Quantitative susceptibility mapping of the substantia nigra subregions in relapsing-remitting multiple sclerosis patients / 中华放射学杂志

Objective:To investigate the distribution of iron deposition in the substantia nigral (SN) subregions on quantitative susceptibility mapping (QSM) and the change of swallow tail sign (STS) in patients with relapsing-remitting multiple sclerosis (RRMS) of different disease stages.Methods:The clinical and imaging data of 53 patients with RRMS (case group) diagnosed at the First Hospital of Chongqing Medical University from November 2019 to December 2021 were retrospectively analyzed. The case group was divided into 0-5 years subgroup, 6-10 years subgroup, and >10 years subgroup according to the disease duration; another 37 age-and gender-matched healthy volunteers were recruited as the control group during the same period. All subjects underwent MRI and QSM reconstruction. First, the SN was divided into four subregions: rostral anterior-SN (aSNr), rostral posterior-SN (pSNr), caudal anterior-SN (aSNc), and caudal posterior-SN (pSNc) on the QSM, and the quantitative susceptibility value (QSV) of each subregion was measured, and then the STS of the SN was observed and scored on the susceptibility weighted imaging (SWI) generated by post-processing. ANOVA was used to compare the differences in the QSV of each subregion of SN among the groups, and the probability of abnormal STS was compared using the χ 2 test. Spearman′s test was used to analyze the correlation between the QSV of each subregion of SN and the STS score. Results:The differences in QSV of aSNr, pSNr, aSNc, and pSNc were statistically significant among the 0-5 years subgroup, 6-10 years subgroup,>10 years subgroup of RRMS patients and the control group ( P<0.05). The QSV of aSNr, pSNr, and aSNc in 0-5 years subgroup was higher than those in the control group ( P was 0.039, 0.008, 0.039, respectively). The QSV of aSNr, aSNc, and pSNc in the 6-10 years subgroup were higher than those in the 0-5 years subgroup ( P was <0.001, 0.020, 0.015, respectively). The QSV of the aSNc, pSNc in >10 years subgroup were lower than those in the 6-10 years subgroup ( P=0.037, 0.006). The QSV of aSNr, pSNr in >10 years subgroup were higher than those in the control group ( P was <0.001, 0.001). There were 7 cases of abnormal STS in the 0-5 years subgroup, 11 cases in the 6-10 years subgroup, 12 cases in >10 years subgroup, and 9 cases in the control subgroup, and there was a statistically significant difference in the probability of abnormal STS among the subgroups of the RRMS patients and the control subgroup (χ 2=16.20, P=0.011). Both the scores of STS in the 6-10 years subgroup and >10 years group were positively correlated with the QSV in pSNc ( r s=0.65, P=0.006; r s=0.48, P=0.045). Conclusions:In RRMS patients, SN iron deposition is concentrated on aSNr, pSNr, and aSNc in the 0-5 years subgroup and on aSNr, aSNc and pSNc in the 6-10 years subgroup. The QSVs of all SN subregions have a downward trend in >10 years subgroup compared with that in the 6-10 years subgroup. Both the QSVs of the pSNc in the 6-10 years group and >10 years group are positively related to STS scores. These help explore the potential progression pattern of SN iron deposition in RRMS patients and the cause of abnormal STS in RRMS patients.

Transcranial sonography image characteristics of substantia nigra in different Parkinson′s disease subtypes and their correlation with iron metabolism / 中华超声影像学杂志

