Mitochondrial transplantation ameliorates hippocampal damage following status epilepticus

Background:Hippocampal damage caused by status epilepticus(SE)can bring about cognitive decline and emotional disorders,which are common clinical comorbidities in patients with epilepsy.It is therefore imperative to develop a novel therapeutic strat-egy for protecting hippocampal damage after SE.Mitochondrial dysfunction is one of contributing factors in epilepsy.Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria,we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE.Methods:Pilocarpine was used to induced SE in mice.SE-generated cognitive de-cline and emotional disorders were determined using novel object recognition,the tail suspension test,and the open field test.SE-induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes.The metabolites underlying mitochondrial transplantation were determined using metabonomics.Results:The results showed that peripheral administration of isolated mitochon-dria could improve cognitive deficits and depressive and anxiety-like behaviors.Exogenous mitochondria blunted the production of reactive oxygen species,pro-liferation of microglia and astrocytes,and loss of neurons in the hippocampus.The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism.Among potential affected metabolites,mitochondrial transplantation decreased levels of sphingolipid(d18:1/18:0)and methylmalonic acid,and elevated levels of D-fructose-1,6-bisphosphate.Conclusion:To the best of our knowledge,these findings provide the first direct ex-perimental evidence that artificial mitochondrial transplantation is capable of amelio-rating hippocampal damage following SE.These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy-associated psychiat-ric and cognitive disorders.

Activation of metabotropic glutamate receptor 1 regulates hippocampal CA1 region excitability in rats with status epilepticus by suppressing the HCN1 channel

Dysregulation of hyperpolarization-activated cyclic nucleotide-gated cation(HCN)channels alters neuronal excitability.However,the role of HCN channels in status epilepticus is not fully understood.In this study,we established rat models of pentylenetetrazole-induced status epilepticus.We performed western blot assays and immunofluorescence staining.Our results showed that HCN1 channel protein expression,particularly HCN1 surface protein,was significantly decreased in the hippocampal CA1 region,whereas the expression of HCN2 channel protein was unchanged.Moreover,metabolic glutamate receptor 1(mGluR1)protein expression was increased after status epilepticus.The mGluR1 agonist(RS)-3,5-dihydroxyphenylglycine injected intracerebroventricularly increased the sensitivity and severity of pentylenetetrazole-induced status epilepticus,whereas application of the mGluR1 antagonist(+)-2-methyl-4-carboxyphenylglycine(LY367385)alleviated the severity of pentylenetetrazole-induced status epilepticus.The results from double immunofluorescence labeling revealed that mGluR1 and HCN1 were co-localized in the CA1 region.Subsequently,a protein kinase A inhibitor(H89)administered intraperitoneally successfully reversed HCN1 channel inhibition,thereby suppressing the severity and prolonging the latency of pentylenetetrazole-induced status epilepticus.Furthermore,H89 reduced the level of mGluR1,downregulated cyclic adenosine monophosphate(cAMP)/protein kinase A expression,significantly increased tetratricopeptide repeat-containing Rab8b-interacting protein(TRIP8b)(1a-4)expression,and restored TRIP8b(1b-2)levels.TRIP8b(1a-4)and TRIP8b(1b-2)are subunits of Rab8b interacting protein that regulate HCN1 surface protein.

Ocimum sanctum extract preserves neuronal echotexture and controls seizure in lithium-pilocarpine induced status epilepticus rats

