A drug-loaded flexible substrate improves the performance of conformal cortical electrodes

Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.

The generation and properties of human cortical organoids as a disease model for malformations of cortical development

As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.

MET receptor tyrosine kinase promotes the generation of functional synapses in adult cortical circuits

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

Cortical activity in patients with high-functioning ischemic stroke during the Purdue Pegboard Test:insights into bimanual coordinated fine motor skills with functional near-infrared spectroscopy

After stroke,even high-functioning individuals may experience compromised bimanual coordination and fine motor dexterity,leading to reduced functional independence.Bilateral arm training has been proposed as a promising intervention to address these deficits.However,the neural basis of the impairment of functional fine motor skills and their relationship to bimanual coordination performance in stroke patients remains unclear,limiting the development of more targeted interventions.To address this gap,our study employed functional near-infrared spectroscopy to investigate cortical responses in patients after stroke as they perform functional tasks that engage fine motor control and coordination.Twenty-four high-functioning patients with ischemic stroke(7 women,17 men;mean age 64.75±10.84 years)participated in this cross-sectional observational study and completed four subtasks from the Purdue Pegboard Test,which measures unimanual and bimanual finger and hand dexterity.We found significant bilateral activation of the sensorimotor cortices during all Purdue Pegboard Test subtasks,with bimanual tasks inducing higher cortical activation than the assembly subtask.Importantly,patients with better bimanual coordination exhibited lower cortical activation during the other three Purdue Pegboard Test subtasks.Notably,the observed neural response patterns varied depending on the specific subtask.In the unaffected hand task,the differences were primarily observed in the ipsilesional hemisphere.In contrast,the bilateral sensorimotor cortices and the contralesional hemisphere played a more prominent role in the bimanual task and assembly task,respectively.While significant correlations were found between cortical activation and unimanual tasks,no significant correlations were observed with bimanual tasks.This study provides insights into the neural basis of bimanual coordination and fine motor skills in high-functioning patients after stroke,highlighting task-dependent neural responses.The findings also suggest that patients who exhibit better bimanual performance demonstrate more efficient cortical activation.Therefore,incorporating bilateral arm training in post-stroke rehabilitation is important for better outcomes.The combination of functional near-infrared spectroscopy with functional motor paradigms is valuable for assessing skills and developing targeted interventions in stroke rehabilitation.

Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

Possible Cortical Spreading Depression Recorded Intraoperatively Following a Generalized Seizure: Illustrative Case

Background: We present a compelling case fitting the phenomenon of cortical spreading depression detected by intraoperative neurophysiological monitoring (IONM) following an intraoperative seizure during a craniotomy for revascularization. Cortical spreading depression (CSD, also called cortical spreading depolarization) is a pathophysiological phenomenon whereby a wave of depolarization is thought to propagate across the cerebral cortex, creating a brief period of relative neuronal inactivity. The relationship between CSD and seizures is unclear, although some literature has made a correlation between seizures and a cortical environment conducive to CSD. Methods: Intraoperative somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) were monitored continuously during the craniotomy procedure utilizing standard montages. Electrophysiological data from pre-ictal, ictal, and post-ictal periods were recorded. Results: During the procedure, intraoperative EEG captured a generalized seizure followed by a stepwise decrease in somatosensory evoked potential cortical amplitudes, compelling for the phenomenon of CSD. The subsequent partial recovery of neuronal function was also captured electrophysiologically. Discussion: While CSD is considered controversial in some aspects, intraoperative neurophysiological monitoring allowed for the unique analysis of a case demonstrating a CSD-like phenomenon. To our knowledge, this is the first published example of this phenomenon in which intraoperative neurophysiological monitoring captured a seizure, along with a stepwise subsequent reduction in SSEP cortical amplitudes not explained by other variables.

Application of the cortical bone trajectory technique in posterior lumbar fixation

The cortical bone trajectory(CBT) is a novel technique in lumbar fixation and fusion.The unique caudocephalad and medial-lateral screw trajectories endow it with excellent screw purchase for vertebral fixation via a minimally invasive method.The combined use of CBT screws with transforaminal or posterior lumbar interbody fusion can treat a variety of lumbar diseases,including spondylolisthesis or stenosis,and can also be used as a remedy for revision surgery when the pedicle screw fails.CBT has obvious advantages in terms of surgical trauma,postoperative recovery,prevention and treatment of adjacent vertebral disease,and the surgical treatment of obese and osteoporosis patients.However,the concept of CBT internal fixation technology appeared relatively recently;consequently,there are few relevant clinical studies,and the long-term clinical efficacy and related complications have not been reported.Therefore,large sample and prospective studies are needed to further reveal the long-term complications and fusion rate.As a supplement to the traditional pedicle trajectory fixation technique,the CBT technique is a good choice for the treatment of lumbar diseases with accurate screw placement and strict indications and is thus deserving of clinical recommendation.