Objective:To explore the pathological mechanism of SN hyperechogenicity by investigating the characteristics of substantia nigra (SN) hyperechogenicity on transcranial sonography (TCS) and serum iron metabolism parameters in the postural instability gait difficulty and tremor dominant subtypes of Parkinson′s disease (PD), and the correlation between them.Methods:A total of 155 PD patients recruited in Parkinson′s Disease Specialty in the Second Affiliated Hospital of Soochow University from January 2019 to December 2021 were divided into postural instability gait difficulty group( n=95) and tremor dominant group( n=60). Meanwhile, 49 healthy gender- and age-matched healthy individuals who sought for physical examination during the same period were included as the control group. All subjects underwent TCS and blood test, and the echo of SN between the postural instability gait difficulty group and tremor dominant group, serum iron metabolism parameters among the three groups were compared. The postural instability gait difficulty group and tremor dominant group were subdivided into with SN hyperechogenicity (SN+ )subgroup and without SN hyperechogenicity (SN-) subgroup respectively according to TCS results, and the differences in serum iron metabolism parameters between the subgroups were further compared. The association between SN hyperechogenicity and serum iron metabolism parameters of the postural instability gait difficulty group and tremor dominant group were further analyzed. Results:The total area of bilateral SN+ , the area of SN+ on the larger side, and the ratio of the total area of SN+ to the midbrain area (S/M) in postural instability gait difficulty group were larger than those in tremor dominant group (all P<0.001). The value of serum ceruloplasmin and transferrin in both postural instability gait difficulty group and tremor dominant group were lower than those in control group (all P<0.001), and compared with tremor dominant group and control group, the postural instability gait difficulty group had lower serum ferritin(all P<0.01). In both postural instability gait difficulty group and tremor dominant group, serum ceruloplasmin in SN+ subgroup was lower than that in SN-subgroup ( P=0.001, 0.032). Moreover, there was a negative correlation between serum transferrin and the area of SN hyperechogenicity in two subgroups(postural instability gait difficulty group: rs=-0.454, P<0.001; tremor dominant group: rs=-0.494, P<0.001). Conclusions:Compared with the tremor dominant patients, the postural instability gait difficulty patients have larger area of SN hyperechogenicity and lower serum ferritin level. The area of SN hyperechogenicity is significantly negatively correlated with serum transferrin level, indicating that the production of this imaging characteristics is related to iron metabolism.

Glutamatergic Neurons in the Caudal Zona Incerta Regulate Parkinsonian Motor Symptoms in Mice / 神经科学通报·英文版

Parkinson's disease (PD) is the second most common and fastest-growing neurodegenerative disorder. In recent years, it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal ganglia are also related to PD pathogenesis. However, little is known about whether and how the caudal zona incerta (ZIc) regulates parkinsonian motor symptoms. Here, we showed that specific glutamatergic but not GABAergic ZIc

Effect of astragaloside IV on PI3K/Akt signaling pathway in substantia nigra of mice with Parkinson′s disease / 中华麻醉学杂志

Objective:To evaluate the effect of astragaloside IV on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in substantia nigra of mice with Parkinson′s disease.Methods:Forty-five SPF healthy male C57BL/6 mice, aged 8 weeks, weighing 19-25 g, were divided into 3 groups ( n=15 each) using a random number table method: control group (group C), Parkinson′s disease group (group PD) and astragaloside IV group (group A). The mouse model of Parkinson′s disease was developed by intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) 30 mg/kg everyday for 7 consecutive days.Astragaloside 20 mg/kg was intraperitoneally injected everyday at 30 min before MPTP injection for 7 consecutive days before the model was prepared in group A, and the equal volume of normal saline was given instead in group C. Behavior was measured at 1 day interval after completion of administration.The mice were then sacrificed, and the substantia nigra of the brain tissue were obtained for determination of the expression of tyrosine hydroxylase(TH), phosphorylated PI3K(p-PI3K), phosphorylated Akt(p-Akt), glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) (by Western blot). Results:Compared with C group, the total distance of movement and latency of falling were significantly shortened, the hanging score was decreased, the step width was increased, the expression of TH, p-PI3K, p-Akt and BDNF in substantia nigra was down-regulated, and the expression of GFAP was up-regulated in PD group and A group ( P<0.05). Compared with PD group, the total distance of movement and the latency to fall were significantly prolonged, the hanging score was increased, the step width was reduced, and the expression of TH, p-PI3K, p-Akt and BDNF in the substantia nigra was up-regulated, and the expression of GFAP was down-regulated in group A ( P<0.05). Conclusions:The mechanism by which astragaloside IV improves motor dysfunction is related to the activation of PI3K/Akt signaling pathway, up-regulation of BDNF expression and inhibition of astrocyte activation in mice with Parkinson′s disease.

Dyskinesia is Closely Associated with Synchronization of Theta Oscillatory Activity Between the Substantia Nigra Pars Reticulata and Motor Cortex in the Off L-dopa State in Rats / 神经科学通报·英文版

Excessive theta (θ) frequency oscillation and synchronization in the basal ganglia (BG) has been reported in elderly parkinsonian patients and animal models of levodopa (L-dopa)-induced dyskinesia (LID), particularly the θ oscillation recorded during periods when L-dopa is withdrawn (the off L-dopa state). To gain insight into processes underlying this activity, we explored the relationship between primary motor cortex (M1) oscillatory activity and BG output in LID. We recorded local field potentials in the substantia nigra pars reticulata (SNr) and M1 of awake, inattentive resting rats before and after L-dopa priming in Sham control, Parkinson disease model, and LID model groups. We found that chronic L-dopa increased θ synchronization and information flow between the SNr and M1 in off L-dopa state LID rats, with a SNr-to-M1 flow directionality. Compared with the on state, θ oscillational activity (θ synchronization and information flow) during the off state were more closely associated with abnormal involuntary movements. Our findings indicate that θ oscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1 θ oscillation may participate in the induction of dyskinesia.

