Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases.They also represent a potential source of transplanted cells for therapeutic applications.In vi...Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases.They also represent a potential source of transplanted cells for therapeutic applications.In vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal development.Emerging evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons feasible.Using SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic neurons.To obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of induction.This increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing neurons.We further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 staining.Thus,we have established three induction protocols for dopaminergic neurons.Based on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.展开更多
Objective To identify the protective effect of lipopolysaccharide （LPS） preconditioning against LPS-induced inflammatory damage in dopaminergic neurons of midbrain slice culture and the possible mechanisms. Methods ...Objective To identify the protective effect of lipopolysaccharide （LPS） preconditioning against LPS-induced inflammatory damage in dopaminergic neurons of midbrain slice culture and the possible mechanisms. Methods After cultured in vitro for 14 d, the rat organotypic midbrain slices were pretreated with different concentrations （0, 1, 3, 6 or 10 ng/mL） of LPS for 24 h followed by treatment with 100 ng/mL LPS for 72 h. The whole slice viability was detelmined by measurement of the activity of lactic acid dehydrogenase （LDH）. Tyrosine hydroxylase-immunoreactive （TH-IR） neurons and CD 1 1 b/c equivalent-immunoreactive （OX-42-IR） microglia in the slices were observed by immunohistochemical method, and tumor necrosis factor-α （TNF-α levels in the culture media were detected by enzymelinked immunosorbent assays （ELISA）. Results In the slices treated with 100 ng/mL LPS for 72 h, the number of TH-IR neurons reduced from 191± 12 in the control slices to 46±4, and the LDH activity elevated obviously （P 〈 0.01）, along with remarkably increased number of OX-42-IR cells and production of TNF-α （P 〈 0.01）. Preconditioning with 3 or 6 ng/mL LPS attenuated neuron loss （the number of TH-IR neurons increased to 126± 12 and 180± 13, respectively） and markedly reduced LDH levels （P 〈 0.05）, accompanied by significant decreases of OX-42-IR microglia activation and TNF-α production （P 〈 0.05）. Conclusion Low-dose LPS preconditioning could protect dopaminergic neurons against inflammatory damage in rat midbrain slice culture, and inhibition of microglial activation and reduction of the proinflammatory factor TNF-α production may contribute to this protective effect. Further understanding the underlying mechanism of LPS preconditioning may open a new window for treatment of Parkinson＇s disease.展开更多
BACKGROUND： Midbrain-derived neural stem cells （mNSCs） can differentiate into functional mature dopaminergic neurons. The mNSCs are considered the ideal choice for cell therapy of Parkinson＇s disease. OBJECTIVE： ...BACKGROUND： Midbrain-derived neural stem cells （mNSCs） can differentiate into functional mature dopaminergic neurons. The mNSCs are considered the ideal choice for cell therapy of Parkinson＇s disease. OBJECTIVE： To isolate rat embryonic mNSCs and to observe the differentiation characteristics of mNSCs induced by cell growth-promoting factors. DESIGN, TIME AND SETTING： An in vitro cell culture study based on the molecular biology of nerve cells was carried out at the Institute of Clinical Medicine, China-Japan Friendship Hospital （China） from March to November 2007. MATERIALS： Sprague Dawley rats at embryonic day 14 were used in this study. Nestin antibody, β-Ⅲ tubulin antibody, glial fibrillary acidic protein （GFAP） antibody and cyclic nucleotide 3＇-phosphohydrolase （CNPase） antibody were provided by Abcam; DMEM/F12 medium and N2 supplement were provided by Invitrogen; epidermal growth factor （EGF） and fibroblast growth factor-2 （FGF2） were provided by R＆D Systems. METHODS： The ventral mesencephalon was dissected from embryonic day 14 rat embryos. By trypsin digestion and mechanical separation, the brain tissue was triturated into a fine single-cell suspension. The cells were cultured in 5 mL serum-free medium containing DMEM/FI 2, 1% N： supplement, 20 ng/mL EGF and