Secretory Clusterin Inhibits Dopamine Neuron Apoptosis in MPTP Mice by Preserving Autophagy Activity.

Secretory clusterin (sCLU) plays an important role in the research progress of nervous system diseases. However, the physiological function of sCLU in Parkinson's disease (PD) are unclear. The purpose of this study was to examine the effects of sCLU-mediated autophagy on cell survival and apoptosis inhibition in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. We found that MPTP administration induced prolonged pole-climbing time, shortened traction time and rotarod time, significantly decreased TH protein expression in the SN tissue of mice. In contrast, sCLU -treated mice took less time to climb the pole and had an extended traction time and rotating rod time. Meanwhile, sCLU intervention induced increased expression of the TH protein in the SN of mice. These results indicated that sCLU intervention could reduce the loss of dopamine neurons in the SN area and alleviate dyskinesia in mice. Furthermore, MPTP led to suppressed viability, enhanced apoptosis, an increased Bax/Bcl-2 ratio, and cleaved caspase-3 in the SN of mice, and these effects were abrogated by sCLU intervention. In addition, MPTP increased the levels of P62 protein, decreased Beclin1 protein, decreased the ratio of LC3B-II/LC3B-I, and decreased the numbers of autophagosomes and autophagolysosomes in the SN tissues of mice. These effects were also abrogated by sCLU intervention. Activation of PI3K/AKT/mTOR signaling with MPTP inhibited autophagy in the SN of MPTP mice; however, sCLU treatment activated autophagy in MPTP-induced PD mice by inhibiting PI3K/AKT/mTOR signaling. These data indicated that sCLU treatment had a neuroprotective effect in an MPTP-induced model of PD.

Utility of labial salivary gland biopsy in the histological diagnosis of neuronal intranuclear inclusion disease.

BACKGROUND AND PURPOSE: Neuronal intranuclear inclusion disease (NIID) poses a diagnostic challenge because of its diverse clinical manifestations. Detection of intranuclear inclusions remains the primary diagnostic criterion for NIID. Skin biopsies have traditionally been used, but concerns exist regarding postoperative complications and scarring. We sought to investigate the diagnostic utility of labial salivary gland biopsy, a less invasive alternative. METHODS: This study included a total of 19 patients and 11 asymptomatic carriers who underwent labial gland biopsies, while 10 patients opted for skin biopsies. All these individuals were confirmed to have pathogenic GGC repeat expansions in the NOTCH2NLC gene. The control group comprised 20 individuals matched for age and sex, all with nonpathogenic GGC repeat expansions, and their labial gland tissue was sourced from oral surgery specimens. RESULTS: Labial gland biopsies proved to be a highly effective diagnostic method in detecting eosinophilic intranuclear inclusions in NIID patients. The inclusions showed positive staining for p62 and ubiquitin, confirming their pathological significance. The presence of uN2CpolyG protein in the labial gland tissue further supported the diagnosis. Importantly, all patients who underwent lip gland biopsy experienced fast wound healing without any noticeable scarring. In contrast, skin biopsies led to varying degrees of scarring and one instance of a localized infection. CONCLUSION: Labial salivary gland biopsy emerged as a minimally invasive, efficient diagnostic method for NIID, with rapid healing and excellent sensitivity.

Remote limb ischemic postconditioning inhibits microglia pyroptosis by modulating HGF after acute ischemia stroke.

The repetitive inflation-deflation of a blood pressure cuff on a limb is known as remote limb ischemic postconditioning (RIPostC). It prevents brain damage induced by acute ischemia stroke (AIS). Pyroptosis, executed by the pore-forming protein gasdermin D (GSDMD), is a type of regulated cell death triggered by proinflammatory signals. It contributes to the pathogenesis of ischemic brain injury. However, the effects of RIPostC on pyroptosis following AIS remain largely unknown. In our study, linear correlation analysis confirmed that serum GSDMD levels in AIS patients upon admission were positively correlated with NIHSS scores. RIPostC treatment significantly reduced GSDMD level compared with patients without RIPostC at 3 days post-treatment. Besides, middle cerebral artery occlusion (MCAO) surgery was performed on C57BL/6 male mice and RIPostC was induced immediately after MCAO. We found that RIPostC suppressed the activation of NLRP3 inflammasome to reduce the maturation of GSDMD, leading to decreased pyroptosis in microglia after AIS. Hepatocyte growth factor (HGF) was identified using the high throughput screening. Importantly, HGF siRNA, exogenous HGF, and ISG15 siRNA were used to reveal that HGF/ISG15 is a possible mechanism of RIPostC regulation in vivo and in vitro.