Effects of propofol on inflammatory responses in substantia nigra in mice with Parkinson′s disease: relationship with α-syn expression / 中华麻醉学杂志

Objective:To evaluate the effects of propofol on inflammatory responses in substantia nigra in mice with Parkinson′s disease (PD) and its relationship with α-synuclein (α-syn) expression.Methods:Thirty-three SPF healthy male C57BL/6 mice, aged 12 weeks, weighing 24-26 g, were divided into 3 groups ( n=11 each) using a random number table method: control group (group Con), group PD and propofol group (group Pro). In PD and Pro groups, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) 30 mg/kg was intraperitoneally injected once a day for 5 consecutive days to induce PD.Propofol 50 mg/kg was intraperitoneally injected at 2 h after the last injection of MPTP in group Pro, while the equal volume of normal saline was given instead in Con and PD groups.The rotarod test was performed at 24 h after administration.The animals were then sacrificed and substantia nigra was removed for determination of contents of interleukin-1β (IL-1β) and tumor necrosis factor (TNF)-α (by enzyme-linked immunosorbent assay), the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and p-caspase-1 (by Western blot) and the expression of α-syn (by immunofluorescence staining). Results:Compared with Con group, the first fall-off time was significantly shortened, the number of falling off was increased, the contents of IL-1β and TNF-α were increased, and the expression NLRP3, p-caspase-1and α-syn was up-regulated in substantia nigra in group PD ( P<0.05). Compared with PD group, the first fall-off time was significantly prolonged, the number of falling off was decreased, the contents of IL-1β and TNF-α were decreased, and the expression NLRP3, p-caspase-1and α-syn was down-regulated in substantia nigra in group Pro ( P<0.05). Conclusion:Propofol can improve behaviors of the mice through inhibiting inflammatory responses in substantia nigra, and the mechanism is related to down-regulating the expression of α-syn.

Reinforcement omission effects in rats with bilateral lesions in the substantia nigra pars compacta and ventral tegmental area

Reinforcement omission effects (ROEs) are characterized by higher response rates after reinforcement omission than after reinforcement delivery. This pattern of behavior is interpreted in terms of motivational and attentional processes. Recent studies from our laboratory have shown that the amygdala, nucleus accumbens, and medial prefrontal cortex are involved in ROE modulation. Also, the literature has demonstrated a role of other areas such as substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) in processes related to surprising events, such as prediction error and presentation or omission of an event (exteroceptive stimulus and reinforcement). Since these structures send projections to areas related to ROE modulation such as the amygdala, nucleus accumbens, and prefrontal cortex, the objective of the present study was to determine whether the SNc and VTA also integrate the circuit involved in ROE modulation. Rats were trained on a fixed-interval 12 s with limited-hold 6 s signaled schedule of reinforcement (Pre-lesion training). After acquisition of stable performance, the rats received bilateral neurotoxic lesions of the SNc (Experiment 1) and VTA (Experiment 2). Following postoperative recovery, the rats were submitted to two refresher sessions (Post-lesion training). Subsequently, the training was changed from a 100 to a 50% schedule of reinforcement (Post-lesion testing). In both experiments, the results showed that there was no difference in performance between sham rats and rats with bilateral lesions of the SNc or the VTA.

The changes of transcranial sonography in end-stage renal disease with restless legs syndrome / 中华超声影像学杂志

