ObjectiveTo investigate the effect of electroacupuncture on the apoptosis of hippocampal neurons in C57BL/6J mice with status epilepticus by observing the changes of hippocampal subtle neuron pathology and apoptosis.MethodsMale C57BL/6J mice were used to prepare epileptic status models of lithium-pilocarpine mice, and then 7-day electroacupuncture stimulation (Baihui, Fengfu) were given to the mice model. Open field experiment and new object recognition experiment were performed to observe the changes of cognitive abilities. The pathological changes of hippocampal neurons were detected by HE staining. Hippocampal apoptosis protein (Caspase-3) and microtubule-associated protein (MAP-2) were detected by immunohistochemistry. Effect of electroacupuncture on apoptosis of hippocampal neurons in C57BL/6J mice with status epilepticus were recorded.Results① Compared with the control group, the vertical movement, modification times, and number of crossings of the model group all decreased significantly (P<0.000 1,P<0.000 1,P<0.000 1), and their cognitive ability decreased significantly (P<0.01). Compared with the model group, vertical movements, modification times, and number of crossings were increased in the electroacupuncture (EA) group (P<0.01,P<0.05,P<0.05), and the cognitive ability of new objects was increased (P<0.01). ② HE staining showed that the model group had significant damage to the hippocampal neurons of mice, and the cells swelled, nuclear collapsed and vacuoles appeared. In the EA group, the injury of hippocampal neurons was alleviated, and cell edema and vacuolization were alleviated. ③ Immunohistochemistry showed that compared with the control group, the IOD of the Caspase-3 positive cells in the hippocampus of the model group increased significantly (P<0.000 1), and the IOD of the MAP-2 positive cells decreased significantly (P<0.01); Compared with the electroacupuncture, the IOD of the Caspase-3 positive cells in the hippocampus of the mice decreased (P<0.05), and the IOD of the MAP-2 positive cells increased (P<0.05).ConclusionsElectroacupuncture can improve the pathological changes of hippocampal neurons in C57BL/6J mice with status epilepticus, promote cytoskeletal repair, reduce neuronal apoptosis in hippocampus, and antagonize the damage of hippocampal neurons induced by status epilepticus.
ObjectiveTo observe the dynamic changes of neuroglobin (NGB) expression in hippocampus after status epilepticus(SE) in rats, and to explore the role of NGB in epileptic seizures.Methods40 healthy male Sprague Dawley rats were randomly divided into two group according to random number table method:control group (n=5) and epilepsy model group(n=35).Epilepsy model group according to observation time was divided into:0h, 1h, 3h, 12h, 24h, 10d and 30d.Intraperitoneal injection Lithium-pilocarpine (20 mg/kg~127 mg/kg, Li-PC) to establish the rat model of SE.Observe the behavioral changes in rats with epilepsy.Nissl staining was used to detect the neuronal damage in hippocampus. Streptavidin-biotin-peroxidase complex immunohistochemical method was used to detect the expression level of NGB in hippocampus;ResultsAfter SE, the neurons in hippocampus were severely damaged with the progress of epileptic seizures, the number of surviving neurons in CA1, CA3 regions showed a near linear decline.Among them, the number of surviving neurons in (12h, 24h, 10d, 30d)CA1, (0h, 12h, 24h, 10d, 30d)CA3 and(12h, 24h, 10d, 30d) DG area were significantly lower than that of the control group (P < 0.05).The expression level of NGB in CA1, CA3 and DG region of hippocampus were increased after SE, and both of CA1 and DG were reached peak in 24h after SE, but was still higher than the control group.And the CA3 area showed a continue rising trend.Among them, CA1(24h, 10d, 30d), CA3(24h, 10d, 30d) and DG(12h, 24h, 10d, 30d) were higher than that of control group significantly (P < 0.05).In addition, it was found that there was a positive correlation between the number of surviving neurons in CA3 area and the expression level of NGB (R=0.306, P=0.011).ConclusionUp-regulation of NGB expression in hippocampus after status epilepticus, and was positively correlated with the number of neurons in the CA3 area, suggesting that up regulation of NGB expression may be a compensatory protective mechanism of ischemic injury induced by seizures, and participate in the protection of epilepsy related neuronal damage.
ObjectiveTo study the differentially expressed proteins of recombinant human erythropoietin (r-HuEPO) in hippocampus of Pentetrazol (PTZ) -induced epileptic rats, and to provide a basis for exploring the pathogenesis of epilepsy and seeking new therapeutic targets. Methods Twelve 6~8-week-old Sprague Dawley rats that weighted 230~250 g were randomly divided into two groups: PTZ group, PTZ+ EPO group. The differential proteins of recombinant human EPO in hippocampus of pentylenetetrazole-induced epileptic rats were analyzed and identified by TMT technique based on mass spectrometry.Results 139 differentially expressed protein sites were detected in hippocampal tissues of epileptic rats, of which 55 were up-regulated and 84 down-regulated. Conclusion Recombinant human erythropoietin can inhibit many differentially expressed proteins in the hippocampus of pentaerythraze-induced eclampsia rats by upregulation of Isocitrate dehydrogenase (NADP), Reduced nicotinamide purine dinucleotide phosphate (NADPH), Thioredoxin reductase 2 mitochondrial (TrxR), reduce nerve cell damage.
