Effects of cloperastine, a non-narcotic antitussive, on the expression of GIRK channels in the brain of methamphetamine-induced hyperactive mice

Objectives: Centrally-acting antitussives with inhibitory effects on G protein-coupled inwardly rectifying potassium (GIRK) channels have been shown to also inhibit methamphetamine-induced hyperactivity in mice. In this study, we examined if cloperastine, which is the most potent inhibitor of the GIRK channels among antitussives, is sensitive to the expression levels of GIRK channels in the brain of methamphetaminetreated mice. Materials and Methods: The brain tissues have been removed and the total RNA has been extracted from tissues. The mRNA levels were evaluated using semiquantitative reverse transcription-polymerase chain reaction. Results: The concentration levels of the mRNA of GIRK channels within the ventral midbrain of methamphetamine-treated mice increased as compared with that in control and cloperastine reduced an upregulation in GIRK2, one of the subunits of the GIRK channels, by the injection of methamphetamine. Conclusion: These findings suggest that cloperastine might ameliorate hyperactivity by inhibiting the GIRK channels in the brain.

Dorsal midbrain syndrome from thalamocapsuloganglionic hemorrhage: A case report

@#Dorsal midbrain syndrome (DMS) is a supranuclear palsy of vertical gaze characterized by conjugate upgaze palsy, light-near dissociation, convergence-retraction nystagmus, lid retraction, and skew deviation. Majority of cases are due to primary midbrain lesions such as strokes or neoplasms, or due to pineal gland tumors compressing the said area. Presented here is the case of a 57-year-old male who came in with a chief complaint of diplopia and the typical signs of DMS. Cranial tomography scan revealed a parenchymal hemorrhage at the left thalamocapsuloganglionic region, a rarely reported site of a primary lesion causing DMS. In this case, the syndrome may have been a consequence of the mass effects and perilesional edema associated with the thalamocapsuloganglionic hemorrhage, or may have been due to disruption of supranuclear inputs to the dorsal mibdrain. This case provides further evidence that DMS may arise from lesions without obvious involvement of the said region. This case also highlights the importance of a thorough physical examination to elicit the findings associated with DMS, and the need to correlate these with a keen analysis of diagnostic test results.

A Deep Mesencephalic Nucleus Circuit Regulates Licking Behavior / 神经科学通报·英文版

Licking behavior is important for water intake. The deep mesencephalic nucleus (DpMe) has been implicated in instinctive behaviors. However, whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown. Here, we found that the activity of the DpMe decreased during water intake. Inhibition of vesicular glutamate transporter 2-positive (VGLUT2+) neurons in the DpMe resulted in increased water intake. Somatostatin-expressing (SST+), but not protein kinase C-δ-expressing (PKC-δ+), GABAergic neurons in the central amygdala (CeA) preferentially innervated DpMe VGLUT2+ neurons. The SST+ neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior. Activation of these CeA SST+ GABAergic neurons, but not PKC-δ+ GABAergic neurons, projecting to the DpMe was sufficient to induce licking behavior and promote water intake. These findings redefine the roles of the DpMe and reveal a novel CeASST-DpMeVGLUT2 circuit that regulates licking behavior and promotes water intake.

Clinical analysis of 4 cases of Wernekink commissure syndrome / 中南大学学报(医学版)

Wernekink commissure syndrome (WCS) is very rare. Four patients with WCS, admitted to our hospital from April to May 2018, were chosen for this study, and their clinical manifestations, imaging features, and etiology were retrospectively analyzed based on the literatures. All patients with WCS manifested as bilateral cerebellar ataxia such as symmetrical limb and trunk ataxia, but the degree of ataxia was asymmetrical distribution based on the anatomy. Dysarthria was the main and constant clinical manifestation of the syndrome. Ophthalmoplegia had great variability, and WCS with oculomotor nerve palsy may be considered as atypical WCS. The incidence of olivary degeneration and palatine myoclonus is relatively low, which may be related to the difference in the reported time intervals of cases. Changes in consciousness and emotion may be the characteristic of neglected WCS, which should be paid more attention. Cerebral infarction is the main etiology of WCS. We reported that cerebral infarction and WCS was the first symptom in a patient with systemic lupus erythematosus (SLE). We should pay more attention to special etiology in diagnosis and treatment of WCS.

Acute isolated medial rectus palsy due to infarction as a result of hypercoagulable state: A case report and literature review

Isolated medial rectus palsy in an otherwise healthy individual is a very rare entity. However, this may point towards underlying systemic pathology. This is a case report of an otherwise healthy young adult male who presented with sudden onset non-progressive blurring of vision in right eye. A series of investigations were performed and the patient was diagnosed to have a rheumatological disorder. Isolated muscle palsies in young patient may be masking a systemic disorder and needs to be evaluated thoroughly.

