CA1 Region Of Rat Hippocampus Research Articles

Remifentanil pretreatment attenuates brain nerve injury in response to cardiopulmonary bypass by blocking AKT/NRF2 signal pathway

Objective This study aimed to explore the effect and mechanism of remifentanil on cardiopulmonary bypass (CPB)-induced cerebral nerve injury. Methods After pretreating with remifentanil, or dexmedetomidine (DEX), SD rats were subjected to the CPB for 2 h. The data of body temperature, blood gas and mean arterial pressure (MAP) and hematocrit (HCT) were recorded at different time points. The cerebral tissue water content of rats was determined and immunohistochemical (IHC) and H&E assays on the hippocampal CA1 region of rats was performed. The levels of interleukin (IL)-6, IL-10, soluble protein-100β (S100β) and neuron-specific enolase (NSE) were analyzed by ELISA, and those of the indexes for oxidative stress (malondialdehyde (MDA) and superoxide dismutase (SOD)) were detected by the commercial kits. Morris water maze was used to evaluate the learning and memory abilities. Western blot/qRT-PCR were used to detect the protein/mRNA expressions in hippocampus. Results CPB increased the levels/expressions of IL-6, IL-10, S100β, NSE, MDA, cleaved caspase-3, Bax and decreased those of Bcl-2, SOD, p-AKT, HO-1, in serum and parietal cortex tissue, with increased brain water content, lesions in the hippocampal CA1 area, swimming distance, brain nerve injury and decreased escape latency, retention time on platform and times of crossing the platform of rats. The preconditioning of remifentanil or DEX partially attenuated CPB-induced injury and -decreased expressions on p-AKT and HO-1, while further promoting CPB-induced expression of nuclear Nrf2 expression and inhibiting that of cytoplasm Nrf2. Conclusion This paper demonstrates that remifentanil preconditioning could partially attenuate CPB-induced brain nerve injury of rats.

Inhibition of NLRP3 inflammasome-mediated neuroinflammation alleviates electroconvulsive shock-induced memory impairment via regulation of hippocampal synaptic plasticity in depressive rats

Electroconvulsive shock has been considered one of the most effective treatment modalities for major depressive disorder. The association of acute transitory neuroinflammation in the hippocampus following electroconvulsive therapy with transient learning and memory impairment limits its clinical application. Whereas the NLRP3 inflammatory pathway is deemed to serve a key role in neuroinflammatory regulation, we aimed to examine if NLRP3 inflammasome activation was linked to electroconvulsive shock (ECS)-induced neuroinflammation and cognitive deficits. The depressed rats were modeled with chronic unpredictable mild stress. Their depression-like behaviors and cognitive performance were evaluated via sucrose preference test, forced swim test, open field test, and Morris water maze test. The NLRP3 expression was determined by western blot. The hippocampal CA1 region was immunohistochemically and electron-microscopically examined, respectively, for the activation of Iba-1 positive microglia and the ultrastructure of synapses. In this work, we found that ECS induced microglial activation in the rat hippocampal CA1 region. Pharmacological inhibition of NLRP3 inflammasome with MCC950 (NLRP3 inhibitor) in vivo significantly alleviated ECS-induced spatial learning and memory impairment, partially reversed neuroinflammation, and synaptic structural plasticity in the damaged hippocampal CA1 region, and reduced synapse associated protein expression and microglial activation. It offers a potential new approach for the prevention and treatment of cognitive decline following electroconvulsive therapy.

An Anodic Phase Can Facilitate Rather Than Weaken a Cathodic Phase to Activate Neurons in Biphasic-Pulse Axonal Stimulations.