Alpha2-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury

Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.

Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury:a resting-state functional MRI study

Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

Antioxidant procyanidin B2 protects oocytes against cryoinjuries via mitochondria regulated cortical tension

Background:Irreversible cryodamage caused by oocyte vitrification limited its wild application in female fertility preservation.Antioxidants were always used to antagonist the oxidative stress caused by vitrification.However,the comprehensive mechanism underlying the protective role of antioxidants has not been studied.Procyanidin B2(PCB2)is a potent natural antioxidant and its functions in response to vitrification are still unknown.In this study,the effects of PCB2 on vitrified-thawed oocytes and subsequent embryo development were explored,and the mechanisms underlying the protective role of PCB2 were systematically elucidated.Results:Vitrification induced a marked decline in oocyte quality,while PCB2 could improve oocyte viability and further development after parthenogenetic activation.A subsequent study indicated that PCB2 effectively attenuated vitrification-induced oxidative stress,rescued mitochondrial dysfunction,and improved cell viability.Moreover,PCB2 also acts as a cortical tension regulator apart from strong antioxidant properties.Increased cortical tension caused by PCB2 would maintain normal spindle morphology and promote migration,ensure correct meiosis progression and finally reduce the aneuploidy rate in vitrified oocytes.Further study reveals that ATP biosynthesis plays a crucial role in cortical tension regulation,and PCB2 effectively increased the cortical tension through the electron transfer chain pathway.Additionally,PCB2 would elevate the cortical tension in embryo cells at morula and blastocyst stages and further improve blastocyst quality.What's more,targeted metabolomics shows that PCB2 has a beneficial effect on blastocyst formation by mediating saccharides and amino acids metabolism.Conclusions:Antioxidant PCB2 exhibits multi-protective roles in response to vitrification stimuli through mitochondria-mediated cortical tension regulation.

Experimental Investigation of Material Removal in Elliptical Vibration Cutting of Cortical Bone

To benefit tissue removal and postoperative rehabilitation,increased efficiency and accuracy and reduced operating force are strongly required in the osteotomy.A novel elliptical vibration cutting(EVC)has been introduced for bone cutting compared with conventional cutting(CC)in this paper.With the assistance of high-speed microscope imaging and the dynamometer,the material removals of cortical bone and their cutting forces from two cutting regimes were recorded and analysed comprehensively,which clearly demonstrated the chip morphology improvement and the average cutting force reduction in the EVC process.It also revealed that the elliptical vibration of the cutting tool could promote fracture propagation along the shear direction.These new findings will be of important theoretical and practical values to apply the innovative EVC process to the surgical procedures of the osteotomy.

Cross-sectional associations between cortical thiclmess and physical activity in older adults with spontaneous memory complaints:The MAPT Study

Background:Age-related changes in brain structure may constitute the starting point for cerebral function alteration.Physical activity(PA)demonstrated favorable associations with total brain volume,but its relationship with cortical thickness(CT)remains unclear.We investigated the cross-sectional associations between PA level and CT in community-dwelling people aged 70 years and older.Methods:A total of 403 older adults aged 74.8±4.0 years(mean±SD)who underwent a baseline magnetic resonance imaging examination and who had data on PA and confounders were included.PA was assessed with a questionnaire.Participants were categorized according to PA levels.Multiple linear regressions were used to compare the brain CT(mm)of the inactive group(no PA at all)with 6 active groups(growing PA levels)in 34 regions of interest.Results:Compared with inactive persons,people who achieved PA at a level of 1500-1999 metabolic equivalent task-min/week(i.e.,about6-7 h of brisk walking for exercise) and those who achieved it at 2000-2999 metabolic equivalent task-min/week(i.e.,8-11 h of brisk walking for exercise)had higher CT in the fusiform gyrus and the temporal pole.Additionally,dose-response associations between PA and CT were found in the fusiform gyrus(B=0.011,SE=0.004,adj.p=0.035),the temporal pole(B=0.026,SE=0.009,adj.p=0.048),and the caudal middle frontal gyrus,the entorhinal,medial orbitofrontal,lateral occipital,and insular cortices.Conclusion:This study demonstrates a positive association between PA level and CT in temporal areas such as the fusiform gyrus,a brain region often associated to Alzheimer’s disease in people aged 70 years and older.Future investigations focusing on PA type may help to fulfil remaining knowledge gaps in this field.