Objective:To investigate the effect of Ocimum sanctum hydroalcoholic extract(OSHE)on seizure control and neuronal injury in rats with lithium-pilocarpine-induced status epilepticus(SE).Methods:SE was induced by administering lithium chloride followed by pilocarpine 24 h later.OSHE was administered either alone or in combination with valproate(VPA)3 days before SE induction until 14 days post-SE induction.Seizure parameters were recorded on day 1(0-3 h),day 1-3 and day 4-14 post-SE.On day 14 post-SE,neurobehavioural tests(elevated plus maze and passive avoidance)were done followed by total antioxidant capacity,neuron-specific enolase,immunohistochemistry,and electron microscopic assessment in the hippocampus and cortex tissue.Results:OSHE+VPA provided more significant seizure protection(75%)than VPA(62.5%),OSHE(62.5%),or SE control(12.5%)(overall P=0.003).The latency to stage-3/4 seizures was increased and the number of stage-3/4 seizures was reduced in all treatment groups compared to the SE control group(P=0.002 and<0.001,respectively).The OSHE+VPA group also had better memory retention than other treatment groups(P<0.001)in the passive avoidance test.Total antioxidant capacity level was significantly higher and neuron-specific enolase was lower in the OSHE and OSHE+VPA groups compared to the SE control group.Electron microscopic study showed significant myelin sheath damage(67.5%,P<0.05)and axonal degeneration(51.8%,P<0.001)in the hippocampus of the SE control group,which were alleviated by OSHE or OSHE+VPA treatment.In immunohistochemical analysis,the OSHE,OSHE+VPA,and VPA groups had a significantly higher number of viable neurons and less neuronal loss compared to the SE control in the hippocampus(P<0.001).Conclusions:OSHE either alone or in combination with VPA shows better seizure control by preservation of neuronal echotexture and reducing oxidative stress in the hippocampus.

Hippocampus protection from apoptosis by Baicalin in a LiClpilocarpine-induced rat status epilepticus model through autophagy activation

BACKGROUND Autophagy is associated with hippocampal injury following status epilepticus(SE)and is considered a potential therapeutic mechanism.Baicalin,an emerging multitherapeutic drug,has shown neuroprotective effects in patients with nervous system diseases due to its antioxidant properties.AIM To investigate the potential role of autophagy in LiCl-pilocarpine-induced SE.METHODS The drugs were administered 30 min before SE.Nissl staining showed that Baicalin attenuated hippocampal injury and reduced neuronal death in the hippocampus.Western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling assay confirmed that Baicalin reversed the expression intensity of cleaved caspase-3 and apoptosis in hippocampal CA1 following SE.Furthermore,western blotting and immunofluorescence staining were used to measure the expression of autophagy markers(p62/SQSTM1,Beclin 1,and LC3)and apoptotic pathway markers(cleaved caspase-3 and Bcl-2).RESULTS Baicalin significantly upregulated autophagic activity and downregulated mitochondrial apoptotic pathway markers.Conversely,3-methyladenine,a commonly used autophagy inhibitor,was simultaneously administered to inhibit the Baicalin-induced autophagy,abrogating the protective effect of Baicalin on the mitochondrial apoptotic level.CONCLUSION We illustrated that Baicalin-induced activation of autophagy alleviates apoptotic death and protects the hippocampus of SE rats.

Non Convulsive Status Epilepticus: An Elusive Diagnosis

Absence status is the most common form of non-convulsive status epilepticus and is characterized by confusion with varying degrees of memory loss and cognitive impairment. Patients and Method: Three children were sent to neurological consultation due to behavioral alterations and a prolonged confused state;they were hospitalized and treated with sodium diphenylhydantoinate (DPH) IV at a dose of 10 mg/Kg. Results: The duration of symptoms varied from 6 months to 10 days. All three patients presented with global mental alterations, showing slowness in response and action. The electroencephalogram showed a pattern of slow, generalized stem and poly-stem-wavelengths of 3 - 4 Hz, which were registered for one hour. After the DPH bolus, the attack spontaneously ended in the 3 patients and upon examination all three presented with amnesia of the events occurring during the attack. In the follow-up, two of the patients did not experience further episodes and they showed normal scholastic achievement. The third patient however, after suffering a 6-month status epilepticus, failed the school year and finished his elementary education until the age of 15, experiencing similar difficulties with his secondary education. Discussion: Non-convulsive status epilepticus is more difficult to diagnose mainly because the manifestations are predominantly psychiatric and can be confused with other diseases or with an overdose of anti- convulsive drugs. A prolonged state of mental confusion, with no other explanation, should alert the attending physician to take an electroencephalogram in order to confirm the diagnosis. In our patients, DPH immediately controlled paroxysmal activity. We can therefore conclude that the problem is not in the treatment, but rather in making the correct diagnosis.