Comparative Analysis of Acute Levodopa Challenge Test and the Outcomes of Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: We study the correlation between the preoperative levodopa challenge test and the efficacy of deep brain stimulation (DBS) surgery in Parkinson's disease (PD). METHODS: Fifty patients with PD who underwent DBS treatment in our hospital from October 2016 to October 2017 were enrolled in this study. Using the Unified Parkinson Disease Rating Scale-III (UPDRS-III) as an indicator, we analyzed the improvement in motor symptoms on the levodopa challenge test and by DBS surgery. We also discussed the correlation between the effects of the levodopa challenge test and DBS surgery. RESULTS: There was no correlation between the results of the levodopa challenge test and DBS surgery. There was a linear correlation between muscle rigidity and bradykinesia, whereas the linear correlation between other symptoms was weak. CONCLUSION: The levodopa challenge test can be used as a screening tool for patients undergoing DBS surgery, and can predict the degree of improvement in muscle rigidity and bradykinesia surgery. However, the prediction of the degree of improvement of total motor symptoms is poor.

NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice.

BACKGROUND: Secondary brain damage caused by the innate immune response and subsequent proinflammatory factor production is a major factor contributing to the high mortality of intracerebral haemorrhage (ICH). Nucleotide-binding oligomerization domain 1 (NOD1)/receptor-interacting protein 2 (RIP2) signalling has been reported to participate in the innate immune response and inflammatory response. Therefore, we investigated the role of NOD1/RIP2 signalling in mice with collagenase-induced ICH and in cultured primary microglia challenged with hemin. METHODS: Adult male C57BL/6 mice were subjected to collagenase for induction of ICH model in vivo. Cultured primary microglia and BV2 microglial cells (microglial cell line) challenged with hemin aimed to simulate the ICH model in vitro. We first defined the expression of NOD1 and RIP2 in vivo and in vitro using an ICH model by western blotting. The effect of NOD1/RIP2 signalling on ICH-induced brain injury volume, neurological deficits, brain oedema, and microglial activation were assessed following intraventricular injection of either ML130 (a NOD1 inhibitor) or GSK583 (a RIP2 inhibitor). In addition, levels of JNK/P38 MAPK, IκBα, and inflammatory factors, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, and inducible nitric oxide synthase (iNOS) expression, were analysed in ICH-challenged brain and hemin-exposed cultured primary microglia by western blotting. Finally, we investigated whether the inflammatory factors could undergo crosstalk with NOD1 and RIP2. RESULTS: The levels of NOD1 and its adaptor RIP2 were significantly elevated in the brains of mice in response to ICH and in cultured primary microglia, BV2 cells challenged with hemin. Administration of either a NOD1 or RIP2 inhibitor in mice with ICH prevented microglial activation and neuroinflammation, followed by alleviation of ICH-induced brain damage. Interestingly, the inflammatory factors interleukin (IL)-1ß and tumour necrosis factor-α (TNF-α), which were enhanced by NOD1/RIP2 signalling, were found to contribute to the NOD1 and RIP2 upregulation in our study. CONCLUSION: NOD1/RIP2 signalling played an important role in the regulation of the inflammatory response during ICH. In addition, a vicious feedback cycle was observed between NOD1/RIP2 and IL-1ß/TNF-α, which could to some extent result in sustained brain damage during ICH. Hence, our study highlights NOD1/RIP2 signalling as a potential therapeutic target to protect the brain against secondary brain damage during ICH.

Re-defining the clinicopathological spectrum of neuronal intranuclear inclusion disease.