Objective@#To discuss the neuroimaging characteristics of transcranial ultrasound in end-stage renal disease (ESRD) with restless legs syndrome.@*Methods@#Transcranial sonography (TCS) was performed in ESRD with restless legs syndrome (RLS+ group, n=41), ESRD without restless legs syndrome (RLS- group, n=57) and control group (n=47), who were enrolled in the Second Affiliated Hospital of Soochow University from January 2017 to December 2018. The differences of the neuroimaging characteristics of TCS in substantia nigra (SN), brainstem raphe (BR) and red nucleus(RN) among the three groups were analyzed.@*Results@#The rate of SN hypoechogenicity was significantly higher in RLS+ group (36.6%, 15/41) than that in RLS- group (19.3%, 11/57) and control group(8.5%, 4/47) (χ2=10.6, P<0.05). The rate of abnormal BR echogenicity was significantly higher in RLS+ group (34.1%, 14/41) and RLS- group (29.8%, 17/57) than that in control group(10.6%, 5/47) (χ2=7.7, P<0.05). The rate of RN hyperechogenicity was significantly higher in RLS+ group (51.2%, 21/41) than that in RLS- group (21.1%, 12/57) and control group (10.6%, 5/47) (χ2=19.8, P<0.05). Between RLS+ and RLS- groups, when SN, BR and RN were all of positive performance, the accuracy of diagnosing RLS+ reached 70% (7/10).@*Conclusions@#The echogenicity changes of SN, BR and RN on TCS could provide valuable neuroimaging information for the clinical diagnosis and treatment of ESRD with restless legs syndrome.

The changes of transcranial sonography in end‐stage renal disease with restless legs syndrome / 中华超声影像学杂志

Objective To discuss the neuroimaging characteristics of transcranial ultrasound in end‐stage renal disease ( ESRD ) with restless legs syndrome . Methods T ranscranial sonography ( TCS ) was performed in ESRD with restless legs syndrome ( RLS + group , n ＝ 41 ) ,ESRD without restless legs syndrome ( RLS － group , n ＝57) and control group ( n ＝47) ,w ho were enrolled in the Second Affiliated Hospital of Soochow University from January 2017 to December 2018 . T he differences of the neuroimaging characteristics of TCS in substantia nigra ( SN ) ,brainstem raphe ( BR) and red nucleus ( RN ) among the three groups were analyzed . Results T he rate of SN hypoechogenicity was significantly higher in RLS +group ( 36 .6% ,15/41) than that in RLS － group ( 19 .3% ,11/57) and control group( 8 .5% ,4/47) ( χ2 ＝10 .6 ,P＜0 .05) . T he rate of abnormal BR echogenicity was significantly higher in RLS + group ( 34 .1% , 14/41) and RLS － group ( 29 .8% ,17/57) than that in control group( 10 .6% ,5/47) ( χ2 ＝7 .7 , P ＜0 .05) . T he rate of RN hyperechogenicity was significantly higher in RLS + group ( 51 .2% ,21/41 ) than that in RLS － group ( 21 .1% ,12/57) and control group ( 10 .6% ,5/47) ( χ2 ＝19 .8 , P ＜0 .05 ) . Between RLS+and RLS － groups ,when SN ,BR and RN were all of positive performance ,the accuracy of diagnosing RLS+ reached 70% ( 7/10 ) . Conclusions The echogenicity changes of SN ,BR and RN on TCS could provide valuable neuroimaging information for the clinical diagnosis and treatment of ESRD with restless legs syndrome .

Neuroprotective Effects of Low-molecular-weight Chondroitin Sulfate on Dopaminergic Neurons in MPTP-induced Parkinson ’s Disease Model Mice / 中国药房

OBJECTIVE： To observe neuroprotective effects of low-molecular-weight chondroitin sulfate （CS） on dopaminergic neurons in Parkinson’s disease （PD） mice model induced by 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）. METHODS： C57BL/6 mice were randomly divided into control group， MPTP injury group， low-molecular-weight CS low-dose and high-dose groups （100， 400 mg/kg）. Control group and MPTP injury group were given constant volume of normal saline intragstrically， administration groups were given relevant medicine intragastrically， once a day， for consecutive 17 d. Since 11th day after medication， except for control group， other groups were given MPTP solution （20 mg/kg） intraperitoneally to induce PD model， once a day， consecutive 5 d. After last medication， behavioral changes of mice （10 mice in each group） were evaluated by rotary rod fatigue tester. The damage of dopamine neurons （the percentage of TH positive cell and the percentage of fluorescence intensity） in substantia nigra of mice （3 mice in each group） was detected by immunohistochemistry and immunofluorescence. The content of dopamine in striatum was determined by HPLC （6 mice in each group）. The changes of oxidant stress indexes （SOD， GSH-Px， MDA） in substantia nigra of mice were determined by chemical colorimetry （6 mice in each group）. RESULTS： Compared with control group， retention time of mice on rotating rods was shortened significantly in MPTP injury group； TH positive cells of substantia nigra were decreased significantly， fluorescence intensity was obviously weakened； the percentage of positive cells and fluorescence intensity， the content of dopamine in striatum， the activities of SOD and GSH-Px in substantia nigra were decreased significantly， while the content of MDA was increased significantly （P＜0.01）. Compared with MPTP injury group， retention time of mice on the rotating rods was prolonged significantly in low-molecular-weight CS groups， the number of TH positive cells was increased significantly in substantia nigra and fluorescence intensity was increased significantly； the percentage of positive cells， the percentage of fluorescence intensity and the content of dopamine in striatum were increased significantly， while above indexes of high-dose group were significantly longer or higher than those of low-dose group （P＜0.05 or P＜0.01）. The activities of SOD and GSH-Px in substantia nigra were increased significantly in low-molecular-weight CS groups， while the content of MDA in substantia nigra was decreased significantly in low-molecular-weight CS high-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Prophylactic administration of low-molecular-weight CS can relieve the damage of dopaminergic neurons in substantia nigra of PD model mice induced by MPTP in a dose-dependent manner， and increase the secretion of dopamine in striatum. The effect may be related to the inhibition of lipid peroxidation and the enhancement of antioxidant capacity of tissues.