Post-traumatic stress disorder (PTSD) is one of the common chronic diseases in psychiatry. It has a long course of disease which seriously affects patient’s life and work, and has a serious impact on social function. So far, the diagnosis of PTSD is limited to clinical symptom manifestations and physician experience, and no exact pathological substance basis is found, while the pathological substance basis is crucial for accurate diagnosis, selection of effective treatment methods, evaluation of treatment results, and assessment of disability. Head MRI is currently one of the most promising techniques to solve this problem. This paper reviews the progress in MRI research on brain structure changes in PTSD patients, in order to explore the possible future development directions.
ObjectiveTo investigate the effects of hippocampal long-term potentiation (LTP) on cognitive dysfunction in immature epileptic rats. MethodsImmature epileptic rats were established by intraperitoneal injection of lithium chloride-pilocarpine (li-pilo). Racine classification standard modified by Becker was used to evaluate behavior of epileptic seizure, and the survival rats within RacineⅣmagnitude were selected in the experiment. The function of learning and memory of epileptic rats when they were adult was assessed using Morris water maze experiment, and their independent exploratory behavior was evaluated by the open-field test. Field potential was recorded by electrophysiological technology to detecte whether hippocampal LTP was essential of cognitive dysfunction. ResultsThe function of learning and memory was significantly impaired when compared with controls(n=8, t=10.86, P < 0.05;n=8, t=9.98, P < 0.05). In addition, independent exploratory behavior was significantly reduced when compared with controls(n=8, t=12.89, P < 0.05). Besides, CA1 hippocampal LTP induced by high-frequency stimulation presented the significant inhibition in epileptic rats with cognitive dysfunction when compared with controls(Slope:n=8, t=13.32, P < 0.05;Amplitude:n=8, t=20.02, P < 0.05). ConclusionInhibition of CA1 hippocampal LTP may be implicated in cognitive dysfunction of epileptic rats.
The transmission and interaction of neural information between the hippocampus and the prefrontal cortex play an important role in learning and memory. However, the specific effects of learning memory-related tasks on the connectivity characteristics between these two brain regions remain inadequately understood. This study employed in vivo microelectrode recording to obtain local field potentials (LFPs) from the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) in eight rats during the performance of a T-maze task, assessed both before and after task learning. Additionally, dynamic causal modeling (DCM) was utilized to analyze alterations in causal connectivity between the vHPC and the mPFC during memory task execution pre- and post-learning. Results indicated the presence of forward connections from vHPC to mPFC and backward connections from mPFC to vHPC during the T-maze task. Moreover, the forward connection between these brain regions was slightly enhanced after task learning, whereas the backward connection was diminished. These changes in connectivity corresponded with the observed trends when the rats correctly performed the T-maze task. In conclusion, this study may facilitate future investigations into the underlying mechanisms of learning and memory from the perspective of connectivity characteristics between distinct brain regions.
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive impairment, with the predominant clinical diagnosis of spatial working memory (SWM) deficiency, which seriously affects the physical and mental health of patients. However, the current pharmacological therapies have unsatisfactory cure rates and other problems, so non-pharmacological physical therapies have gradually received widespread attention. Recently, a novel treatment using 40 Hz light flicker stimulation (40 Hz-LFS) to rescue the cognitive function of model animals with AD has made initial progress, but the neurophysiological mechanism remains unclear. Therefore, this paper will explore the potential neural mechanisms underlying the modulation of SWM by 40 Hz-LFS based on cross-frequency coupling (CFC). Ten adult Wistar rats were first subjected to acute LFS at frequencies of 20, 40, and 60 Hz. The entrainment effect of LFS with different frequency on neural oscillations in the hippocampus (HPC) and medial prefrontal cortex (mPFC) was analyzed. The results showed that acute 40 Hz-LFS was able to develop strong entrainment and significantly modulate the oscillation power of the low-frequency gamma (lγ) rhythms. The rats were then randomly divided into experimental and control groups of 5 rats each for a long-term 40 Hz-LFS (7 d). Their SWM function was assessed by a T-maze task, and the CFC changes in the HPC-mPFC circuit were analyzed by phase-amplitude coupling (PAC). The results showed that the behavioral performance of the experimental group was improved and the PAC of θ-lγ rhythm was enhanced, and the difference was statistically significant. The results of this paper suggested that the long-term 40 Hz-LFS effectively improved SWM function in rats, which may be attributed to its enhanced communication of different rhythmic oscillations in the relevant neural circuits. It is expected that the study in this paper will build a foundation for further research on the mechanism of 40 Hz-LFS to improve cognitive function and promote its clinical application in the future.