FGF2. The mNSCs at the third generation were coated with 10ug/mL polylysine and induced to differentiate in the DMEM/F12 supplemented with 1% fetal bovine serum and 1% N2. MAIN OUTCOME MEASURES： The neural spheres of the third passage were identified by nestin immunofluorescence; at the same time, the cells were induced to differentiate, and the types of differentiated cell were identified by immunofluorescence for β Ⅲ tubulin, GFAP and CNPase. RESULTS： Seven days after primary culture, a great many neurospheres could be obtained by successive pasage. Immunofluorescence assays showed that the neurospheres were nestin positive, and after differentiation, the cells expressed GFAP, CNPase and β -Ⅲ-tubulin. CONCLUSION： Embryonic day 14 rat mNSCs can differentiate into neuron-like cells and glial cells following induction by EGF, FGF2 and N： additive.展开更多
BACKGROUND： Substance P participates in pain transmission and modulation, suggesting a close association with migraine headaches. The clinical application of magnesium has been effective in treating migraines, and th...BACKGROUND： Substance P participates in pain transmission and modulation, suggesting a close association with migraine headaches. The clinical application of magnesium has been effective in treating migraines, and the action mechanisms underlying migraines correlate with substance P expression. OBJECTIVE： To analyze different magnesium doses on behavior and substance P mRNA expression in the midbrain of a rat migraine model, and to determine the action pathway of migraine treatment using magnesium. DESIGN, TIME AND SETTING： A completely randomized, controlled, animal experiment was performed at the Experimental Animal Center and Central Laboratory in the Second Hospital of Jilin University between 2007 and 2008. MATERIALS： Magnesium sulfate （25%） was supplied by Tianjin Pharmaceutical Jiaozuo, China. Nitroglycerin was provided by Shanxi Kangbao Biological, China. Substance P primer sequence was synthesized by TaKaRa Biotechnology （Dalian）, China. METHODS： A total of 36 healthy, adult, Wistar rats were randomly assigned to 6 groups： control, migraine, low- and high-dose magnesium sulfate treated, and low- and high-dose magnesium sulfate control, with 6 rats in each group. Migraines were induced by subcutaneous injection of 10 mg/kg nitroglycerin in the migraine and low- and high-dose magnesium sulfate treated groups, and 2 mL/kg physiological saline was administered to rats in the control and low- and high-dose of magnesium sulfate control groups. Five minutes following administration, rats in low-dose groups were intraperitoneally injected with 100 mg/kg magnesium sulfate, while those in high-dose groups were injected with 300 mg/kg magnesium sulfate. No interventions were administered to the control and migraine groups. MAIN OUTCOME MEASURES： At 2 hours after nitroglycerin injection, substance P mRNA expression in the rat midbrain was measured by real-time quantitative polymerase chain reaction. At 60-90 minutes after nitroglycerin injection, behavioral changes of pain were analyzed in the experimental rats. RESULTS： The migraine group exhibited significantly lower levels of substance P mRNA expression compared with the control group （P 〈 0.05）. Following magnesium sulfate injection, substance P mRNA expression increased, compared with the migraine and control groups （P 〈 0.05）. In the low- and high-dose magnesium sulfate treated groups, pain behavior was remarkably ameliorated, compared with the migraine group （P 〈 0.05）, particularly with the high-dose injection （P 〈 0.05）. CONCLUSION： Magnesium relieved pain behaviors in a rat migraine model in a dose-dependent manner, and the therapeutic effect was achieved in conjunction with increased substance P expression in the midbrain.展开更多