Propofol effectively inhibits lithium-pilocarpine-induced status epilepticus in rats via downregulation of N-methyl-D-aspartate receptor 2B subunit expression

Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine.The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior,electroencephalography and 24-hour survival rate.Propofol（12.5-100 mg/kg） improved status epilepticus in a dose-dependent manner,and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection.Western blot results showed that,24 hours after induction of status epilepticus,the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus.Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels,but not the increase in N-methyl-D-aspartate receptor 2A subunit levels.The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine.This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures.

Effects of ethanol extracts of scorpion on hippocampal apoptosis and caspase-3 expression in lithium chloride-pilocarpine-induced status epilepticus rats

BACKGROUND： Previous studies have demonstrated that scorpion venom in the scorpion can inhibit epilepsy and apoptosis. However, it remains unclear whether ethanol extracts of scorpion （EES） exhibit similar effects. OBJECTIVE： To investigate the effects of EES on hippocampal apoptosis and caspase-3 expression, and to compare the effects on sodium valproate （positive control drug） in a rat model of status epilepticus induced by lithium chloride-pilocarpine. DESIGN, TIME AND SETTING： This randomized, controlled study was conducted at the Drug Research and Development Center, Kanghong Pharmaceuticals Group, and the Department of Pathology, Sichuan Academy of Medical Sciences ＆ Sichuan Provincial People＇s Hospital, China from May 2007 to April 2008. MATERIALS： EES were prepared by Huashen Pharmaceutical, China. Sodium valproate （Hunan Xiangzhong Pharmaceutical, China） and lithium chloride-pilocarpine （Sigma, USA） were also used in the present study. METHODS： From a total of 156 rats, six served as normal controls. The remaining rats were intraperitoneally injected with lithium chloride-pilocarpine to establish status epileptlcus models, and then assigned to five groups （n = 30, respectively）. Animals in each group were administered drugs at 15 minutes after epileptic seizure by gavage, i.e. in the normal control and model groups, rats were treated with 1 mL/0.1 kg saline. The sodium valproate group was administered 120 mg/kg/d sodium valproate. The low-, moderate-, and high-dose EES groups received treatments of 290, 580 and 1 160 mg/kg/d EES. The dispensed concentration was 1 mL/0.1 kg. Rat seizure behavior was observed. If status epilepticus did not terminated after 1 hour, the rats were intraperitoneally administered atropine （1 mg/kg） and diazepam （10 mg/kg） to terminate seizure. These rats were continuously observed for 6 hours to ensure seizure termination. Then rats were treated with the above-mentioned drugs at 8：00 am each day until sacrifice, which took place 4 hours after drug administration. MAIN OUTCOME MEASURES： Terminal dUTP nick end labeling （TUNEL）-positive cells and caspase-3 expression were, respectively, determined by TUNEL and immunohistochemistry at 6, 24 48, and 72 hours, as well as 7 days, after status epilepticus. Behavioral changes were also measured. RESULTS： A few caspase-3-positive cells were observed. TUNEL- and caspase-3-positive ceils were mainly visible in the hippocampal CA1 and CA3 regions 6 hours following status epilepticus in the model and drug intervention groups. The number of TUNEL-positive cells reached a peak at 48 hours following status epilepticus in the sodium valproate group, as well as the moderate- and high-dose EES groups, and number of TUNEL-positive cells reached a peak at 72 hours in the model and low-dose EES groups. The number of caspase-3-positive cells reached a peak at 48 hours in each group. Following treatment of sodium valproate and EES, the number of TUNEL- and caspase-3-positive cells significantly decreased compared with the model group at various time points （P 〈 0.05）. The number of TUNEL- and caspase-3-positive cells was greatest in the low-dose EES group, followed by the moderate- and high-dose EES groups. The number of TUNEL- and caspase-3-positive cells was similar between the sodium valproate and high-dose EES groups. Epileptic seizure was significantly improved in the sodium valproate group, as well as the moderate- and high-dose EES groups, compared with the model group （P〈 0.05 or P〈 0.01）. Treatment with sodium valproate and high-dose EES resulted in the best outcome, although the results were similar （P 〉 0.05）. CONCLUSION： A dose of 1 160 mg/kg/d EES significantly inhibited status epilepticus. This outcome corresponded to a decreased number of apoptotlc cells and caspase-3-positive cells, which was similar to sodium valproate. These results suggest that it is not necessary to extract a component from the scorpion for the treatment of epilepsy. The high dose of EES significantly inhibited epilepsy, which correlated with decreased hippocampal caspase-3 expression.