Electrical pulses have been promisingly utilized in neural stimulations to treat various diseases. Usually, charge-balanced biphasic pulses are applied in the clinic to eliminate the possible side effects caused by charge accumulations. Because of its reversal action to the preceding cathodic phase, the subsequent anodic phase has been commonly considered to lower the activation efficiency of biphasic pulses. However, an anodic pulse itself can also activate axons with its “virtual cathode” effect. Therefore, we hypothesized that the anodic phase of a biphasic pulse could facilitate neuronal activation in some circumstances. To verify the hypothesis, we compared the activation efficiencies of cathodic pulse, biphasic pulse, and anodic pulse applied in both monopolar and bipolar modes in the axonal stimulation of alveus in rat hippocampal CA1 region in vivo. The antidromically evoked population spikes (APS) were recorded and used to evaluate the amount of integrated firing of pyramidal neurons induced by pulse stimulations. We also used a computational model to investigate the pulse effects on axons at various distances from the stimulation electrode. The experimental results showed that, with a small pulse intensity, a cathodic pulse recruited more neurons to fire than a biphasic pulse. However, the situation was reversed with an increased pulse intensity. In addition, setting an inter-phase gap of 100 μs was able to increase the activation efficiency of a biphasic pulse to exceed a cathodic pulse even with a relatively small pulse intensity. Furthermore, the latency of APS evoked by a cathodic pulse was always longer than that of APS evoked by a biphasic pulse, indicating different initial sites of the neuronal firing evoked by the different types of pulses. The computational results of axon modeling showed that the subsequent anodic phase was able to relieve the hyperpolarization block in the flanking regions generated by the preceding cathodic phase, thereby increasing rather than decreasing the activation efficiency of a biphasic pulse with a relatively great intensity. These results of both rat experiments and computational modeling firstly reveal a facilitation rather than an attenuation effect of the anodic phase on biphasic-pulse stimulations, which provides important information for designing electrical stimulations for neural therapies.

Cordycepin suppresses glutamatergic and GABAergic synaptic transmission through activation of A1 adenosine receptor in rat hippocampal CA1 pyramidal neurons.

Cordycepin (known as 3-deoxyadenosine, CRD), a natural product from the valuable traditional Chinese medicine Cordyceps militaris, has been reported to improve cognitive function and modulate neuroprotective effects on the central nervous system (CNS). However, the modulating mechanisms of cordycepin on information processing in hippocampal CA1 pyramidal neurons are not fully understood. To clarify how cordycepin modulates synaptic responses of pyramidal neurons in rat hippocampal CA1 region, we conducted an electrophysiological experiment using whole-cell patch-clamp technique. The spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs, respectively) and the spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs, respectively) recorded by this technique evaluated pure single or multi-synapse responses and enabled us to accurately quantify how cordycepin influenced the pre and postsynaptic aspects of synaptic transmission. The present results showed that cordycepin significantly decreased the frequency of both glutamatergic and GABAergic postsynaptic currents without affecting the amplitude, while these inhibitory effects were antagonized by the A1 adenosine receptor antagonist (DPCPX), but not the A2A (ZM 241385), A2B (MRS1754) and A3 (MRS1191) adenosine receptor antagonists. Taken together, our results suggested that cordycepin had a clear presynaptic effect on glutamatergic and GABAergic transmission, and provided novel evidence that cordycepin suppresses the synaptic transmission through the activation of A1AR.

Tamoxifen offers long-term neuroprotection after hippocampal silent infarct in male rats

Silent infarcts (SI) are a cerebral small vessel disease characterized by small subcortical infarcts. These occur in the absence of typical ischemia symptoms but are linked to cognitive decline and dementia. While there are no approved treatments for SI, recent results from our laboratory suggest that tamoxifen, a selective estrogen receptor modulator, is a viable candidate. In the present study, we induced SI in the dorsal hippocampal CA1 region of rats and assessed the effects of systemic administration of tamoxifen (5 mg/kg, twice) 21 days after injury on cognitive and pathophysiological measures, including cell loss, apoptosis, gliosis and estrogen receptors (ERs). We found that tamoxifen protected against the SI-induced cognitive dysfunction on the hippocampal-dependent, place recognition task, cell and ER loss, and increased apoptosis and gliosis in the CA1. Exploratory data analyses using a scatterplot matrix and principal component analysis indicated that SI-tamoxifen rats were indistinguishable from sham controls while they differed from SI rats, who were characterized by enhanced cell loss, apoptosis and gliosis, lower ERs, and recognition memory deficit. Supervised machine learning using support vector machine (SVM) determined predictors of progression from the early ischemic state to the dementia-like state. It showed that caspase-3 and ERα in the CA1 and exploration proportion were reliable and accurate predictors of this progression. Importantly, tamoxifen ameliorated SI-induced effects on all three of these variables, providing further evidence for its viability as a candidate treatment for SI and prevention of associated dementia.

Sulbactam improves binding property and uptake capacity of glutamate transporter-1 and decreases glutamate concentration in the CA1 region of hippocampus of global brain ischemic rats.