Correlation of substantia nigra hyperecho with essential tremor and Parkinson disease / 中华全科医师杂志

Objective To investigate the correlation of substantia nigra hyperecho with essential tremor (ET) and Parkinson disease (PD).Methods The clinical data of 158 patients with ET or PD who underwent transcranial ultrasonography in Tongji Hospital from March 2016 to March 2018 were retrospectively analyzed.There were 35 patients with ET (ET group),113 patients with PD who had no previous history of ET (PD group),and 10 PD patients with previous history of ET (ET-PD group).And 58 healthy subjects served as controls (control group).The hyperechoic area of substantia nigra in different groups was compared.Results The hyperechoic areas of the substantia nigra were [0 (0,0)]cm2 (control group),[0.27(0,0.41)]cm2 (ET group),[0.33(0.21,0.40)]cm2 (ET-PD group) and [0.35(0.29,0.45)]cm2 (PD group);the differences between control group and ET group,between the ET group and PD group were statistically significant (Z=-5.24,P=0.01;Z=-3.09,P=0.02),and there were no significant difference between the ET group and ET-PD group,between ET-PD group and PD group (Z=-0.98,P=0.32;t=-0.98,P=0.33).The ratio of substantia nigra hyperechoic positive to negative in ET-PD group was 9.00 (9/1),while that in ET group was 0.94 (17/18) (OR=9.53,95％ CI:1.09-83.43,x2=3.91,P=0.04).Conclusion Substantia nigra hyperecho is an objective imaging indicator for patients with ET and PD,and has a certain differential value for their diagnosis.

Nigrosome-1 on susceptibility weighted imaging and its clinical relevance in Parkinson's disease / 中华神经科杂志

Objective To evaluate the imaging features of nigrosome-1 in Parkinson's disease (PD) with a 3 T scanner by susceptibility weighted imaging (SWI),and to explore its clinical relevance.Methods Thirty-two patients with primary PD diagnosed by neurologists were collected.Healthy controls matched to their age and gender were recruited during the same period (n=20).All subjects underwent routine brain magnetic resonance imaging (MRI) and sensitive weighted imaging (SWI).The SWI images of the subjects were evaluated to evaluate nigrosome-1 by blinded investigators.Then,the correlation between imaging features and clinical data was analyzed.Results In the PD group,21 cases of bilateral "absent swallow-tail sign",five cases of bilateral "indecisive swallow-tail sign",five cases of "absent swallow-tail sign" on one side and "indecisive swallow-tail sign" on the other side,and one case of bilateral "clear swallow-tail sign" were found.The course of the "absent swallow-tail sign" group (56 (54) months) was significantly longer than the "non-absent swallow-tail sign" group (18 (18) months;U=-2.47,P=0.01).The Hoehn-Yahr stage was significantly higher in the "absent swallow-tail sign" group (2.0 (0.5)) than in the "non-absent swallow-tail sign" group (1.5 (0.5),U=-2.21,P=0.03).There was also a statistically significant difference in the Unified Parkinson's Disease Rating Scale score (24 (8),13 (14)) between the two groups (U=-2.91,P=0.01).However,there were no statistically significant differences between the two groups in the Hamilton Depression Scale score (5 (2) vs 5 (7),U=-0.10,P=0.94) and the Hamilton Anxiety Scale score (3.0 (2.5) vs 3.0 (3.0),U=-0.02,P=1.00).Conclusion The images of nigrosome-1 by SWI are closely related to the severity of the condition and motor symptoms of patients with PD,which can reflect the severity of the disease.