Effects of Rhynchophylline on L type Calcium Channels in Isolated Rat Cortical Neurons During Acute Hypoxia

Aim: To study the effects of rhynchophylline (Rhy) on the L type calcium channels in freshly dissociated cortical neurons of Wistar rats during acute hypoxia. Methods: Cell attached configuration of patch clamp technique. L type calcium channel was activated by stepping from 40 mV to 0 mV. Results: The results showed that the L type calcium channels of cortical neurons were activated by acute hypoxia. The mean open time of the channel was increased, the mean close time decreased and the open state probability raised during acute hypoxia. Rhy (15 and 30μmol·L -1 ) in concentration dependent manner blocked activity of the channels. The drug shortened the mean open time of the channels from 8 87 ms to 3 03 ms and 2 23 ms ( P 【0 001), prolonged the mean close time from 9 23 ms to 38 84 ms and 54 43 ms ( P 【0 001), and decreased the open state probability from 0 142 to 0 031 and 0 025 ( P 【0 001) under the hypoxia condition, respectively. The effects of Rhy were similar to but weaker than those of verapamil (15 μmol·L -1 ). Conclusion: The study confirmed that Rhy has the blockade effects on L type calcium channels in cortical neurons of rats during hypoxia, by which it protects the brain from hypoxic injury.

Acute lesions of primary visual cortical areas in adult cats inactivate responses of neurons in higher visual cortices

Psychophysical studies suggest that lateral extrastriate visual cortical areas in cats may mediate the sparing of vision largely by network reorganization following lesions of early visual cortical areas. To date, however, there is little direct physiological evidence to support this hypothesis. Using in vivo single-anit recording techniques, we examined the response of neurons in areas 19, 21, and 20 to different types of visual stimulation in cats with or without acute bilateral lesions in areas 17 and 18. Our results showed that, relative to the controls, acute lesions inactivated the response of 99.3% of neurons to moving gratings and 93% of neurons to flickering square stimuli＇in areas 19, 21, and 20. These results indicated that acute lesions of primary visual areas in adult eats may impair most visual abilities. Sparing of vision in cats with neonatal lesions in early visual cortical areas may result largely from a postoperative reorganization of visual pathways from subcortical nucleus to extrastriate visual cortical areas.

Cortical plasticity and nerve regeneration after peripheral nerve injury

With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.

Oxidative Stress and Apoptotic Changes of Rat Cerebral Cortical Neurons Exposed to Cadmium in Vitro

Objective To investigate the cytotoxic mechanism of cadmium（Cd） on cerebral cortical neurons.Methods The primary cultures of rat cerebral cortical neurons were treated with different concentrations of cadmium acetate（0,5,10,and 20 μmol/L）,and then the cell viability,apoptosis,ultrastructure,intracellular [Ca2＋]i and reactive oxygen species（ROS） levels,mitochondrial membrane potential（ΔΨ）,activities of catalase（CAT） and superoxide dismutase（SOD） were measured.Results A progressive loss in cell viability and an increased number of apoptotic cells were observed.In addition,Cd-induced apoptotic morphological changes in cerebral cortical neurons were also demonstrated by Hoechst 33258 staining.Meanwhile,ultrastructural changes were distortion of mitochondrial cristae and an unusual arrangement.Simultaneously,elevation of intracellular [Ca2＋]i and ROS levels,depletion of ΔΨ were revealed in a dose-dependent manner during the exposure.Moreover,CAT and SOD activities in the living cells increased significantly.Conclusion Exposure of cortical neurons to different doses of Cd led to cellular death,mediated by an apoptotic mechanism,and the apoptotic death induced by oxidative stress may be a potential reason.And the disorder of intracellular homeostasis caused by oxidative stress and mitochondrial dysfunction may be a trigger for apoptosis in cortical neurons.

Adrenal myelolipoma within myxoid cortical adenoma associated with Conn's syndrome

The coexistence of myelolipoma within adrenal cortical adenoma is extremely rare,for both tumors present usually as separate entities.There are only 16 such cases reported worldwide.To the best of our knowledge,the case we reported here is the first one of myxoid adrenal cortical adenoma associated with myelolipoma reported.A 32-year-old Chinese woman with 4-year history of hypertension was presented in our study.Computed tomography(CT)of the abdomen showed a large heterogene- ously-enhancing mass(4.5 cm in diameter)in the left suprarenal region.Clinical history and laboratory results suggest a metabolic disorder as Conn's syndrome.The patient underwent a left adrenalectomy,and a histopathological study confirmed the mass to be a myxoid adrenal cortical adenoma containing myelolipoma.The patient was postoperatively well and discharged uneventfully.In the present case report,we also discuss the etiology of simultaneous myelolipoma and adrenal adenoma associated with Conn's syndrome,and the methods of the diagnosis and differential diagnosis.