Mitochondrial and nuclear changes in hippocampal neurons in a lithium-pilocarpine-induced status epilepticus rat model

BACKGROUND： Mitochondrial damage plays a key role in neuronal damage. OBJECTIVE： To observe ultrastructural damage to mitochondria and nuclei, as well as caspase-3 expression, in hippocampal CA3 neurons of lithium-pilocarpine-induced status epilepticus rats. DESIGN, TIME AND SETTING： The neuropathological, randomized, controlled study was performed at the Animal Experimental Center, Shandong University, China in May 2008. MATERIALS： A total of 75 healthy, adult, male, Wistar rats were randomly assigned into model （n = 45） and control （n = 30） groups. Lithium-pilocarpine （Sigma, USA） was used in this study. METHODS： Rats in the model group were intraperitoneally injected with lithium chloride （3 mEq/kg）, and 24 hours later with pilocarpine （45 mg/kg）, to induce seizures for 2 hours. Rats in the control group were intraperitoneally infused with the same volume of saline. Rat hippocampal CA3 tissue was obtained at 3, 12, and 24 hours following status epilepticus. MAIN OUTCOME MEASURES： Neuronal changes were observed under an optical microscope. Ultrastructural changes in mitochondria and nuclei were observed using an electron microscope. caspase-3 mRNA levels were quantified by semiquantitative RT-PCR. RESULTS： After 3 hours of status epilepticus, mitochondria with swollen cristae and ruptured membranes were observed by electron microscopy. Nuclei with marginated chromatin were observed after 24 hours status epilepticus. RT-PCR results demonstrated increased caspase-3 expression at 12 hours, and significantly increased expression at 24 hours following termination of status epilepticus. This was in accordance with acidophilia occurrence, as indicated by hematoxylin-eosin staining, and time of ultrastructural damage to nuclei. CONCLUSION： In lithium-pilocarpine-induced status epilepticus rat models, ultrastructural damage to mitochondria in hippocampal neurons occurred during early stages, followed by increased caspase-3 expression and nuclear changes. These results suggested that mitochondrial damage plays a key role in neuronal damage following status epilepticus.

Dynamic expression of P-glycoprotein in the CA1,CA3 and dentate gyrus of the rat hippocampus following lithium-pilocarpine-induced status epilepticus

Epileptic seizures induce overexpression of P-glycoprotein in the blood-brain barrier. However, it is unclear whether hippocampal neurons also overexpress P-glycoprotein following seizure. This study confirmed that the clinical manifestation, pathological characteristics and electroencephalography in the rat model of lithium-pilocarpine-induced mesial temporal lobe epilepsy were consistent with clinical reports of mesial temporal lobe epilepsy in humans.Immunohistochemistry staining demonstrated that P-glycoprotein positive staining was found in neurons in the pyramidal layer of the hippocampus. Westem blot assay and real-time polymerase chain reaction revealed that P-glycoprotein overexpression was exhibited in the CA1, CA3, and dentate gyrus of the hippocampus at 24 and 60 days following model induction, but no significant dffierence was detected in the same region at various time points. These results indicate that seizures led to overexpression of P-glycoprotein in neurons of the hippocampus, but no evidence was found for a positive association between P-glycoprotein expression and seizure frequency.

Status epilepticus as a complication after COVID-19 mRNA-1273 vaccine:A case report

BACKGROUND We present a rare case of status epilepticus in a 56-year-old man which arose as a complication after vaccination with the coronavirus disease 2019(COVID-19)mRNA-1273 vaccine.The patient's history included well-compensated secondary epilepsy.The root cause of the situation was a fever which had developed as a side effect of the vaccination.CASE SUMMARY A 56-year-old man received the first dose of mRNA-1273 vaccine against the severe acute respiratory syndrome-coronavirus-2.The vaccine was administered intramuscularly(100 mg,0.5 mL).The next morning the man was found to be suffering from fever and headaches while at the same time experiencing general weakness.He lost consciousness suddenly and experienced generalized clonic seizures which turned into status epilepticus.When the Emergency Medical Service arrived the patient was unconscious with spontaneous breathing and generalized clonic seizures.It was necessary to administer diazepam repeatedly.It was also necessary to administer high doses of levetiracetam and temporary propofol.The status epilepticus was brought under control approximately 90 min after the patient’s transport to the Emergency Department.A follow-up electroencephalogram no longer revealed abnormal indications of epileptic fit.The patient was temporarily hospitalized in the Intensive Care Unit and after seven days care was discharged without any further apparent effects.CONCLUSION There is currently no specific treatment against COVID-19.Therefore,the benefits of COVID-19 vaccine protection outweigh the risks.