InfarctionofthearteryofPercheron:5casesandliteraturereview / 实用放射学杂志

Objective Toanalyzetheimagingcharacteristicsandearlydiagnosticvalueofpatientswithinfarctionofthearteryof Percheron(AOP).Methods Theclinicaldataandimagingfeaturesof5patientswithAOPinfarctionwereanalyzedretrospectively, andrelevantliteratures werereviewed.Results Allof5patientspresented withdisturbanceofconsciousness.MRIof5patients showedsymmetricalhighsignalonDWIinthebilateralparamedianthalami,and1patientwithanteriorthalamiclesionand1patient withmidbrainlesionshowed "V"sign.Inaddition,MRAshowedlocalizedstenosisoftheP1segmentoftheposteriorcerebralartery in2patients.Conclusion TheclinicalpresentationsofpatientswithAOPinfarctionarevariable.Thesymmetricalhighsignalinthe bilateralparamedianthalamionDWIishelpfulforearlydiagnosisandclinicaltreatmentofAOPinfarction.

The effect of activation of P2X7 receptor on Ca2+ level in lateral midbrain periaqueductal gray neuron / 医学研究生学报

Objective The main intracellular signal of P2X7 receptor activation is the increasing of Ca2+, which then presents the diversity of its physiological and pathological functions through multiple intracellular signal transduction. To observe the effect of activation of P2X7 receptor on intracellular calcium（Ca2+）level in lateral midbrain periaqueductal gray (lPAG) neurons of primary cultured rat. Methods The primary cultured lPAG neurons were randomly divided into 4 groups: control group(no drug added), only for control; BzATP group(100 μmol/L); A-740003+ BzATP group(incubate with 100 nmol/L A-740003 for 10 min, then add 10 μmol/L ofBzATP); BzATP control group(add in Ca2+-free solution for 20 min, then add BzATP). The incubation solution of control group, BzATP group and A-740003+ BzATP group are DMEM/F12 medium, and the BzATP control group is Ca2+-free. The laser scanning confocal microscopy (LSCM) was used to detect : the changes of cultured neuron Ca2+ levels by different concentrations of BzATP; the effects of A-740003 and Ca2+-free medium preincubation on BzATP-induced Ca2+ level alterations in cultured neurons. Results BzATP dose-dependently increased the Ca2+ levels in cultured lPAG neurons; A-740003 and Ca2+-free medium inhibited the BzATP-induced increasing of Ca2+ level in cultured lPAG neurons. LSCM showed: The intracellular calcium fluorescence insensity(2.48±1.05) in the BzATP group was significantly higher than that in the blank control group, BzATP control group and A-740003+ BzATP group[(1.12±0.03), (1.09±0.03), (1.14±0.08)](P<0.01). Conclusion The activation of P2X7 receptor can increase the level of lPAG neurons Ca2+ , and is associated with the extracellular Ca2+ influx.

Unique case of midbrain tuberculoma presenting as isolated inferior rectus palsy with nystagmus

Isolated brain stem tuberculoma constitutes about 5% of all intracranial tuberculomas. A case of isolated inferior rectus palsy with downbeat nystagmus due to presumed midbrain tuberculoma in an immunocompetent patient is described here. This report documents a rare entity of a combination of partial third nerve palsy with pupil involvement along with downbeat nystagmus.

Analysis of clinical features of brainstem encephalitis manifested as Parkinson syndrome / 中国神经精神疾病杂志

Objective To analyze the clinical manifestations and imaging features of human brainstem encephalitis with Parkinson syndrome as the main manifestations. Methods Combined with related literature, the clinical, laboratory and imaging features of three patients with brainstem encephalitis, which were mainly manifested as Parkinson syndrome, were analyzed. Results The 3-hour video EEG showed normal in 2 cases and abnormal in one case with more delta wave in each leads. Cerebrospinal fluid examination revealed normal cell numbers in one case, increased cell numbers in 2 case and elevated cerebrospinal fluid proteins in all 3 cases. serum and CSF IgG anti-NMO antibodies as well as autoimmune encephalitis antibodies were negative in 3 cases. Brain MRI showed symmetrical abnormal signal in bilateral midbrain and pia mater enhancement increased in 3 cases. After hormone, and madopar treatment, Parkinson syndrome symptoms were significantly improved in two patients. Conclusion Brainstem encephalitis-induced symmetrical midbrain lesion can manifest as Parkinson syndrome. The laboratory tests reveal an involvement of immune system and hormone therapy may be effective.