BACKGROUND: The rapidly increasing case reports revealed that neuronal intranuclear inclusion disease (NIID) had concomitant other system symptoms besides nervous system symptoms. In this study, we systematically evaluated the symptoms, signs, auxiliary examination, and pathological changes in different systems in NIID patients. METHODS: NIID patients were confirmed by examining GGC repeats in the NOTCH2NLC gene. Clinical data of NIID patients including symptoms, signs, and auxiliary examinations were collected for analysis. Ubiquitin and p62 were detected in different tissues from previous surgical samples. RESULTS: Fifty-one NIID patients from 17 families were included in this study. Except neurological symptoms, clinical manifestations from other systems were very notable and diverse. The proportions of different system symptoms were 88.2% in nervous system, 78.4% in respiratory system, 72.5% in circulatory system, 72.5% in locomotor system, 66.7% in urinary system, 64.7% in digestive system, 61.5% in reproductive system, and 50.0% in endocrine system. In addition, other common symptoms included sexual dysfunction (43.1%), pupil constriction (56.9%), blurred vision (51.0%), and hearing loss (23.5%). Ubiquitin and p62-positive cells were found in different tissues and systems in 24 NIID patients with previous surgery. Initial symptoms of NIID and median onset age in different systems also revealed system heterogeneity of NIID. INTERPRETATION: For the first time, we systematically demonstrated that NIID is a heterogeneous and systemic neurodegenerative disease by providing clinical and pathological evidence. In addition to the nervous system, the clinical symptomatic and pathological spectrum of NIID has been extended to almost all systems.

Trousseau Syndrome Related Cerebral Infarction: Clinical Manifestations, Laboratory Findings and Radiological Features.

PURPOSE: We summarized the clinical manifestations, laboratory data, and brain MRI of patients with Trousseau syndrome related cerebral infarction and compared them to patients with other types of cerebral infarction. Through our present research, we hope to aid the neurologists in recognizing and diagnosing this syndrome. METHODS: A total of 31 patients at our institution were identified with cerebral infarction resulting from Trousseau syndrome. We have also selected the 180 patients who have suffered from cerebral infarction as control groups and these patients were distributed to large-artery atherosclerosis group; cardio-embolism group; small-artery occlusion group, according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The clinical data and neuroimage of these patients were collected. RESULTS: All our 31 cancer patients were confirmed by pathological biopsy to be adenocarcinomas and the most common cancers are gastric and lung cancers. Patients with Trousseau syndrome exhibited high serum carbohydrate antigen CEA, CA 125 and CA 199 levels. Compared to patients with other types of cerebral infarction, patients with Trousseau syndrome had an increased severity and worse prognosis. Besides, patients had the highest mean level of plasma D-dimer. We also found multiple lesions in multiple vascular territories was the most frequent type of DWI patterns in patients of Trousseau syndrome. CONCLUSIONS: Trousseau syndrome can progress rapidly and become life-threatening. For patients who developed unexplained cerebral infarction involving multiple arterial territories, with elevated plasma D-dimer and cancer antigens, Trousseau syndrome should always be considered.

Melatonin Attenuates Thrombin-induced Inflammation in BV2 Cells and Then Protects HT22 Cells from Apoptosis.

Increasing evidence has revealed that the uncontrolled thrombin-induced inflammation following intracerebral hemorrhage (ICH) plays a key role in ICH. Oxidative stress and neuroinflammatory responses are interdependent and bidirectional events. Melatonin is now recognized as an antioxidant and a free radical scavenger due to its roles in various physiological and pathological processes. The aim of this study was to explore the molecular mechanisms underlying the effects of melatonin on thrombin-induced microglial inflammation and its indirect protection of HT22 cells from p53-associated apoptosis. Melatonin treatment attenuated the expression of IL-1ß, IL-18, cleaved caspase-1, and NLRP3 and decreased the production of reactive oxygen species (ROS), revealing its inhibitory effects against ROS-NLRP3 inflammasome activation. In further experiments investigating the protection conferred by melatonin, incubating HT22 cells with conditioned medium (CM) from thrombin-stimulated microglia induced HT22 cell apoptosis, and this effect was reversed after treating CM with either melatonin or N-acetyl-L-cysteine (NAC). Additionally, the Bax/Bcl-2 ratio and the levels of cleaved caspase-3 and p53 were markedly lower in the cells cultured in thrombin + melatonin-CM than in the cells cultured in thrombin-CM. Furthermore, the levels of MMP, ROS, SOD, MDA, and GSH-PX in bystander HT22 cells suggested that melatonin decreased HT22 cell apoptosis instigated via the p53-associated apoptotic pathway. Therefore, these findings strongly indicate the anti-inflammatory properties of melatonin that may suppress ROS-NLRP3 inflammasome activation and protect HT22 cells against apoptosis by inhibiting the ROS-mediated p53-dependent mitochondrial apoptotic pathway.