Status epilepticus as an initial manifestation of hepatic encephalopathy:A case report

BACKGROUND Status epilepticus in patients with hepatic encephalopathy (HE) is a rare butserious condition that is refractory to antiepileptic drugs, and current treatmentplans are vague. Diagnosis may be difficult without a clear history of cirrhosis.Liver transplantation (LT) is effective to alleviate symptoms, however, there arefew reports about LT in the treatment of status epilepticus with HE. To ourknowledge, this is the first report of status epilepticus present as initialmanifestation of HE.CASE SUMMARY A 59-year-old woman with a 20-year history of heavy drinking was hospitalizedfor generalized tonic-clonic seizures. She reported no history of episodes of HE,stroke, spontaneous bacterial peritonitis, ascites or gastrointestinal bleeding.Neurological examination revealed a comatose patient, without papilledema.Laboratory examination suggested liver cirrhosis. Plasma ammonia levels uponadmission were five times normal. Brain computed tomography (CT) was normal,while abdominal CT and ultrasound revealed mild ascites, liver cirrhosis andsplenomegaly. Electroencephalography (EEG)showed diffuse slow waves rhythm,consistent with HE, and sharp waves during ictal EEG corresponding to clinicalsemiology of focal tonic seizures. The symptoms were reversed by continuousantiepileptic treatment and lactulose. She was given oral levetiracetam, and focalaware seizures occasionally affected her 10 mo after LT.CONCLUSION Status epilepticus could be an initial manifestation of HE. Antiepileptic drugs combined with lactulose are essential for treatment of status epilepticus with HE,and LT is effective to prevent the relapse.

Status epilepticus increases mature granule cells in the molecular layer of the dentate gyrus in rats

Enhanced neurogenesis in the dentate gyrus of the hippocampus following seizure activity, especially status epilepticus, is associated with ectopic residence and aberrant integration of newborn granule cells. Hilar ectopic granule cells may be detrimental to the stability of dentate circuitry by means of their electrophysiological properties and synaptic connectivity. We hypothesized that status epilepticus also increases ectopic granule cells in the molecular layer. Status epilepticus was induced in male Sprague-Dawley rats by intraperitoneal injection of pilocarpine. Immunostaining showed that many doublecortin-positive cells were present in the molecular layer and the hilus 7 days after the induction of status epilepticus. At least 10 weeks after status epilepticus, the estimated number of cells positive for both prospero homeobox protein 1 and neuron-specific nuclear protein in the hilus was significantly increased. A similar trend was also found in the molecular layer. These findings indicate that status epilepticus can increase the numbers of mature and ectopic newborn granule cells in the molecular layer.

Alterative application of five anticonvulsants according to the half life for the treatment of status epilepticus in children with severe viral encephalitis