Clinical symptoms and etiological classification in patients with isolated midbrain infarction / 中国脑血管病杂志

Objective To investigate the clinical manifestations,imaging features,and etiological classification in patients with isolated midbrain infarction. Methods From December 2013 to January 2017,40 consecutive patients with isolated midbrain infarction admitted to the Department of Neurology, General Hospital of Shenyang Military Command were enrolled retrospectively. The general data,clinical and imaging data of the patients were analyzed retrospectively. According to the vascular control range and MRI characteristics,the midbrain infarcts were divided into anteromedial,anterolateral,lateral and dorsal infarcts . The differences of baseline data,clinical manifestation and etiological typing of various types of patients were analyzed. Results In the 40 patients,23 were anteriomedial infarction,14 were anterolateral infarction, 1 was lateral infarction,and 2 were mixed location infarction,0 was dorsal infarction. The common signs were dysarthria in 23 cases (57. 5%),limb and／or gait ataxia in 18 cases (45. 0%),oculomotor disturbances and／or ptosis in 15 cases (37. 5%),and limb movement disorders in 14 cases (35. 0%). The differences were statistically significant in central facial paralysis and／or lingual paralysis (3／23 vs. 8／17 ),oculomotor disturbances (15／23 vs. 0 ),and etiological types between the patients with anterior medial infarction and those infarction at other sites (all P＜0. 05). Of the 40 patients,38 had a short-term good prognosis (95. 0%)and 2 had poor prognosis (5. 0%). Conclusions Isolated midbrain infarcts mainly manifested as dysarthria,ataxia,and oculomotor disturbances. Oculomotor disturbances occurred in anteromedial infarction. The common causes of anteromedial infarction are large atherosclerosis and small vascular lesions,while the cause of infarction in other sites is often large atherosclerosis.

Descripción de cambios en la difusibilidad media en resonancia magnética por lesiones del sistema reticular activador ascendente en pacientes adultos con trauma craneoencefálico y alteración del estado de conciencia / Description of changes in mean diffusivity in magnetic resonance of injuries of the ascending reticular system in patients with traumatic brain injury and impaired consciousness

RESUMEN INTRODUCCIÓN: Los pacientes con trauma craneoencefálico severo pueden tener secuelas neurológicas graves que generan discapacidad de rangos diferentes según la escala de Barthel. La alteración del estado de consciencia es la secuela más grave y es causa de dependencia completa de estos pacientes por la pérdida del autocuidado. La relación entre los hallazgos anormales en las neuroimágenes y los diferentes estados de conciencia ha sido objeto de investigación en los últimos años, con la posibilidad de que existan nuevas opciones con el posproceso de imágenes obtenidas por resonancia magnética nuclear. Este estudio pretende describir las alteraciones en la difusibilidad media haciendo posproceso en la secuencia de DWI en 4 pacientes con trauma craneoencefálico severo y alteración del estado de consciencia, quienes en la fase aguda del trauma fueron estudiados con imágenes convencionales de tomografía y resonancia. MATERIALES Y MÉTODOS: Se describe una serie de 4 casos de pacientes con trauma craneoencefálico severo y alteración del estado de consciencia a quienes se realizó resonancia cerebral simple. Las imágenes fueron sometidas a un posproceso de la secuencia de DWI analizando diferentes regiones por donde transcurren las fibras del sistema reticular activador ascendente (SRAA) (cuerpos restiformes, rafe medio del mesencéfalo, tálamo, regiones subinsulares y lóbulos frontales basales). Igualmente se tomaron valores de difusibilidad en regiones similares, en 5 sujetos sin alteración estructural cerebral tomados como controles. RESULTADOS: Se encontró disminución en la difusibilidad media en las diferentes regiones establecidas en el estudio, que tuvieron diferente localización en cada paciente. Los valores disminuyeron aproximadamente en un 50 % respecto a los del grupo control, observando lesiones en áreas que no fueron identificadas en la interpretación de la imagen cuando fue adquirida durante el trauma. CONCLUSIONES: El posproceso de la secuencia DWI muestra disminución en los valores de difusibilidad media en regiones por donde transcurren las vías del sistema reticular activado ascendente, estos cambios que explican las diferentes alteraciones en el estado de conciencia, no fueron visualizados en las imágenes interpretadas bajo las técnicas convencionales. Se requiere nuevos estudios para establecer las características operativas de la prueba que permitan definir su potencial utilidad dentro de los algoritmos de clasificación inicial de los pacientes con trauma craneoencefálico severo.