Glutamate transporter-1 (GLT-1) removes most glutamate in the synaptic cleft. Sulbactam confers neuronal protection against ischemic insults in the hippocampal CA1 region accompanied by the upregulation of GLT-1 expression in rats. The present study further investigates the effect of sulbactam on the binding property and uptake capacity of GLT-1 for glutamate, and the change in extracellular glutamate concentration in the hippocampal CA1 region of rats with global brain ischemia. The binding property and uptake capacity of GLT-1 were measured using a radioligand binding and uptake assay, respectively, with L-3H-glutamate. The extracellular glutamate concentration was detected using microdialysis and high-performance liquid chromatography-mass spectrometry. Neuropathological evaluation was performed based on thionin staining. It was shown that sulbactam pre-treatment changed GLT-1 binding property, including increased Bmax and decreased Kd values, increased GLT-1 uptake capacity for glutamate, and inhibited the elevation of extracellular glutamate concentration in rats with global cerebral ischemia. These effects of sulbactam were accompanied by its neuronal protection on the hippocampal CA1 neurons against delayed neuronal death resulted from ischemic insult. Furthermore, administration of GLT-1 antisense oligodeoxynucleotides, which inhibited the expression of GLT-1, blocked the aforementioned sulbactam-related effects, which suggested that GLT-1 upregulation mediated the above effect although other mechanisms independent of the upregulation of GLT-1 expression could not be excluded. It could be concluded that sulbactam improves the binding property and uptake capacity of GLT-1 for glutamate and then reduces the glutamate concentration and excitotoxicity during global cerebral ischemia, which contributes to the neuroprotection of sulbactam against brain ischemia.

Efficient spline regression for neural spiking data.

Point process generalized linear models (GLMs) provide a powerful tool for characterizing the coding properties of neural populations. Spline basis functions are often used in point process GLMs, when the relationship between the spiking and driving signals are nonlinear, but common choices for the structure of these spline bases often lead to loss of statistical power and numerical instability when the signals that influence spiking are bounded above or below. In particular, history dependent spike train models often suffer these issues at times immediately following a previous spike. This can make inferences related to refractoriness and bursting activity more challenging. Here, we propose a modified set of spline basis functions that assumes a flat derivative at the endpoints and show that this limits the uncertainty and numerical issues associated with cardinal splines. We illustrate the application of this modified basis to the problem of simultaneously estimating the place field and history dependent properties of a set of neurons from the CA1 region of rat hippocampus, and compare it with the other commonly used basis functions. We have made code available in MATLAB to implement spike train regression using these modified basis functions.

Spontaneous, transient adenosine release is not enhanced in the CA1 region of hippocampus during severe ischemia models.

Ischemic stroke causes damage in the brain, and a slow buildup of adenosine is neuroprotective during ischemic injury. Spontaneous, transient adenosine signaling, lasting only 3s per event, has been discovered that increases in frequency in the caudate-putamen during early stages of mild ischemia-reperfusion injury. However, spontaneous adenosine changes have not been studied in the hippocampus during ischemia, an area highly susceptible to stroke. Here, we investigated changes of spontaneous, transient adenosine in the CA1 region of rat hippocampus during three different models of the varied intensity of ischemia. During the early stages of the milder bilateral common carotid artery occlusion (BCCAO) model, there were fewer spontaneous, transient adenosine, but no change in the concentration of individual events. In contrast, during the moderate 2 vertebral artery occlusion (2VAO) and severe 4 vessel occlusion (4VO) models, both the frequency of spontaneous, transient adenosine and the average event adenosine concentration decreased. Blood flow measurements validate that the ischemia models decreased blood flow, and corresponding pathological changes were observed by transmission electron microscopy (TEM). 4VO occlusion showed the most severe damage in histology and BCCAO showed the least. Overall, our data suggest that there is no enhanced spontaneous adenosine release in the hippocampus during moderate and severe ischemia, which could be due to depletion of the rapidly releasable adenosine pool. Thus, during ischemic stroke, there are fewer spontaneous adenosine events that could inhibit neurotransmission, which might lead to more damage and less neuroprotection in the hippocampus CA1 region. Read the Editorial Highlight for this article on page 800.

Oxygen Enrichment Mitigates High-Altitude Hypoxia-Induced Hippocampal Neurodegeneration and Memory Dysfunction Associated with Attenuated Tau Phosphorylation.

