Human Glioma Nude Mouse Xenograft Model in situ

Backgrounds: Surgery and chemotherapy are difficult because of the specific location of the glioma. The establishment of a suitable in situ model of glioma is the premise of the treatment of glioma. 8 week-old female BALB/c nude mice were chose to establish the glioma model. Methods: For the orthotopic glioma mice model, 1 × 105cells/5 μL U87-MG-Luc or U87-MG cells which were trypsinized and resuspended in sterile PBS were slowly injected into the right corpus striatum (1.8 mm lateral, 0.6 mm anterior to the bregma and 3.0 mm in depth) by a stereotactic fixation device using a mouse adaptor. Results: The othotopic U87 glioma mice model identified by imaging on IVIS Spectrum and magnetic resonance imaging after 2 weeks from surgery. H&E-stained tumor sections in brain of the mice model were also observed. Conclusions: After identification, the glioma mouse xenograft in situ model obtained could be used in the evaluation system of therapeutic drugs or methods.

Signaling Overlap between the Golgi Stress Response and Cysteine Metabolism in Huntington’s Disease

Huntington’s disease (HD) is caused by expansion of polyglutamine repeats in the protein huntingtin, which affects the corpus striatum of the brain. The polyglutamine repeats in mutant huntingtin cause its aggregation and elicit toxicity by affecting several cellular processes, which include dysregulated organellar stress responses. The Golgi apparatus not only plays key roles in the transport, processing, and targeting of proteins, but also functions as a sensor of stress, signaling through the Golgi stress response. Unlike the endoplasmic reticulum (ER) stress response, the Golgi stress response is relatively unexplored. This review focuses on the molecular mechanisms underlying the Golgi stress response and its intersection with cysteine metabolism in HD.

Non-Ketotic Hyperglycemia-Induced Hemichorea-Hemiballism, A Case Presentation

Hemiballism is a rare hyperkinetic movement disorder characterized by repetitive, uncontrolled movements unilateral /or bilateral extremities, develops as a result of insult to the contralateral basal ganglia. The leading source for this disorder is ischemia, followed by non-ketotic hyperglycemia with poorly controlled diabetes. Non-ketotic hyperglycemic induced hemichorea-hemiballism is an uncommon but unique etiology of unilateral neuro-parenchymal findings restricted to corpus striatum (caudate nucleus and putamen). Nonketotic hyperglycemia-induced hemichorea-hemiballism diagnosed by Cross-sectional imaging modalities (Computed tomography and Magnetic resonance imaging), Clinical results (hemichorea-hemiballism), Laboratory tests (elevated blood glucose and hemoglobin A1c levels).

Lipidomics Reveals Glycerophospholipid Metabolism Dysregulation in the Corpus Striatum of Mice Treated with Cefepime

Cefepime exhibits a broad spectrum of antimicrobial activity and thus is widely used for severe bacterial infection. Adverse effects on the central nervous system (CNS) have been reported in the patients treated with cefepime. Current explanation for the neurobehavioral effect of cefepime mainly attributes to its ability to across blood-brain barrier and to competitively bind to GABAergic receptor; however, the underlying mechanism is largely unknown. In this study, mice were intraperitoneally administered 80 mg/kg cefepime for different time period, including 1 day, 3 days, 5 days, 7 days and 10 days, and then LC/MS-MS-based metabolomics was used to investigate the effect of cefepime on the brain lipidomic profiling and metabolic pathway. Repeated cefepime treatment time-dependently caused anxiety-like behavior accompanied with the reduced locomotor activity in the open field test. Cefepime profoundly altered the lipid profile in the corpus striatum, and glycerophospholipid contributed to a large proportion among those significantly modified lipids. Cefepime also significantly modified acyl chain length and unsaturation of fatty acids. In addition, cefepime obviously altered the morphology of neurite, mitochondria and synaptic vesicles of striatal neuron in vitro. Collectively, our results show that cefepime reprograms glycerophospholipid metabolism of corpus striatum, which may underly its neurobehavioral effect.