Surgery and Guillain-Barré Syndrome: A Single-Center Retrospective Study Focused on Clinical and Electrophysiological Subtypes.

BACKGROUND: Surgery-related Guillain-Barré syndrome (GBS) is often underestimated and sometimes difficult to diagnose. This study aimed to elucidate the clinical features and electrophysiological subtypes of post-surgical GBS. METHODS: We retrospectively reviewed 17 patients who developed post-surgical GBS after a recent surgery between 2015 and 2019. Clinical characteristics, electrophysiological examinations, lumbar puncture results and prognosis were assessed. As controls, we selected 66 patients hospitalized with non-surgical GBS. RESULTS: The median duration from the surgery to the onset of GBS symptoms was 16.0 days. The main types of surgeries preceding GBS were orthopedic, gastrointestinal and neurosurgery. Symmetrical distal limbs weakness was present in all 17 post-surgical GBS patients. The incidence of respiratory failure, autonomic dysfunction and muscle atrophy in post-surgical GBS patients was significantly higher than that in non-surgical GBS patients. Hughes Functional Grading Scale (HFGS) scores were also higher in the post-surgical GBS group both at the time of peak disease and 6 months after discharge. Electrophysiological studies revealed significant motor amplitudes reduction with relative preserved nerve conduction velocities and distal latencies, suggesting axonal subtypes of GBS. CONCLUSION: GBS should be considered in patients with rapidly progressive muscle weakness after surgery. Such patients often exhibit axonal subtypes of GBS with severe motor dysfunction, high risk of respiratory failure, and poor prognosis.

An analysis of the clinical and imaging features of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

Objective: To investigate the clinical features and imaging characteristics of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).Methods: Seventeen patients with MELAS diagnosed in the Affiliated Hospital of Xuzhou Medical University from July 2014 to August 2018 were enrolled in this study and their clinical manifestations, imaging and histopathological features were retrospectively analysed. We also discussed and summarised the related literature.Results: All of the 12 patients had seizures; stroke-like episodes in 12 cases; audio-visual impairment in 12 cases; headache in six cases; dysplasia in four cases; mental retardation in three cases; ataxia in two cases. On cranial magnetic resonance (MR) scans, the most common manifestations were in temporal-occipital-parietal lobe, cortical or subcortical areas as well as frontal lobe, thalamus, and basal ganglia showing long or equal T1 signals, long T2 signals, and hyperintense or iso-intense diffusion-weighted imaging (DWI) signals accompanied by ventricular enlargement and brain atrophy. MR spectroscopy showed that lactic acid peaks could be found in lesion sites, normal brain tissues, and cerebrospinal fluid. Muscle biopsy and genetic testing are the gold standard for diagnosing MELAS, muscle biopsy revealed COX-negative muscle fibres and SDH-stained red ragged fibres (RRF) under the sarcolemma. Mutations of mtDNA A3243G locus were common on gene testing. Improvement of mitochondrial function was observed after symptomatic and supportive treatment.Conclusion: MELAS should be considered for patients with epileptic seizures, headache, stroke-like episodes, extraocular palsy, cognitive decline and other clinical manifestations with the lesion located in the temporal-occipital-parietal lobe regardless of the distribution of blood vessels, and further examinations including muscle biopsy and gene testing should be performed to confirm the diagnosis.

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice.

BACKGROUND: Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model. METHODS: Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl's and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention. RESULTS: Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction. CONCLUSION: Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

Recent progress in neuronal intranuclear inclusion disease: a review of the literature.