Cai, Jing, Junyong Ruan, Xi Shao, Yuanjun Ding, Kangning Xie, Chi Tang, Zedong Yan, Erping Luo, and Da Jing. Oxygen enrichment mitigates high-altitude hypoxia-induced hippocampal neurodegeneration and memory dysfunction associated with attenuated tau phosphorylation. High Alt Med Biol. 22:274-284, 2021. Background: Brain is predominantly vulnerable to high-altitude hypoxia (HAH), resulting in neurodegeneration and cognitive impairment. The technology of oxygen enrichment has proven effective to decrease the heart rate and improve the arterial oxygen saturation by reducing the equivalent altitude. However, the efficacy of oxygen enrichment on HAH-induced cognitive impairments remains controversial based on the results of neuropsychological tests, and its role in HAH-induced hippocampal morphological and molecular changes remains unknown. Therefore, this study aims to systematically investigate the effects of oxygen enrichment on the memory dysfunction and hippocampal neurodegeneration caused by HAH. Materials and Methods: Fifty-one male Sprague-Dawley rats were equally assigned to three groups: normal control, HAH, and HAH with oxygen enrichment (HAHO). Rats in the HAH and HAHO groups were exposed to hypoxia for 3 days in a hypobaric hypoxia chamber at a simulated altitude of 6,000 m. Rats in the HAHO group were supplemented with oxygen-enriched air, with 12 hours/day in the hypobaric hypoxia chamber. Results: Our results showed that oxygen enrichment improved the locomotor activity of HAH-exposed rats. The Morris water maze test revealed that oxygen enrichment significantly ameliorated HAH-induced spatial memory deficits. Oxygen enrichment also improved morphological alterations of pyramidal cells and the ultrastructure of neurons in the hippocampal CA1 region in rats exposed to acute HAH. Tau hyperphosphorylation at Ser396, Ser262, Thr231, and Thr181 was also significantly attenuated by oxygen enrichment in HAH-exposed rats. Conclusions: Together, our study reveals that oxygen enrichment can ameliorate HAH-induced cognitive impairments associated with improved hippocampal morphology and molecular expression, and highlights that oxygen enrichment may become a promising alternative treatment against neurodegeneration for humans ascending to the plateau.

The p38 MAPK/NF-κB pathway mediates GLT-1 up-regulation during cerebral ischemic preconditioning-induced brain ischemic tolerance in rats

Our previous finding suggests that p38 MAPK contributes to the GLT-1 upregulation during induction of brain ischemic tolerance by cerebral ischemic preconditioning (CIP), however, the underlying mechanism is still unclear. Here, we investigated the molecular mechanisms underlying the CIP-induced GLT-1 upregulation by using Western blotting, Co-immunoprecipitation (Co-IP), electrophoretic mobility shift assay (EMSA) and thionin staining in rat hippocampus CA1 subset. We found that application of BAY11-7082 (an inhibitor of NF-κB), or dihydrokainate (an inhibitor of GLT-1), or SB203580 (an inhibitor of p38 MAPK) could attenuate the CIP-induced neuronal protection in hippocampus CA1 region of rats. Moreover, CIP caused rapid activation of NF-κB, as evidenced by nuclear translocation of NF-κB p50 protein, which led to active p50/p65 dimer formation and increased DNA binding activity. GLT-1 was also increased after CIP. Pretreatment with BAY11-7082 blocked the CIP-induced GLT-1 upregulation. The above results suggest that NF-κB participates in GLT-1 up-regulation during the induction of brain ischemic tolerance by CIP. We also found that pretreatment with SB203580 caused significant reduction of NF-κB p50 protein in nucleus, NF-κB p50/p65 dimer nuclear translocation and DNA binding activity of NF-κB. Together, we conclude that p38 MAPK/NF-κB pathway participates in the mediation of GLT-1 up-regulation during the induction of brain ischemic tolerance induced by CIP.

Enhanced expression of P2X4 purinoceptors in pyramidal neurons of the rat hippocampal CA1 region may be involved ischemia-reperfusion injury.

Ischemic stroke is the most serious disease that harms human beings. In principle, its treatment is to restore blood flow supply as soon as possible. However, after the blood flow is restored, it will lead to secondary brain injury, that is, ischemia-reperfusion injury. The mechanism of ischemia-reperfusion injury is very complicated. This study showed that P2X4 receptors in the pyramidal neurons of rat hippocampus were significantly upregulated in the early stage of ischemia-reperfusion injury. Neurons with high expression of P2X4 receptors are neurons that are undergoing apoptosis. Intraventricular injection of the P2X4 receptor antagonist 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD) and PSB-12062 can partially block neuronal apoptosis, to promote the survival of neurons, indicating that ATP through P2X4 receptors is involved in the process of cerebral ischemia-reperfusion injury. Therefore, identifying the mechanism of neuronal degeneration induced by extracellular ATP via P2X4 receptors after ischemia-reperfusion will likely find new targets for the treatment of ischemia-reperfusion injury, and will provide a useful theoretical basis for the treatment of ischemia-reperfusion injury.