SUMMARY INTRODUCTION: Patients with severe traumatic brain injury may have severe neurological sequelae that generate disability of different ranges, according to the Barthel scale. The consciousness impairment is the most serious sequela and is a cause of complete dependence of these patients, due to the loss of self-care. The relationship between abnormal findings in neuroimaging and different states of consciousness has been the subject of research in recent years, with the possibility of new options with the post-processing of magnetic resonance imaging (MRI). This study aims to describe the alterations in the mean diffusivity by post-processing of the diffusion weighted imaging (DWI) sequence in 4 patients with severe traumatic brain injury and impairment of consciousness, who were studied with computed tomography (CT) and MRI in the acute phase of the trauma. MATERIALS AND METHODS: We describe a series of 4 cases of patients with severe traumatic brain injury and impaired consciousness in whom a non-enhanced brain MRI was performed. The DWI sequence images were post-processed, analyzing different regions through which the fibers of the Ascending Reticular Activating System (ARAS) (including restiform bodies, midbrain, thalamus, sub-insular regions and basal frontal lobes) pass. Likewise, diffusivity values were taken in similar regions, in 5 subjects without any structural brain abnormality, who were taken as controls. RESULTS: There was a decrease in mean diffusivity in the different regions established in the study, which had different locations in each patient. Values decreased approximately 50 percent from values in normal patients. After post-processing, some lesions were observed in areas that were not identified in the initial MRI interpretation during the trauma. CONCLUSIONS: The post-processing of the DWI sequence shows a decrease in the mean diffusivity values in regions where the ARAS pathways pass through. These changes explaining the different alterations in consciousness were not visualized in the images interpreted under conventional MRI techniques. New studies are required to establish the operative characteristics of this test, that allow to define its potential utility within the algorithms of initial classification of patients with severe traumatic brain injury.

Research on effect of midbrain VTA dopaminergic neurons in general anesthesia / 重庆医学

Objective To investigate the effect of dopaminergic neurons of midbrain ventral tegmental area(VTA) in general anesthesia.Methods Forty adult healthy male SD rats were randomly divided into lesion group (n=20) and control group (n=20).The lesion group was given the bilateral infusion of specific dopaminergic neuron injury agent 6-OHDA in midbrain lateral VTA,while the control group received the same volume of normal saline at the same areas.The time of loss of righting reflex (LORR)loss and recovery of righting reflex(RORR)at postoperative 2 week were observed in each group.Results Compared with the control group,the LORR time in the lesion group was shortened and the RORR time was significantly prolonged under propofol-induced anesthesia (P＜0.05).However,the LORR time under the isoflurane anesthesia had no statistically significant difference between the two groups(P＞0.05),while the RORR time in the lesion group was increased(P＜0.05).Conclusion Dopaminergic neurons in midbrain VTA might play different roles in the induction and recovery of different general anesthetics.

Vertical One-and-a-Half Syndrome Accompanying Contralateral Abduction and Incomplete Depression Palsy Due to Thalamo-Mesencephalic Infarction / 대한평형의학회지

Vertical gaze palsy is usually associated with lesions of the rostral midbrain and thalamo-mesencephalic junction. The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), the interstitial nucleus of Cajal, and the posterior commissure located in the midbrain are the critical area in supranuclear control of vertical eye movements. We describe a case of vertical one-and-a-half syndrome accompanying contralateral abduction and incomplete depression palsy due to thalamo-mesencephalic infarction. These vertical eye movement abnormalities are presumed to be caused by damage to the ipsilateral riMLF, interstitial nucleus of Cajal, and oculomotor fascicles.

Functional Neuroanatomy for Posture and Gait Control

Here we argue functional neuroanatomy for posture-gait control. Multi-sensory information such as somatosensory, visual and vestibular sensation act on various areas of the brain so that adaptable posture-gait control can be achieved. Automatic process of gait, which is steady-state stepping movements associating with postural reflexes including headeye coordination accompanied by appropriate alignment of body segments and optimal level of postural muscle tone, is mediated by the descending pathways from the brainstem to the spinal cord. Particularly, reticulospinal pathways arising from the lateral part of the mesopontine tegmentum and spinal locomotor network contribute to this process. On the other hand, walking in unfamiliar circumstance requires cognitive process of postural control, which depends on knowledges of self-body, such as body schema and body motion in space. The cognitive information is produced at the temporoparietal association cortex, and is fundamental to sustention of vertical posture and construction of motor programs. The programs in the motor cortical areas run to execute anticipatory postural adjustment that is optimal for achievement of goal-directed movements. The basal ganglia and cerebellum may affect both the automatic and cognitive processes of posturegait control through reciprocal connections with the brainstem and cerebral cortex, respectively. Consequently, impairments in cognitive function by damages in the cerebral cortex, basal ganglia and cerebellum may disturb posture-gait control, resulting in falling.