OBJECTIVE: To summarize the current understanding of neuronal intranuclear inclusion disease (NIID) and improve the understanding of the physician about this condition. METHODS: We searched PubMed with keywords related to NIID and selected publications which seemed appropriate. We analyzed its clinical features, pathogenesis, evaluation methods, treatment options, and research prospectives. RESULTS: NIID is a degenerative condition which can affect multiple organ systems especially central nervous system. Its clinical features greatly vary, and making the exact diagnosis is often difficult. There are several genes which have been associated with this disorder. Some specific signs on diffusion-weighted-imaging (DWI) sequence of magnetic resonance (MR) imaging are characteristics to NIID. CONCLUSION: Intranuclear inclusions have been found in various nonneural cells of the body; therefore, the term systemic intranuclear inclusion disease is, perhaps, better suited to explain this disorder. There are several disorders which need to be ruled out before making the diagnosis, and neuroimaging and biopsy analysis should be combined to support the diagnosis.

A Rare Case of Bilateral Vertebral Artery Dissection Associated with Essential Thrombocythemia.

A young patient presented to our hospital with ischemic stroke. She underwent a routine blood test, head computed tomography (CT), brain magnetic resonance imaging, a bone marrow biopsy, and CT angiography. Her diagnosis was a bilateral vertebral artery dissection associated with essential thrombocythemia (ET). She was treated with antiplatelet therapy and a stent implantation. The association of bilateral vertebral artery dissection with ET is rare. An early diagnosis and timely management is key to the best outcome.

An Analysis of Clinical Characteristics of Rare Bilateral Cerebral Peduncular Infarction.

Objective: To investigate the anatomical characteristics, clinical manifestations, and imaging features of bilateral cerebral peduncular infarction. Methods: A retrospective analysis was performed on 11 patients diagnosed with bilateral cerebral peduncular infarction in the Affiliated Hospital of Xuzhou Medical University from December 2014 to December 2018. Their clinical and imaging features were analyzed and summarized in combination with the relevant national and international literature. Results: Among all the patients, there were eight cases with a history of hypertension, four cases with a history of diabetes mellitus, and four cases with a history of smoking. Conscious disturbance was observed in nine cases, quadriplegia in seven cases, pseudobulbar paralysis in three cases, and ataxia in one case. Brain magnetic resonance (MR) scans of bilateral cerebral peduncles showed patchy abnormal shadows with a hypointense signal on T1-weighted imaging (T1WI) and apparent diffusion coefficient (ADC) and hyperintense signal on T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). Computed tomography angiography (CTA) scans of head and neck showed severe stenosis or occlusion of vertebral artery, basilar artery, or posterior cerebral artery. All the patients received standardized treatment for cerebral infarction. Six patients died while five were left disabled. Conclusion: Bilateral cerebral peduncle infarction may be related to cerebral perfusion insufficiency caused by the stenosis or occlusion of vertebrobasilar artery and its branches. The main clinical manifestations are locked-in syndrome and persistent vegetative state. The specific imaging feature of "Mickey Mouse ear"-like infarction is associated with a poor prognosis.

The aetiologies of unilateral oculomotor nerve palsy: a clinical analysis on 121 patients.

Background and purpose: To strengthen the understanding, increase the early diagnostic rate, and improve the outcome of unilateral oculomotor nerve palsy through the analysis of the 121 patients suffering from this disease in our hospital. Methods: A retrospective study was performed on the 121 patients with unilateral oculomotor nerve palsy diagnosed at the Affiliated Hospital of Xuzhou Medical University from October 2014 to October 2015. The clinical data, such as gender, age, aetiology, clinical features, laboratory tests, and six months follow up reports were analyzed. Results: The main causes identified in the 121 patients with unilateral oculomotor nerve palsy were intracranial aneurysm (29.8%), diabetic peripheral neuropathy (26.5%), painful ophthalmoplegia (9.9%), and other causes (33.9%). The results from the six month follow up showed that in all the patients, 53.7% were fully recovered, 38.0% improved, and 8.3% had no significant change in symptoms. The results also indicated that the patients with diabetic peripheral neuropathy had the best outcome with 71.9% full recovery rate, which was significantly higher than that in the patients with intracranial aneurysm (36.1%, p < .05), and idiopathic causes (44.5%, p < .05). Conclusions: Our data indicates that intracranial aneurysm is the leading cause of unilateral oculomotor nerve palsy, and that diabetic peripheral neuropathy has better outcome. Understanding the common causes and clinical features of unilateral oculomotor nerve paralysis is helpful for its early diagnosis and treatment.