Different effects of monophasic pulses and biphasic pulses applied by a bipolar stimulation electrode in the rat hippocampal CA1 region

BackgroundElectrical pulse stimulations have been applied in brain for treating certain diseases such as movement disorders. High-frequency stimulations (HFS) of biphasic pulses have been used in clinic stimulations, such as deep brain stimulation (DBS), to minimize the risk of tissue damages caused by the electrical stimulations. However, HFS sequences of monophasic pulses have often been used in animal experiments for studying neuronal responses to the stimulations. It is not clear yet what the differences of the neuronal responses to the HFS of monophasic pulses from the HFS of biphasic pulses are.MethodsTo investigate the neuronal responses to the two types of pulses, orthodromic-HFS (O-HFS) and antidromic-HFS (A-HFS) of biphasic and monophasic pulses (1-min) were delivered by bipolar electrodes, respectively, to the Schaffer collaterals (i.e., afferent fibers) and the alveus fibers (i.e., efferent fibers) of the rat hippocampal CA1 region in vivo. Evoked population spikes of CA1 pyramidal neurons to the HFSs were recorded in the CA1 region. In addition, single pulses of antidromic- and orthodromic-test stimuli were applied before and after HFSs to evaluate the baseline and the recovery of neuronal activity, respectively.ResultsSpreading depression (SD) appeared during sequences of 200-Hz monophasic O-HFS with a high incidence (4/5), but did not appear during corresponding 200-Hz biphasic O-HFS (0/6). A preceding burst of population spikes appeared before the SD waveforms. Then, the SD propagated slowly, silenced neuronal firing temporarily and resulted in partial recovery of orthodromically evoked population spikes (OPS) after the end of O-HFS. No SD events appeared during the O-HFS with a lower frequency of 100 Hz of monophasic or biphasic pulses (0/5 and 0/6, respectively), neither during the A-HFS of 200-Hz pulses (0/9). The antidromically evoked population spikes (APS) after 200-Hz biphasic A-HFS recovered to baseline level within ~ 2 min. However, the APS only recovered partially after the 200-Hz A-HFS of monophasic pulses.ConclusionsThe O-HFS with a higher frequency of monophasic pulses can induce the abnormal neuron activity of SD and the A-HFS of monophasic pulses can cause a persisting attenuation of neuronal excitability, indicating neuronal damages caused by monophasic stimulations in brain tissues. The results provide guidance for proper stimulation protocols in clinic and animal experiments.

The effects of gastrin-releasing peptide on the voltage-gated channels in rat hippocampal neurons

Gastrin-releasing peptide (GRP) has been implicated in several aspects of physiology and behavior including digestion, cancer, lung development, and memory process. Increasing evidence in rodents shows that GRP may contribute to hippocampal circuit function. Though the central role of GRP in the brain has been established, the cellular and molecular mechanisms of its actions have not been well defined. Thus in this study, we verified the expression of GRPR in the rat hippocampal CA1 region. Then we examined the mechanisms closely related to neuronal excitability, the effects of GRP on voltage-gated ion channels in CA1 neurons using patch-clamp. The results showed that GRP could decrease voltage-gated sodium currents mainly by affecting the kinetics of recovery from the inactivated state. However, GRP enhanced both kinds of voltage-gated potassium channels, the A-type channels were more sensitive to GRP than K-type channels. In conclusion, we found that GRP could alter the voltage-gated Na+ and K+ ion channel characteristics which might be the ionic mechanisms of the physiological function of GRP in the brain.

T-type Ca2+ channel activity increases in rat hippocampal CA1 region during kindling epileptogenesis.