Dramatic unilateral decrease in uptake via the dopamine transporter: Imaging in a patient with hemiparkinsonism following the lacunar stroke in substantia nigra

@#Vascular parkinsonism (VaP) is typically defined as having predominant lower body involvement, postural instability, less prominent rest tremor and little or no response to treatment with levodopa. In this study, we report a patient with VaP with clear demonstration of a dramatic unilateral decrease of radiotracer uptake in a 18F-FP-CIT-PET study. A 62-year-old right-handed woman was referred to the neurology department due to rest tremor and rigidity in the right hand, which began after undergoing resection surgery for a left acoustic neuroma 7 years prior. Brain MRI, taken at 1 year after surgery showed an ischemic stroke lesion in the left medial pons and the left substantia nigra. 18F-FP-CIT-PET revealed a marked reduction of radiotracer uptake in left striatum compared to that of the right. We treated the patient with 100 mg of levodopa, 200 mg of entacarpone and 25 mg of carbidopa. There was an improvement in bradykinesia and tremor, but the symptoms persisted, and there was no deterioration during 6 months of observation. After acoustic neuroma surgery, ischemic complications are uncommon, and even a small lesion in the nigrostriatal pathway can cause a hemiparkinsonism. If a patient experience sudden onset hemiparkinsonism, they should be carefully examined for lesions in the nigrostriatal pathways. Under these conditions, the 18F-FP-CIT-PET scan can enable visualization of a unilateral decrease and is a useful tool for diagnosis and differentiation from idiopathic Parkinson’s disease

Interleukin-4 Contributes to Degeneration of Dopamine Neurons in the Lipopolysaccharide-treated Substantia Nigra in vivo

The present study investigated the effects of interleukin (IL)-4 on dopamine (DA) neurons in the substantia nigra (SN) in vivo of lipopolysaccharide (LPS)-treated rat. Tyrosine hydroxylase immunohistochemistry showed a significant loss of nigral DA neurons at 3 and 7 day post-LPS. In parallel, IL-4 immunoreactivity was upregulated as early as 1 day, reached a peak at 3 day and remained elevated at 7 day post-LPS. IL-4 immunoreactivity was detected exclusively in microglia. IL-4 neutralizing antibody (NA) significantly increased survival of DA neurons in LPS-treated SN in vivo by inhibiting microglial activation and production of proinflammatory mediator such as IL-1β as assessed by immunihistochemical, RT-PCR and ELISA analysis, respectively. Accompanying neuroprotection are IL-4NA effects on decreased disruption of blood-brain barrier and astrocytes. The present data suggest that endogenously expressed IL-4 from reactive microglia may be involved in the neuropathological processes of degeneration of DA neurons occurring in Parkinson's disease.

The comparison of neurobehavioral changes and impaired locations between the mouse model of manganism and Parkinson’s disease / 中华劳动卫生职业病杂志

Objective@#To investigate the effect of manganese chloride (MnCl2) or 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) on the neurobehavioral and histopathology in C57BL/6 mice and provide evidence for the diagnosis, treatment and prevention of manganism.@*Methods@#Adult male C57BL/6 mice were treated with MnCl2 and MPTP respectively by intraperitoneal injection at the doses of 5, 10, 20mg Mn/kg and 30mg MPTP/kg. Controls were injected equivalent normal saline. All animals were administrated 5 times a week for 4 consecutive weeks and sacrificed after behavior tests on the fifth week. Balance ability, anxiety and depression level and cognitive function were tested respectively by vertical pole test, open field locomotion test and Morris swim task. The neuron pathological changes of striatum and substantia nigra were examined through HE-staining pathological section by using optical microscope.@*Results@#Compared with the control group, the high dose of MnCl2 reduced body weight obviously (P<0.01) . The results of vertical pole test showed that MnCl2 and MPTP lengthened the pole-climbing time and turnaround time. Open field locomotion test showed that movement distance, stand-up time and central field time were decreased after the exposure of MnCl2 or MPTP. In the Morris swim task, the escape latency time increased and the target quadrant activity time decreased significantly after the injection of MPTP as well as high-dose MnCl2, comparing with controls (P<0.05) . Moreover, the escape latency time of high dose MnCl2 prolonged prominently comparing with MPTP grou (P<0.05) . The results of histopathology showed that acidophilic changes elevated in MnCl2 and MPTP group, comparing with controls. Furthermore, in striatum the oxyphil cells number increased in MnCl2 high-dose group comparing with MPTP group (P<0.01) . On the contrary, there were more oxyphil cells in MPTP group comparing with MnCl2 groups in substantia nigra (P<0.01) .@*Conclusion@#Both manganese and MPTP can induce the impairment of dopaminergic neural system, but the symptons and injured location of manganism are inconsistent with PD models induced by MPTP.