BACKGROUND： Traditional subhibernation therapy may easily cause complications, such as respiratory depression and hyportension because of application of chlorpromazine hydrochloride and promethazine in a large dosage. OBJECTIVE： To observe therapeutic effect of modified subhibernation therapy （alterative application of five anticonvulsants according to the half life） on status epilepticus in children with severe viral encephalitis （VE）. DESIGN： Contrast observation. SETTING： Department of Pediatrics, the First Hospital of Jilin University. PARTICIPANTS： The participants in present study were 96 patients with severe viral encephalitis including 52 boys and 44 girls who received treatment in the Department of Pediatrics, the First Hospital of Jilin University from February 2000 to March 2006. All children met the diagnostic criteria of Zhufutong Practice Pediatrics （the seventh edition）. Two weeks ago, they ever got upper respiratory infection or enteronitis and so on before the onset, spirit abnormal, behavior disorder, limbs act disorder, vomit, headache, convulsion, nervous system masculine signs such as limbs act disord, autonomic nerve damage manifestation, brain nerve palsy, dysreflexia, meningeal irritation sign, cerebrospinal fluid and electroencephalography （EEG） abnormity. All parents provided the confirmed consent. The patients were randomly divided into control group （n =40） and experimental group （n =56）. METHODS： Patients in the control group received anticonvulsion, ice compress and routine treatment. The convulsion was treated with five drugs： 0.5 mg/kg wintermin and phenergan, respectively, 100 g/L chlorpromazine hydrochloride （0.5 mL/kg）, 5 mg/kg luminal, 0.3 mg/kg ansiolin. When convulsion attacked, those five drugs were given alternatively; however, those were not given if the convulsion did not attack. Children in the experimental group were treated with improved subhibernation therapy based on routine treatment. The dosages of anticonvulsants were as the same as those in the control group. Based on the half life, every drug was alternated every 4-6 hours. In addition, anticonvulsants administrated for 2 successive days whether tic attacked or not. Then the hypnotic was removed gradually. MAIN OUTCOME MEASURES： Therapeutic efficacy, time of disappeared clinical symptoms and physical sign, and security of administration. RESULTS： All the 96 patients were involved in the final analysis. ① Total effective rate and reliability： Total effective rate was higher in the treatment groups than the control group （χ2=5.871 7, P 〈 0.05）. All patients did not have respiratory depression and side effects. ② Time of disappeared clinical symptoms and physical sign： Recovery time of convulsion, fever, headache and vomit was shorter in the treatment group than that in the control group, and there was significant difference （t =17.612 1-34.330 7, P 〈 0.05）; in addition, symptoms of status epilepticus were relieved obviously. Meanwhile, recovery time of paralysis, coma and anepia was shorter in the treatment group than that in the control group, and there was significant difference （t =10.660 8-24.700 8, P 〈 0.05）. CONCLUSION： Therapeutic effect of improved subhibernation therapy on status epilepticus induced by severe viral encephalitis is positively and safer.

癫痫持续状态(Status epilepticus)的治疗

治疗原则1.控制抽搐发作。2.防止并发症的发生并根据病情变化,作适宜的对症处理。3.查出病因,尽早施行病因治疗。

Cinnamon Attenuates Cognitive Dysfunction,Hippocampal Oxidative Stress and Neurodegeneration Following Status Epilepticus in Young Male Rats

The present study explores the neuroprotective effects of the natural food product Cinnamomum cassia or Cinnamon(CIN)on lithium pilocarpine(Li-Pc)induced SE in experimental rats to look into a possibility of it being used as antiepileptic drug.Recent studies have shown significant potential of pharmacological,prophylactic or therapeutic use of CIN in many beneficial activities in the body.The animals received CIN pre-treatment before induction of SE.Besides the severity of the seizures,other parameters like cognitive behavioral dysfunction,hippocampal oxidative stress and histological abnormalities in the hippocampus of animals induced with SE by lithium(Li)in 3 mEq/ml/kg dose,i.p.followed 20 h later by pilocarpine(Pc)in 20 mg/ml/kg dose,s.c.CIN was administered intraperitoneally at the doses of 25 and 50 mg/mL/kg,30 minutes before Pc injection.Mortality(if any)within 24 hours was also recorded.Ethical approval was obtained from the Ethics Committee Review Board of the College of Pharmacy of King Saud University,Riyadh,Saudi Arabia.Treatment with CIN significantly ameliorated the frequency and severity of epileptic seizures in a dose-dependent manner.The cognitive dysfunctions were improved,hippocampal oxidative stress was ameliorated and neuronal cell loss in the hippocampus were also attenuated significantly and dose-dependently by CIN.Possible therapeutic application of CIN as an antiepileptic and as an antioxidant for the treatment of SE has a great potential and warrants further studies.

Status Epilepticus and Coma in Pregnancy. Management Dilemma in a Resource Limited Setting (Monatele, Cameroon): Case Report

Epilepsy is a leading neurological condition characterized by recurrent seizures and affecting more than 50 million people worldwide. Status epilepticus (SE) is a neurological emergency associated with a high mortality rate and long-term cognitive sequelae. In pregnancy, status epilepticus poses a tremendous threat to both mother and fetus. We report a case of status epilepticus in pregnancy complicated by coma, where obstetrical ultrasound revealed fetal demise in utero followed by rapid maternal deterioration and demise later. There was management challenge of a comatose pregnant mother in very poor and deteriorating hemodynamic state with fetal demise in a low economic and limited resource setting.