Changes in the brain

This chapter explains the change which can be seen in the structure of the brain of someone with Huntington’s disease (HD). There is a recognized pattern of damage which occurs. Several areas of the brain are affected but the brunt of the damage occurs in the basal ganglia especially the caudate and putamen nuclei, these are sometimes called the corpus striatum. There are complex connections between the areas of the brain: in the case of HD the direct and indirect pathways are important for understanding some of the physical features and why drugs which block the dopamine 2 receptors are used to treat chorea.

Ascorbic acid improves extrapyramidal syndromes and corpus striatal degeneration induced by dopamine-2 receptor inhibition in Wistar rats

ObjectivesThe prolonged uses of fourth-generation antipsychotics have been implicated in inducing extrapyramidal syndromes characterized by the motor deficit. This was attributed to the loss of dopamine-2 receptor (D2R) signaling. However, ascorbic acid (SVCT2R stimulation) in the brain is proposed to modulate D2R activity. We, therefore, investigated the beneficial roles of ascorbic acid in improving the extrapyramidal symptoms seen in D2R loss.MethodsTwenty adult male Wistar rats of average weight 200 g were distributed randomly into four groups. The control (NS) received normal saline for 28 days, Untreated D2R inhibition group (−D2R) received normal saline for seven days and then subsequently received chlorpromazine for 21 days, D2R inhibition group treated with ascorbic acid (−D2R+SVCT2R) received chlorpromazine for 21 days and was subsequently treated with ascorbate for seven days while the withdrawal group (WG) received chlorpromazine for 21 days and subsequently received normal saline for seven days. Motor deficits were assessed using a rotarod and cylinder test. The corpus striatum was harvested, processed, and stained using H&E and Nissl stains. Cellular density was analyzed using Image J software 1.8.0.ResultsMotor deficit was observed in −D2R animals administered chlorpromazine with less improvement in WG compared to control (p<0.05) in both rotarod and cylinder test. Ascorbic acid (SVCT2R stimulation) significantly (p<0.001) improved the latency of fall and climbing attempts observed in −D2R animals. The density of basophilic trigoid bodies was significantly (p<0.001) restored in −D2R+SVCT2R group, suggesting recovery of neural activity in the corpus striatum. Moreover, the hallmarks of neuronal degeneration were less expressed in the ascorbic acid treatment groups.ConclusionsAscorbic acid putatively ameliorates extrapyramidal symptoms observed in D2R blockage by chlorpromazine in Wistar rats.

Role of caloric vestibular stimulation in improvement of motor symptoms and inhibition of neuronal degeneration in rotenone model of Parkinson's disease – An experimental study

ObjectiveParkinson's disease (PD) is a progressive neurodegenerative disorder. In order to explore a noninvasive treatment of PD, in the current study the authors evaluated the neuroprotective efficacy of caloric vestibular stimulation (CVS) using the rotenone-induced rat model of PD. The rotenone models of PD are gaining attention due to high reproducibility. It is also considered to be an improved model to exhibit the pathogenesis of PD and test the neuroprotective effect of various therapeutic interventions.Materials and methodsRotenone was i.p. injected (3 mg/kg body weight) to male Wistar albino rats for 21 days to induce PD. As PD is chronic and progressive in nature, the efficacy of chronic CVS intervention was evaluated for 30 days after inducing PD in rats. Motor symptoms were evaluated by assessing locomotor activity in actophotometer, whereas movement analysis was done using Ludolph test and motor coordination was evaluated using rotarod apparatus. The neurochemical and neuropathological changes were also observed in the corpus striatum of rats.ResultsRotenone administration showed decreased locomotor activity, motor coordination and general movement associated with significant (P < 0.05) reduction in dopamine content in the corpus striatum. The immunohistochemical analysis revealed a marked decrease in tyrosine hydroxylase (TH) immunoreactivity in striatal neurons indicating the significant loss of dopaminergic neurons in substantia nigra (SN) following rotenone injection. However, chronic treatment with CVS restored the nerve terminals in the striatum from rotenone damage. CVS treatment improved the dopaminergic system function by restoring dopamine content in the striatum. CVS also improved the motor deformities clearly suggesting the neuroprotective function.ConclusionThe results of the present study suggested CVS to be a safe and simple neuroprotective measure against neurodegenerative changes in PD and a promising noninvasive technique to overcome the motor symptoms associated with it. The findings could be useful for further investigations and clinical applications of CVS in the treatment of PD.