Effects of treatment on ultrastructure of olfactory bulb and GFAP expression in mice with Parkinson's disease / 中国针灸

OBJECTIVE@#To observe the effects of treatment on the ultrastructure of olfactory bulb and the expression of substantia nigra glial fibrillary acidic protein (GFAP) in mice with Parkinson's disease (PD) induced by lipopolysaccharide (LPS), and to provide methods and evidence for early prevention and treatment of PD.@*METHODS@#Forty C57BL/6 male mice were randomly divided into a blank group, a model group, an electroacupuncture (EA) group and a medication group, 10 mice in each one. The mice in the model group, EA group and medication group were treated with 30-day nasal perfusion of LPS to establish PD model. From the first day of model establishment, the mice in the EA group were treated with electroacupuncture at bilateral "Yingxiang" (LI 20) and "Yintang" (GV 29) for 20 min, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. The mice in the medication group were treated with intraperitoneal injection of L-DOPA, 10 mg/mL, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. After treatment, the behavioristics changes were observed by using footprint analysis and swimming test score; the ultrastructure of olfactory bulb was observed by using transmission electron microscopy; the expression of GFAP in substantia nigra was measured by using western blot method.@*RESULTS@#① After model establishment, the mice in the model group, the EA group and medication group showed significant symptoms of quiver and fear of chill, and the BMI was significantly lower than that in the blank group (all 0.05). ③ After treatment, the footprint and swimming time in the model group were significantly lower than that in the blank group (both <0.01); the footprint and swimming time in the EA group and medication group were significantly higher than those in the model group (all <0.01).④ After treatment, compared with the blank group, the organelles and ultrastructure of olfactory bulb in the model group were significantly improved; the ultrastructure of olfactory bulb in the EA group was improved compared with that in the model group. ⑤ After treatment, the expression of substantia nigra GFAP in the model group was significantly higher than that in the blank group (<0.01); the expression of substantia nigra GFAP in the EA group and medication group was significantly lower than that in the model group (both <0.05).@*CONCLUSION@#The early treatment of can improve behavioral disorders in LPS-induced early PD mice, and the mechanism may be related to the regulation of olfactory disorders and the expression of GFAP in substantia nigra.

Volume Gain of Brainstem on Medication-Overuse Headache Using Voxel-Based Morphometry / 中华医学杂志(英文版)

<p><b>Background</b>Histopathology identified the anatomical and molecular abnormalities of brainstem nuclei in migraine patients. However, the exact whole brainstem structural changes in vivo have not yet been identified in medication-overuse headache (MOH) transformed from migraine. The aim of this study was to investigate the regional volume changes over the whole brainstem in the MOH patients using voxel-based morphometry (VBM) in vivo.</p><p><b>Methods</b>High-resolution three-dimensional structural images were obtained using a 3.0-Tesla magnetic resonance system from 36 MOH patients and 32 normal controls (NCs) who were consecutively recruited from the International Headache Center, Chinese People's Liberation Army General Hospital, from March 2013 to June 2016. VBM was used to assess the brainstem structural alteration in the MOH patients, and voxel-wise correlation was performed to evaluate the relationship with the clinical characteristics.</p><p><b>Results</b>The brainstem region with increased volume located in the left ventrolateral periaqueductal gray (MNI coordinate: -1, -33, -8), ventral tegmental area (MNI coordinate: 0, -22, -12), bilateral substantia nigra (MNI coordinate: -8, -16, -12, 9, -16, -12), and trigeminal root entry zone (MNI coordinate: -19, -29, -31; 19, -32, -29) in MOH patients compared with NCs. The headache visual analog scale score was positively related with the left rostral ventromedial medulla (RVM) (MNI coordinate: -1, -37, -56; cluster size: 20; r = 0.602) in the MOH patients.</p><p><b>Conclusions</b>The regional volume gain of brainstem could underlie the neuromechanism of impaired ascending and descending pathway in the MOH patients, and the left RVM volume alteration could imply the impaired tolerance of nociceptive pain input and could be used to assess the headache disability in the MOH patients.</p>

Secondary Degeneration of the Ipsilateral Thalamus and Substantia Nigra Following Cerebral Infarction in the Striatum

Secondary degeneration after ischemic stroke has been demonstrated by computed tomography and magnetic resonance imaging. We report a 77-year-old man with striatal infarction followed by multifocal degeneration that developed in a stepwise manner at the ipsilateral substantia nigra and thalamus on diffusion-weighted images obtained at 4 weeks, 6 weeks and 20 weeks after onset. We also review the underlying pathophysiology and its clinical meanings.