ADENOSINE A1 RECEPTOR AGONIST PROTECTS AGAINST HIPPOCAMPAL NEURONAL INJURY AFTER LITHIUM CHLORIDE-PILOCARPINE-INDUCED EPILEPSY.

BACKGROUND: Adenosine A1 receptor (AA1R) is widely present in the central nervous system, exerting brain protective antiepileptic effects, mainly by binding corresponding G proteins. We evaluated the neuroprotective effects of AA1R on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy in rats. MATERIALS AND METHODS: A total of 60 male SD rats were randomly divided into four groups (n = 15/group): normal control, epilepsy, epilepsy + AA1R antagonist (DPCPX), and epilepsy + AA1R agonist (2-CAdo). An epilepsy model was established through kindling by lithium chloride-pilocarpine. The four groups were observed on days 1, 14, and 30. Pathological and morphological changes of hippocampal neurons were observed by HE staining; apoptosis was detected by TUNEL assay. Caspase-3 and GABA receptor expressions were detected by Western blot. RESULTS: In the hippocampal CA3 area of the epilepsy group, the cellular structure was not neatly arranged, and some neurons were swelling, thick, and incomplete. Compared with the epilepsy group at the same time point, cells in the epilepsy + DPCPX group had an increased distortion, disorganization, edema, cytoplasmic vacuoles, and degeneration. In the epilepsy + 2-CAdo group, cell arrangement was regular and orderly, and structural damages were lessened. Compared with the normal control group at the same time point, the epilepsy group underwent evident neuronal apoptosis, with a significantly higher apoptotic index (AI) (p < 0.05). Compared with the epilepsy group, the neuronal apoptosis of the epilepsy + DPCPX group was boosted, and the AI significantly increased (p < 0.05). The neuronal apoptosis of the epilepsy + 2-CAdo group was inhibited, and the AI significantly decreased (p < 0.05). Compared with the epilepsy group, the caspase-3 expression levels of the epilepsy + DPCPX group on days 14 and 30 were significantly upregulated (p < 0.05), but those of the epilepsy + 2-CAdo group were significantly downregulated (p < 0.05). CONCLUSIONS: AA1R abated cell edema and reduced apoptosis, exerting neuroprotective effects on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy.

Mitochondrial transplantation attenuates lipopolysaccharide- induced depression-like behaviors.

The dysfunction of mitochondria plays important roles in the development of depression. Interestingly, increasing numbers of evidence show the therapeutic benefits of mitochondria transfer. Therefore, we hypothesized that injection of exogenous mitochondria would contribute to ameliorate depressive-like symptoms. In this study, the antidepressant-like effect of intravenous isolated mitochondria was evaluated on a lipopolysaccharide (LPS)- induced model of depression. The depressive-like behaviors were assessed using forced swim test (FST), tail suspension test (TST) and sucrose preference test. Besides, the neurogenesis, expression of brain-derived neurotrophic factor (BDNF), glial activation, neuroinflammation, oxidative stress and ATP production were determined in the hippocampus. The results showed that treatment of isolated mitochondria decreased the immobility time of mice in the FST and TST, and attenuated the decrease in sucrose preference test. Moreover, isolated mitochondria significantly reduced the activation of astrocyte and microglia as well as neuroinflammation (i.e. 1 L-1ß, TNF-α and COX-2), increased BDNF expression and neurogenesis, restored the dysfunction of ATP production and oxidative stress in inflammation- induced depression. Taken together, the data suggested for the first time that injection of isolated mitochondria ameliorated LPS- induced depressive-like behaviors. The new discovery for the present study provides that mitochondrial transplantation might act as a new therapeutic strategy for MDD.