Epileptogenesis is a dynamical process that involves synaptic plasticity changes such as synaptic reorganization of excitatory and inhibitory systems and axonal sprouting in the hippocampus, which is one of the most studied epileptogenic regions in the brain. However, the early events that trigger these changes are not understood well. We investigated short-term and long-term synaptic plasticity parameters and T-type Ca2+ channel activity changes in the early phase of a rat kindling model. Chronic pentylenetetrazole (PTZ) application was used in order to induce the kindling process in rats. The recordings were obtained from hippocampal slices in the CA1 region at 25th day of PTZ application. Tetraethylammonium was used in order to induce long-term potentiation and T-type Ca2+ channel activity was assessed in the presence of mibefradil. We found that tetraethylammonium-induced long-term potentiation was not prevented by mibefradil in the kindling group in contrast to control group. We also found an increase in paired-pulse ratios in the PTZ-applied group. Our findings indicate an increase in the "T-type Ca2+ channel component of LTP" in the kindling group, which may be an early mechanism in epileptogenesis.

Dexmedetomidine Exerts Brain-Protective Effects Under Cardiopulmonary Bypass Through Inhibiting the Janus Kinase 2/Signal Transducers and Activators of Transcription 3 Pathway.

Brain injury is a major complication resulted from cardiopulmonary bypass (CPB). Dexmedetomidine (DEX) has potential brain-protective effects; however, the mechanism is unclear. The aim of this study is to investigate the effect of DEX on brain injury in CPB rats and its mechanism. The levels of interleukin-6 (IL-6), interleukin-10 (IL-10), S100β, and neuron-specific enolase (NSE) were measured by enzyme-linked immunosorbent assay. The hippocampus CA1 region in rats was observed by hematoxylin-eosin staining. Western blot and quantitative real-time polymerase chain reaction were performed to detect related proteins and mRNA expressions in the hippocampus tissues. We found that after CPB, the neuron cells in hippocampus CA1 region of rats were randomly arranged, and that the levels of IL-6, IL-10, S100β, NSE, Cleaved Caspase-3, and Bax were upregulated, while Bal-2 level was downregulated. However, after DEX treatment, the neuron cells arranged in an orderly manner, and the levels of IL-6, IL-10, S100β, NSE, Cleaved Caspase-3, and Bax were downregulated, but Bal-2 level was upregulated. DEX suppressed Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathway activated by CPB, ameliorated CPB-induced brain injury in rats by reducing inflammatory response, and inhibited neuronal apoptosis. The brain-protective effect of DEX may be related to the inhibition of the activation of JAK2/STAT3 pathway.

Amiodarone does not affect brain injury in a rat model of transient forebrain ischemia

ObjectivesAlthough amiodarone may cause neurotoxicity that can affect patient outcomes when used during cardiopulmonary resuscitation (CPR), it has been commonly prescribed during CPR. This study investigated the possible neurotoxic effects of amiodarone in a rat model of transient forebrain ischemia. DesignA prospective laboratory animal study was carried out. SettingAnimal laboratory. MaterialsMale Sprague-Dawley rats. InterventionEight minutes of forebrain ischemia was induced in rats by bilateral carotid occlusion and hypotension (mean arterial pressure=35mmHg) under isoflurane (1.5%) anesthesia. Amiodarone (0, 50, 100 and 150mg/kg) with saline was injected intraperitoneally 10min after ischemia. Rats given 0mg/kg of amiodarone were used as saline-treated controls. Sham operated rats received no treatment. Variables of interestAnimals were evaluated neurologically on postoperative days 4–7, and histologically after a one-week recovery period. ResultsThe greatest improvement in water maze test performance corresponded to the sham operated group (p=0.015 vs. saline-treated controls). No differences in performance were seen in amiodarone-treated rats compared with saline-treated controls. In the control group, 45% of the CA1 hippocampal neurons survived, compared with 78% in the sham operated group (p=0.009). Neuron survival after ischemia in the amiodarone treatment groups (50, 100 and 150mg/kg) (58%, 40% and 36%, respectively) and in the control rats did not differ significantly. ConclusionsThe administration of amiodarone immediately after transient forebrain ischemia did not worsen spatial cognitive function or neuronal survival in the hippocampal CA1 region in rats. The current results must be applied with caution in humans. However, they indicate that the potential neurotoxicity induced by amiodarone during resuscitation after cardiac arrest may be negligible.