Effect of pinealectomy and gonadectomy on dopaminergic neurons of mesencephalon in Parkinson's disease model rats / 中华行为医学与脑科学杂志

Objective To investigate the effect of PX and GDX on dopaminergic neurons of mesencephalon in Parkinson's disease model rats.Methods Eighty male Wistar rats were randomly divided into five groups:NS,N+6-OHDA,PX+6-OHDA,GDX+6-OHDA and PX+GDX+6-OHDA group;16 rats in each group.60 days after operation,6-OHDA was injected into SNc and VTA in the right side of the mesencephalon.Mter 14 days,the rats were sacrificed.HE staining was used to observe the proliferation of glial cells.The number of astrocytes was observed by GFAP staining.The number of apoptotic cells was observed by TUNEL staining.Immunohistochemical staining (S-P Method) was used to detect the changes of TH-positive cells and fiber,apoptosis-related proteins Bax and Bcl2.Results (1) The numbers of proliferated glial cells in SNc and VTA were significantly increased according to the following sequence:NS,N+6-OHDA,PX + 6-OHDA,GDX+ 6-OHDA,and PX+GDX+6-OHDA (HE staining:Hc =280.178,P＜0.01;Hc =334.260,P＜0.01) (GFAP staining:Hc=367.081,P＜0.01;Hc=376.049,P＜0.01).(2) The numbers of apoptotic cells in SNc and VTA were significantly increased according to the following sequence:NS,N+ 6-OHDA,PX+ 6-OHDA,GDX+6-OHDA,and PX+GDX+6-OHDA (Hc =344.401,P＜0.01;Hc =326.198,P＜0.01).(3) The numbers of TH (+) cells in SNc and VTA were significantly decreased according to the following sequence:NS,N+6-OHDA,PX+ 6-OHDA,GDX+ 6-OHDA,and PX+GDX+ 6-OHDA (Hc =366.532,P＜ 0.01;Hc =372.565,P＜0.01).(4) The gray values of TH(+) positive cells and fiber in SNc and VTA were significantly increased according to the following sequence:NS,N+6-OHDA,PX+6-OHDA,GDX+6-OHDA and PX+GDX+ 6-OHDA (F=517.239,P＜ 0.01;F=526.758,P＜ 0.01).(5) Bax expression:weakly positive in NS group,positive in N+6-OHDA group,and strongly positive in remaining three groups;Bcl2 expression:weakly positive in each group.Conclusion PX and GDX significantly aggravate neurotoxicity of 6-OHDA.And GDX is greater than PX,while PX + GDX is strongest.

Expression of Phosphatidylinositol 3-Kinase, Protein Kinase B and Mammalian Target of Rapamycin in Substantia Nigra in Rats with Parkinson's Disease / 中国康复理论与实践

@#Objective To observe the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in substantia nigra in rats with Parkinson's disease (PD). Methods A total of 96 Sprague-Dawley rats were randomly divided into sham group, model group, PI3K inhibitor LY294002 group and mTOR inhibitor rapamycin group. Each group was divided into 4 days and 8 days subgroups after the model. PD model was established by injecting rotenone subcutaneously. The expres-sion of PI3K, p-Akt and p-mTOR in substantia nigra was detected with immunohistochemistry and Western blotting. Results Compared with the sham group, the expression of PI3K, p-Akt and p-mTOR increased in the model group (P<0.05), and was more in 8 days subgroup than in 4 days subgroup (P<0.05). Compared with the model group, the expression of p-Akt and p-mTOR reduced in the LY294002 group (P<0.05), while the expression of PI3K varied little (P>0.05);the expression of p-mTOR decreased in the rapamycin group (P<0.05), while the expression of PI3K and p-Akt varied little (P>0.05). Conclusion PI3K/Akt/mTOR signaling pathway is over activated in substantia nig-ra in rats with Parkinson's disease, which may play an important role in occurrence and development of the disease.