Cytokines in new-onset refractory status epilepticus:ready for clinical use?

New-onset refractory status epilepticus(NORSE)is a rare and challenging condition characterized by refractory status epilepticus in an otherwise healthy patient without obvious causes.Increasing evidence suggests a change in cytokine profiles in NORSE.However,the clinical utility of cytokine testing remains uncertain,primarily because of the lack of robust study designs and limited sample sizes.A recent study published in Annals of Neurology investigated the cytokine profiles in both serum and cerebrospinal fluid samples of NORSE patients.The study found elevated levels of CXCL8,CCL2,and MIP-1αin the serum and elevated levels of IL-1ßin the cerebrospinal fluid of NORSE patients compared to those with other forms of refractory status epilepticus(RSE).Furthermore,patients with cryptogenic NORSE had even higher levels of CXCL8,CCL2,and MIP-1αin the serum.Patients with NORSE who exhibited elevated levels of innate immunity cytokines in the serum had worse outcomes at discharge and several months after the NORSE ended.In summary,these findings highlight the association between inflammation-related cytokines and NORSE,providing new insights into clinical diagnosis and treatment approaches.

Status epilepticus in patients with genetic generalized epilepsy:a case series study

Background Genetic generalized epilepsy(GGE)accounts for nearly one-third of all epilepsies.The feature of status epilepticus(SE)in patients with GGE has been rarely studied.We aimed to determine the electroclinical characteristics of SEin patients with GGE.Methods In this retrospective study,nine patients with GGE were enrolled at Xijing Hospital,Xi'an,China from May 2014 to May 2020.SE was confrmed by 24-h video-EEG recording.The demography,clinical manifestation,brain MRI and SEpatternwereanalyzed.Results Of the nine patients in the study,seven were female.The mean age of the patients at the time of inclusion was 16.8 years(range 7-31 years),and the mean age at the onset of epilepsy was 10.9 years(range 6-17 years).The follow-up time ranged from 3 months to 6 years.Myoclonic absence status was identified in four patients showing eyelid myoclonia with absence and one patient showing perioral myoclonia with absences.Myoclonic SE was identi-fied in three patients showing juvenile myoclonic epilepsy.Autonomic SE was found in one patient with eyelid myo-clonia with absence.SE was terminated by oral midazolam in four patients.In the other five patients,SE terminated spontaneously.Conclusions The seizure type of SE in patients with GGE is often consistent with their major symptoms.Oral mida-zolam may be an option to terminate SE in patients with GGE.

Early Hypothermia for Refractory Status Epilepticus

INTRODUCTION Currently, the recommended therapy to control refractory status epilepticus （RSE） is intravenous （IV） anesthetics, such as midazolam, propofol, barbiturates, and so on. However, 15%-26% of RSE cases still cannot be terminated.

Characterization of the Expression of the ATP-Gated P2X7 Receptor Following Status Epilepticus and during Epilepsy Using a P2X7-EGFP Reporter Mouse

Mounting evidence suggests that the ATP-gated P2X7 receptor contributes to increased hyperexcitability in the brain.While increased expression of P2X7 in the hippocampus and cortex following status epilepticus and during epilepsy has been repeatedly demonstrated,the cell type-specific expression of P2X7 and its expression in extra-hippocampal brain structures remains incompletely explored.In this study,P2X7 expression was visualized by using a transgenic mouse model overexpressing P2X7 fused to the fluorescent protein EGFP.The results showed increased P2X7-EGFP expression after status epilepticus induced by intra-amygdala kainic acid and during epilepsy in different brain regions including the hippocampus,cortex,striatum,thalamus and cerebellum,and this was most evident in microglia and oligodendrocytes.Colocalization of P2X7-EGFP with cell type-specific markers was not detected in neurons or astrocytes.These data suggest that P2X7 activation is a common pathological hallmark across different brain structures,possibly contributing to brain inflammation and neurodegeneration following acute seizures and during epilepsy.