ObjectiveTo investigate the effect of dexamethasone on mammalian target of rapamycin (mTOR) expression of astrocytes in hippocampus of rats with sepsis associated encephalopathy (SAE). MethodsTotally, 90 cases of 30-day-old male Wistar rats were randomly divided into sham-operation group (n=10) and cecal ligation and puncture (CLP) group (n=80). Models of rats with sepsis were established by CLP. At 12 hours after CLP, if rats appeared lower neurobehavioral scores, abnormal electroencephalogram (EEG) and somatosensory evoked potential (SEP), they were diagnosed with SAE. And then, they were randomly divided into non-treated group and dexamethasone group. Rats in the dexamethasone group were injected with dexamethasone (1 mg/kg) via tail vein every other day for a total of 3 times. The same dose of saline was used in the non-treated group. The neurobehavioral score was measured, SEP and EEG were examined in the age of 40 days, and then the rats were killed and the hippocampus was taken. Expressions of mTOR protein were measured by Western blot. The glial fibrillary acidic protein (GFAP) and mTOR were detected by immunofluorescence assay, and the number of positive cells was calculated by image analysis system software. ResultsSix of 80 CLP rats died in 12 hours after operation, and 28 of 74 rats were diagnosed as SAE because they appeared lower neurobehavioral scores, abnormal EEG and SEP at 12 hours after CLP. The incidence of SAE was 37.84% (28/74). In the age of 40 days, compared with non-treated group, neurobehavioral score of rats in the dexamethasone group was low, the amount of alpha waves in EEG reduced, delta waves increased, the amplitude of P1 waves in SEP was decreased, and the latencies of P1 and N1 waves were prolonged (P＜0.05). GFAP immunofluorescence staining showed astrocytic body and processes were small in the sham operation group. However, astrocytes in the non-treated group had large body and hypertrophic processes, and compared with the sham operation group, the number of these cells increased significantly (P＜0.05). Astrocytic body and processes were small in the dexamethasone group compared with the non-treated group, and the number of cells also decreased (P＜0.05). The mTOR positive astrocytes in the non-treated group were more than those in the sham operation group (P＜0.05). But mTOR positive astrocytes in the dexamethasone group were fewer than those in the non-treated group (P＜0.05). ConclusionsAstrocytes are activated in the hippocampus of rats with SAE. They show features of reactive hyperplasia, and the expression of mTOR is up-regulated, while dexamethasone can inhibit effects on these.
ObjectiveTo explore the dynamic changes of microvessels in the hippocampal CA3 area in mice model of temporal lobe epilepsy (TLE) induced by pilocarpine. MethodsEighteen health SPF male C57BL/6 mice were randomly divided into control group and status epilepticus (SE) group. The SE group was subdivided into three groups:SE-7 days, SE-28 days and SE-56 days. SE was induced by intraperitoneal injection of pilocarpine. And immunohistochemical staining was used to detected the localization of platelet endothelial cell adhesion molecule-1 (PECAM-1). ResultsIn the control group, PECAM-1 labeled microvessels arranged in a layered structure, and the microvessel of the orient layer was most prominent. After SE, the microvessels started to form an unorganized vascular plexus and appeared fibrous and fragmented, which was prominent at SE-28 days. Furthermore, the microvessels density increased the top at SE-28 days compared to the control (P < 0.001). ConclusionThe angiogenesis exists during the hippocampus formation in the mice model of TLE induced by pilocarpine, which could direct a new explanation for TLE formation and development.
Epilepsy is a heterogeneous disease with a very complex etiological mechanism, characterized by recurrent and unpredictable abnormal neuronal discharge. Epilepsy patients mainly rely on oral antiseizure medication (ASMs) the for treatment and control of disease progression. However, about 30% patients are resistance to ASMs, leading to the inability to alleviate and cure seizures, which gradually evolve into refractory epilepsy. The most common type of intractable epilepsy is temporal lobe epilepsy. Therefore, in-depth exploration of the causes and molecular mechanisms of seizures is the key to find new methods for treating refractory epilepsy. Mitochondria are important organelles within cells, providing abundant energy to neurons and continuously driving their activity. Neurons rely on mitochondria for complex neurotransmitter transmission, synaptic plasticity processes, and the establishment of membrane excitability. The process by which the autophagy system degrades and metabolizes damaged mitochondria through lysosomes is called mitophagy. Mitophagy is a specific autophagic pathway that maintains cellular structure and function. Mitochondrial dysfunction can produce harmful reactive oxygen species, damage cell proteins and DNA, or trigger programmed cell death. Mitophagy helps maintain mitochondrial quality control and quantity regulation in various cell types, and is closely related to the occurrence and development of epilepsy. The imbalance of mitophagy regulation is one of the causes of abnormal neuronal discharge and epileptic seizures. Understanding its related mechanisms is crucial for the treatment and control of the progression of epilepsy in patients.