Toxicological evaluation of the nicotine on CA1 and protective effects of curcuma longa: An experimental study

Introduction: Nicotine is the most important alkaloid compound in tobacco and is a major risk factor in the development of functional disorders of several organ systems. Some plants produce Curcuma longa (curcumin), which has antioxidant and neuro-protective properties.
 Methods: This study was designed to evaluate the therapeutic effects of curcumin against nicotine injury on the hippocampus CA1 region of rats. In this study, 48 male rats were randomly assigned to eight groups: Normal control (saline) group, Nicotine control group (0.5 mg/kg); Curcumin groups (10, 30, and 60 mg/kg) and Nicotine + Curcumin groups (10, 30, and 60 mg/kg). Treatments were administered intra-peritoneally daily for 28 days. Golgi staining technique investigated the number of dendritic spines. Cresyl violet staining method was used to determine the number of neurons in the hippocampal region CA1. Griess technique was assessed to determine serum nitrite oxide levels. Also, the ferric reducing/antioxidant power (FRAP) method was applied to determine the total antioxidant capacity.
 Results: Nicotine administration significantly increased the nitrite oxide level and decreased total antioxidant capacity. The number of neuronal dendritic spines, as well as neurons per se, also decreased, compared to the control group (p < 0.01). In all the members of the Curcumin and Nicotine + Curcumin groups, the number of neurons, neuronal dendritic spines and total antioxidant capacity increased significantly compared to the nicotine control group, while nitrite oxide level decreased significantly compared to the nicotine control group (p < 0.01).
 Conclusions: It seems that Curcumin administration improved hippocampal CA1 region injury in rats caused by Nicotine.

Effect of curcumin on hippocampus dentate gyrus injury induced by nicotine in rats

Introduction: Nicotine is the most important alkaloid compound in tobacco and is a major risk factor in the development of functional disorder of several organ systems. Some plants produce Curcumin, which has antioxidant and neuroprotective properties. This study was designed to evaluate the therapeutic effects of curcumin against nicotine injury on the hippocampus CA1 region of rats. Methods: In this study, 48 male Wistar rats were randomly assigned to eight groups: Normal control (saline) group, Nicotine control group (0.5 mg/kg); Curcumin groups (10, 30, and 60 mg/kg) and Nicotine + Curcumin groups (10, 30, and 60 mg/kg). Treatments were administered intraperitoneally daily for 28 days. Golgi staining technique investigated the number of dendritic spines. Cresyl violet staining method was used to determine the number of neurons in hippocampal region CA1. Griess technique was assessed to determine serum nitrite oxide level. Also, the Ferric reducing/antioxidant power (FRAP) method was applied to determine the total antioxidant capacity. Results: Nicotine administration significantly increased nitrite oxide level and decreased total antioxidant capacity as well as the number of neuronal dendritic spines and neurons compared to the normal control group (P < 0.01). In all Curcumin and Nicotine + Curcumin groups, the number of neurons, neuronal dendritic spines, and total antioxidant capacity increased significantly compared to the nicotine control group, while nitrite oxide level decreased significantly compared to the nicotine control group (P < 0.01). Conclusion: Curcumin administration can improve hippocampal CA1 region injury induced by nicotine.

Effects of exposure to extremely low frequency electromagnetic fields on hippocampal long-term potentiation in hippocampal CA1 region

Exposure to environmental electromagnetic fields, especially to the extremely low-frequency (ELF < 300 Hz) electromagnetic fields (EMFs) might produce modulation effects on neuronal activity. Long-term changes in synaptic plasticity such as long-term potentiation (LTP) involved in learning and memory may have contributions to a number of neurological diseases. However, the modulation effects of ELF-EMFs on LTP are not yet fully understood. In our present study, we aimed to evaluate the effects of exposure to ELF-EMFs on LTP in hippocampal CA1 region in rats. Hippocampal slices were exposed to magnetic fields generated by sXcELF system with different frequencies (15, 50, and 100 Hz [Hz]), intensities (0.5, 1, and 2 mT [mT]), and duration (10 s [s], 20 s, 40 s, 60 s, and 5 min), then the baseline signal recordings for 20 min and the evoked field excitatory postsynaptic potentials (fEPSPs) were recorded. We found that the LTP amplitudes decreased after magnetic field exposure, and the LTP amplitudes decreased in proportion to exposure doses and durations, suggesting ELF-EMFs may have dose and duration-dependent inhibition effects. Among multiple exposure duration and doses combinations, upon 5 min magnetic field exposure, 15 Hz/2 mT maximally inhibited LTP. Under 15 Hz/2 mT ELF-EMFs, LTP amplitude decreases in proportion to the length of exposure durations within 5 min time frame. Our findings illustrated the potential effects of ELF-EMFs on synaptic plasticity and will lead to better understanding of the influence on learning and memory.

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