Protective effect of protocatechuic acid on midbrain dopaminergic neurons injured by 1-methyl-4-phenylpyridinium / 中草药

Objective: To investigate the effects of protocatechuic acid (PCA) on the midbrain dopaminergic neurons injured by 1-methyl-4-phenylpyridinium (MPP+). Methods: Midbrain neuron cells from KM mice pregnant 14 d were used in this experiment, and divided into control group, model group, low-, mid-, and high-dose (0.05, 0.1, and 0.5 mmol/L) groups. MTT method was used to determine the neuronal survival rate. The activity of lactate dehydrogenase (LDH) in culture, content of intracellular reactive oxygen species (ROS), activity of mitochondrial complex I, and mitochondrial membrane potential were further determined. Results: PCA can enhance the viability of dopaminergic neurons damaged by MPP+, reduce the release of LDH and the generation of ROS, increase the activity of the mitochondrial complex Ι, and prevent the reduction of mitochondrial membrane potential. Conclusion: PCA has the neroprotective effects against MPP+-induced damage of midbrain dopaminergic neurons.

Anesthetic experience of Benedikt syndrome complicating lumbar spine involved multiple myeloma: A case report

Benedikt syndrome is characterized by ipsilateral ophthalmoplegia with contralateral hemichorea due to a midbrain lesion. A 67-year-old male with Benedikt syndrome underwent corpectomy at L1 and anterolateral interbody fusion at T12-L2 due to pathologic bursting fracture at L1 involving multiple myeloma. He had a history of traumatic subarachnoid hemorrhage and subdural hemorrhage 8 months before surgery. Magnetic resonance image of the brain revealed intracranial hemorrhage from thalamus to midbrain. Target controlled infusion with propofol and remifentanil were administered for anesthetic induction and maintenance and close hemodynamic and neurologic monitoring led to successful anesthetic management.

Proteomic analysis of energy metabolism-related proteins of mice midbrain / 国际检验医学杂志

Objective To identify energy metabolism-proteins of mice midbrain by using the proteomic technique,and to investi-gate the relationship between these proteins and neural diseases.Methods Two-dimensional gel electrophoresis was used to sepa-rate totally soluble proteins extracted from mice midbrain.Some protein spots on two-dimensional gel electrophoresis gels were ana-lyzed by using matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).Results 24 protein spots related with energy metabolism were separated by two-dimensional gel electrophoresis and identified by using MALDI-TOF MS successfully.Conclusion The establishment of energy metabolism-related proteins map of mice midbrain lays a foundation for the research on the involvement of these proteins in neural disease pathogenesis.

Micrographia after Midbrain Tegmental Infarction

Micrographia is an abnormal reduction in writing size that is a specific behavioral deficit associated with Parkinson's disease. A 24-year-old right-handed woman presented with sudden-onset right-hand micrographia. Brain magnetic resonance imaging revealed an infarction of the right tegmentum of the lower midbrain. The mechanism of micrographia caused by pure midbrain tegmental infarction remains unclear. This case could provide evidence of the functional anatomy of a direct connection between the cerebellum and basal ganglia through the midbrain.

The evaluation of 3D-CISS sequence in diagnosis of midbrain aqueduct obstruction / 实用放射学杂志

Objective To explore the value of three-dimensional constructive inference in steady state sequence (3D-CISS se-quence)in case of midbrain aqueduct obstruction.Methods 46 cases with midbrain aqueduct obstruction were scanned with FLASH T1 WI、TSE T2 WI and 3D-CISS sequence at 3.0T superconductive MR scanner.The original images of the 3D-CISS sequence were reconstructed.The images of three sequences showing midbrain aqueduct obstruction were observed and analyzed.Results The de-tection rate of the midbrain aqueduct obstruction was 13% 、71.7% and 100% in FLASH T1 WI、TSE T2 WI and 3D-CISS sequence, respectively.The difference between the three sequences were significant (P <0.01 67).Conclusion 3D-CISS sequence shows mid-brain aqueduct obstruction more accurately.

Holmes' Tremor Associated with Bilateral Hypertrophic Olivary Degeneration Following Brain Stem Hemorrhage: A Case Report

Holmes' tremor is a condition characterized by a mixture of postural, rest, and action tremors due to midbrain lesions in the vicinity of the red nucleus. Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration involving the dento-rubro-olivary pathway and may present clinically as Holmes tremor. We report on a 59-year-old female patient who developed Holmes tremor in association with bilateral HOD, following brain stem hemorrhage.