Beclin-1 in the hippocampal CA1 region of rats with status epilepticus

Objective To explore effect of cannabinoid receptor type 2(CB2R)on the expression of autophagy-related proteins LC3 and Beclin-1 in the hippocampal CA1 region of rats with status epilepticus(SE). Methods SE model was established by treating lithium chloride-pilocarpine intraperitoneally injection in Sprague-Dawley(SD)rats.All the rats were randomly divided into four groups including Control group, Epilepsy group, Epilepsy+ JWH-133 group and Epilepsy+ AM630 group.JWH-133, AM630, and DMSO were injected 60 min before pilocarpine injection by intracerebroventricular injection(Control group and Epilepsy group with DMSO, Epilepsy+ JWH-133 group with JWH-133 and Epilepsy+ AM630 group with AM630). At 24 h after SE, the epileptic symptoms were observed.HE staining was performed to observe the number changes of neurons in the hippocampal CA1 region.The spatiotemporal expressions of LC3 and Beclin-1 in the hippocampal CA1 region were observed using Double-label immunofluorescence and Western blot. Results Epileptic symptoms showed that rats in the control group had no obvious epileptic seizures.Those in Epilepsy group presented seizures about (13.50±0.61)min after treated with pilocarpine and racine scale was (4.33±0.47) scores.The latency period in Epilepsy+ JWH-133 group was(19.33±0.42)min and longer than that in the Epilepsy group(P<0.05); Racine scale in Epilepsy+ JWH-133 group was 3.33±0.59 and less than the Epilepsy group(P<0.05). The opposite effect was observed in Epilepsy+ AM630 group.HE staining showed that compared with the Epilepsy group, the number of the hippocampal CA1 neurons increased in Epilepsy+ JWH-133 group and decreased in Epilepsy+ AM630 group.Immunofluorescence and Western blot showed that LC3 and Beclin-1 were mainly expressed in neurons, and the expression of LC3 and Beclin-1 in Epilepsy group were up-regulated dynamically than that in the control group at 24 h after SE(P<0.05). Furthermore compared with the Epilepsy group, the expression of LC3 and Beclin-1 in Epilepsy+ JWH-133 group were higher but lowered in Epilepsy+ AM630 group. Conclusion We demonstrate that CB2R may play a role in autophagy of the hippocampal neurons at the early stage of pilocarpine-induced SE and hinted CB2R may become a treatment target for epilepsy. Key words: Status epilepticus; Hippocampus; Cannabinoid receptor type 2; Autophagy; LC3; Beclin-1

Effects of ELK-1/JNK/c-Fos on apoptosis of rat hippocampal neurons cultured in vitro with Zuogui Jiangtang Jieyu Formula in simulated diabetes mellitus complicated with depression

To study the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF, the Chinese Medicine) on hippocampal neuron apoptosis in diabetes mellitus complicated with depression (DD). The primary cultured hippocampal neurons were treated with high glucose (150 mmol/L) and corticosterone (200 micromol/L) to establish the cell model of DD in vitro. The cultured hippocampal neurons were randomly divided into five groups: blank serum group, normal group, Zuogui Jiangtang Jieyu recipe drug-containing serum group, positive drug (metformin + fluoxetine) drug-containing serum group and model group (three compound holes in each group). The model group and the normal group were given the same amount of culture medium, and the other groups were given the corresponding serum with 10% volume fraction for 18 hours. Hoechst staining, high content cell imaging and RT-PCR were used to detect the apoptosis of hippocampal neurons and the expressions of apoptosis-related ETS-like 1 transcription factor(ELK-1), C-Jun N-terminal kinase(JNK) and c-Fos proteins and genes. Compared with the blank group, the apoptotic number of hippocampal neurons in the model group was increased significantly, and the expression levels of ELK-1, JNK and c-Fos were increased significantly (P＜0.05). Compared with the model group, the local bright spots of hippocampal neurons in the Zuogui Jiangtang Jieyu recipe-containing serum group and the positive drug-containing serum group were decreased significantly, and the number of apoptotic cells was decreased significantly. The expressions of JNK, c-fos protein and mRNA were down-regulated significantly (P＜ 0.05), and the neural network and dendritic junction were improved significantly. Zuo Gui Jiang Tang Jie Yu Formula can reverse the expressions of ELK-1, JNK and c-Fos signals in hippocampal neurons under DD environment and play an anti-apoptotic effect.

Propolis inhibited Bax expression and increased neuronal count of hippocampal area CA1 in rats receiving sodium nitrite

BackgroundSodium nitrite induces hypoxia and oxidative stress in the hippocampus, decreasing the number of neurons in the hippocampus and cognitive function. Propolis contains chrysin that has antioxidant effects that are expected to inhibit neuronal damage in the hippocampus. This study aims to determine the effects of propolis on the expression Bcl-2-associated X protein (Bax) and the number of neurons in the rat hippocampus receiving sodium nitrite.MethodsThis study of laboratory experimental design was conducted on 18 male Wistar strain rats (Rattus norvegicus), they were randomized into 3 groups: one control group (K) received sodium nitrite and two intervention groups (P1 and P2) received sodium nitrite and propolis at doses of 100 and 200 mg/kgBW. Treatment with sodium nitrite and propolis were given for 60 days, followed by termination. The number of neurons and Bax expression in the hippocampal CA1 area were measured. One-way ANOVA was used to analyze the data.ResultsThere were significant differences in Bax expression between group K and groups P1 and P2 (p&lt;0.001). The lowest number of neurons in the hippocampal CA1 area was in the K group. There were significant differences in the number of neurons between control (K) group and groups P1 and P2 (p&lt;0.001).ConclusionPropolis inhibited the expression of Bax and decreased the number of neurons in the hippocampal CA1 area of rats receiving sodium nitrite. This study provides information about the benefits of propolis as an antioxidant in the brain.