Adenosine a1 receptor agonist protects against hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy

Abstract Background Adenosine A1 receptor (AA1R) is widely present in the central nervous system, exerting brain protective antiepileptic effects, mainly by binding corresponding G proteins. We evaluated the neuroprotective effects of AA1R on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy in rats. Materials and Methods A total of 60 male SD rats were randomly divided into four groups (n = 15/group): normal control, epilepsy, epilepsy + AA1R antagonist (DPCPX), and epilepsy + AA1R agonist (2-CAdo). An epilepsy model was established through kindling by lithium chloride-pilocarpine. The four groups were observed on days 1, 14, and 30. Pathological and morphological changes of hippocampal neurons were observed by HE staining; apoptosis was detected by TUNEL assay. Caspase-3 and GABA receptor expressions were detected by Western blot. Results In the hippocampal CA3 area of the epilepsy group, the cellular structure was not neatly arranged, and some neurons were swelling, thick, and incomplete. Compared with the epilepsy group at the same time point, cells in the epilepsy + DPCPX group had an increased distortion, disorganization, edema, cytoplasmic vacuoles, and degeneration. In the epilepsy + 2-CAdo group, cell arrangement was regular and orderly, and structural damages were lessened. Compared with the normal control group at the same time point, the epilepsy group underwent evident neuronal apoptosis, with a significantly higher apoptotic index (AI) (p < 0.05). Compared with the epilepsy group, the neuronal apoptosis of the epilepsy + DPCPX group was boosted, and the AI significantly increased (p < 0.05). The neuronal apoptosis of the epilepsy + 2-CAdo group was inhibited, and the AI significantly decreased (p < 0.05). Compared with the epilepsy group, the caspase-3 expression levels of the epilepsy + DPCPX group on days 14 and 30 were significantly upregulated (p < 0.05), but those of the epilepsy + 2-CAdo group were significantly downregulated (p < 0.05). Conclusions AA1R abated cell edema and reduced apoptosis, exerting neuroprotective effects on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy.

A rare case of small cell carcinoma of lung with intraventricular metastasis.

Our case report involves a Chinese patient who was presented to our hospital with the chief complaint of dizziness and double vision for one week. He was diagnosed with small cell carcinoma of lung in the past. The patient undertook various test at our hospital. His MR scan revealed an intraventricular metastasis from small cell carcinoma of lung which is very rare. We have analyzed the clinical data of this patient and related literature. We report this case to increase the awareness of this rare metastasis of small cell carcinoma of lung.

The clinical and imaging features of hypertrophic pachymeningitis: a clinical analysis on 22 patients.

OBJECTIVE: To explore the clinical and imaging features of patients with hypertrophic cranial pachymeningitis (HCP). METHODS: A retrospective study was performed on 22 patients with HCP diagnosed at the Affiliated Hospital of Xuzhou Medical University from February 2014 to September 2017. RESULTS: A headache was present as an initial symptom in 18 patients. The headache was associated with the loss of vision (2 cases), facial pain (1 case), and unsteady walking (1 case). Other symptoms included cranial nerve dysfunction (15 cases), cerebellar ataxia (4 cases), and sinus thrombosis (3 cases). In the laboratory tests, 7 patients showed an increased number of white blood cells, higher levels of C-reaction protein (CRP), and erythrocyte sedimentation rate (ESR). An elevated level of immunoglobulin G4 (IgG4) and the presence of the anti-neutrophil cytoplasmic antibody (ANCA) were found in 3 and 2 patients respectively. There were 17 patients who had abnormalities in their cerebrospinal fluid (CSF) on lumbar puncture. On magnetic resonance imaging (MRI), a local or generalized thickening was observed in the cerebral falx, the tentorium of the cerebellum, the fronto-parietal lobe, the occipito-parietal lobe, and the dura of skull base. A dural biopsy obtained in one case showed a variety of inflammatory changes. An immunohistochemical analysis revealed the positivity of CD138, IgG, and IgG4 in some cells. All 22 patients had a good response to corticosteroids. CONCLUSION: HCP mainly leads to a headache and the paralysis of multiple cranial nerves. A biopsy and MRI are often required and serve as the basis for the diagnosis and effective therapy.