Involvement of PI3K/Akt Pathway in the Neuroprotective Effect of Sonic Hedgehog on Cortical Neurons under Oxidative Stress

The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical neurons against oxidative stress. The present study was aimed to further examine the underlying mechanism. The cortical neurons were obtained from one-day old Sprague-Dawley neonate rats. Hydrogen peroxide (H2O2, 100 μmol/L) was used to treat neurons for 24h to induce oxidative stress. Exogenous SHH (3μg/mL) was employed to activate the SHH pathway, and cyclopamine (20 μmol/L), a specific SHH signal inhibitor, to block SHH pathway. LY294002 (20 μmol/L) were used to pretreat the neurons 30 min before H2O2 treatment and selectively inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The cell viability was measured by MTT and apoptosis rate by flow cytometry analysis. The expression of p38, p-p38, ERK, p-ERK, Akt, p-Akt, Bcl-2, and Bax in neurons was detected by immunoblotting. The results showed that as compared with H2O2 treatment, exogenous SHH could increase the expression of p-Akt by 20% and decrease the expression of p-ERK by 33%. SHH exerted no significant effect on p38 mitogen-activated protein kinase (p38 MAPK) pathway. Blockade of PI3K/Akt pathway by LY294002 decreased the cell viability by 17% and increased the cell apoptosis rate by 2-fold. LY294002 treatment could up-regulate the expression of the proapoptotic gene Bax by 12% and down-regulate the expression of the antiapoptotic gene Bcl-2 by 54%. In conclusion, SHH pathway may activate PI3K/Akt pathway and inhibit the activation of the ERK pathway in neurons under oxidative stress. The PI3K/Akt pathway plays a key role in the neuroprotection of SHH. SHH/PI3K/Bcl-2 pathway may be implicated in the protection of neurons against H2O2-induced apoptosis.

Silencing Huwe1 reduces apoptosis of cortical neurons exposed to oxygen-glucose deprivation and reperfusion

HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, including p53, Mcl-1, Cdc6 and N-myc, thereby playing a critical role in apoptosis and neurogenesis. However, the role of Huwe1 in brain ischemia and reperfusion injury remains unclear. Therefore, in this study, we investigated the role of Huwe1 in an in vitro model of ischemia and reperfusion injury. At 3 days in vitro, primary cortical neurons were transduced with a control or shRNA-Huwe1 lentiviral vector to silence expression of Huwe1. At 7 days in vitro, the cells were exposed to oxygen-glucose deprivation for 3 hours and reperfusion for 24 hours. To examine the role of the c-Jun N-terminal kinase(JNK)/p38 pathway, cortical neurons were pretreated with a JNK inhibitor(SP600125) or a p38 MAPK inhibitor(SB203508) for 30 minutes at 7 days in vitro, followed by ischemia and reperfusion. Neuronal apoptosis was assessed by TUNEL assay. Protein expression levels of JNK and p38 MAPK and of apoptosis-related proteins(p53, Gadd45 a, cleaved caspase-3, Bax and Bcl-2) were measured by western blot assay. Immunofluorescence labeling for cleaved caspase-3 was performed. We observed a significant increase in neuronal apoptosis and Huwe1 expression after ischemia and reperfusion. Treatment with the shRNA-Huwe1 lentiviral vector markedly decreased Huwe1 levels, and significantly decreased the number of TUNEL-positive cells after ischemia and reperfusion. The silencing vector also downregulated the pro-apoptotic proteins Bax and cleaved caspase-3, and upregulated the anti-apoptotic proteins Gadd45 a and Bcl-2. Silencing Huwe1 also significantly reduced p-JNK levels and increased p-p38 levels. Our findings show that downregulating Huwe1 affects the JNK and p38 MAPK signaling pathways as well as the expression of apoptosis-related genes to provide neuroprotection during ischemia and reperfusion. All animal experiments and procedures were approved by the Animal Ethics Committee of Sichuan University, China in January 2018(approval No. 2018013).

Patterns of cortical reorganization in facial synkinesis:a task functional magnetic resonance imaging study

Facial synkinesis,a sequela of peripheral facial nerve palsy,is characterized by simultaneous involuntary facial movement during a voluntary desired one.Maladaptive cortical plasticity might be involved in the dysfunction of facial muscles.This cohort study investigated the cortical functional alterations in patients with unilateral facial synkinesis,using the task functional magnetic resonance imaging.Facial motor tasks,including blinking and smiling,were performed by 16 patients（aged 30.6 ± 4.5 years,14 females/2 males） and 24 age-and sex-matched healthy controls（aged 29.1 ± 4.2 years,19 females/5 males）.Results demonstrated that activation in the cortico-facial motor representation area was lower during tasks in patients with facial synkinesis compared with healthy controls.Facial movements on either side performed by patients caused more intensive activation of the supplementary motor area on the contralateral side of the affected face,than those on the unaffected side.Our results revealed that there was cortical reorganization in the primary sensorimotor area and the supplementary motor area.This study was registered in Chinese Clinical Trial Registry（registration number： Chi CTR1800014630）.