Biological robot is a kind of creature controlled by human beings by applying intervention signals through control technology to regulate biological behavior.At present,the research on bio-robot mainly focuses on terr...Biological robot is a kind of creature controlled by human beings by applying intervention signals through control technology to regulate biological behavior.At present,the research on bio-robot mainly focuses on terrestrial mammals and insects,while the research on aquatic animal robot is less.Early studies have shown that the medial longitudinal fasciculus nucleus(NFLM)of carp midbrain was related to tail wagging,but the research has not been applied to the navigation control of the carp robot.The purpose of this study is to realize the quantitative control of the forward and steering behavior of the carp robot by NFLM electrical stimulation.Under the condition of no craniotomy,brain electrode was implanted into the NFLM of the carp midbrain,and the underwater control experiment was carried out by applying different electrical stimulation parameters.Using the ImageJ software and self-programmed,the forward motion speed and steering angle of steering motion of the carp robot before and after being stimulated were calculated.The experimental results showed for the carp robot that was induced the steering motion,the left and right steering motion of 30°to 150°could be achieved by adjusting the stimulation parameters,for the carp robot that was induced the forward motion,the speed of forward motion could be controlled to reach 100 cm/s.The research lays a foundation for the accurate control of the forward and steering motion of the aquatic animal robot.展开更多
BACKGROUND Wernekink commissural syndrome(WCS)is a distinct midbrain syndrome that involves the caudal tegmentum of the midbrain and selectively damages the Wernekink commissure involved in the decussation of the supe...BACKGROUND Wernekink commissural syndrome(WCS)is a distinct midbrain syndrome that involves the caudal tegmentum of the midbrain and selectively damages the Wernekink commissure involved in the decussation of the superior cerebellar peduncle in midbrain.The aim of the study was to explore the clinical manifestations,imaging characteristics,and differential diagnosis of WCS in midbrain infarction to provide reference for clinicians in the diagnosis of WCS.CASE SUMMARY The clinical data of 4 patients with WCS with midbrain infarction were analyzed retrospectively.WCS is a rare syndrome that can be diagnosed based on its characteristic symptoms and imaging findings of magnetic resonance imaging.CONCLUSION Clinicians should look for this syndrome in cases of bilateral cerebellar dysfunction and eye movement disorders.展开更多
Parkinson＇s disease（PD）is the second most common neurodegenerative disease after Alzheimer＇s disease.The etiology of PD is still not completely understood,but the degeneration of dopaminergic（DA）neurons in the s...Parkinson＇s disease（PD）is the second most common neurodegenerative disease after Alzheimer＇s disease.The etiology of PD is still not completely understood,but the degeneration of dopaminergic（DA）neurons in the substantia nigra pars compacta（SNpc）,loss of DA innervation of the striatum,and protein aggregates in the form of Lewy bodies and neurites are its established hallmarks. In addition to α-synuclein accumu- lation in Lewy bodies and neurites, genetic mutations in the genes encoding parkin, PINK, DJ-1, LRRK2 and other proteins are associated with the inherited form of PD. An association study linked also the receptor tyrosine kinase Ret to PD （Meka et al., 2015）. Currently there are only symptomatic treatments available for PD but no cure. Consequently much effort is being made to find neurotrophic and other factors able to stimulate SNpc DA neuron protection and regeneration.展开更多
This study showed that abnormal behavioral changes were greatly improved in rats displaying Parkinson＇s disease-like symptoms after intragastric administration of Xifeng Dingchan decoction at 15, 7.5, 3.75 g/kg per d...This study showed that abnormal behavioral changes were greatly improved in rats displaying Parkinson＇s disease-like symptoms after intragastric administration of Xifeng Dingchan decoction at 15, 7.5, 3.75 g/kg per day. In addition, tyrosine hydroxylase mRNA expression in the substantia nigra of the midbrain was up-regulated, and tyrosine hydroxylase content in the midbrain ventral tegmentum and substantia nigra pars compacta was also increased. The effect of administration of Xifeng Dingchan decoction at 7.5 g/kg per day was similar to that of Madopar at 67.5 mg/kg per day. These results indicate that the therapeutic effect of Xifeng Dingchan decoction on Parkinson＇s disease is associated with the up-regulated protein and mRNA expression of tyrosine hydroxylase in the midbrain.展开更多
Dorsal midbrain syndrome or Parinaud syndrome is a supranuclear brainstem syndrome involving the vertical gaze centre.These are case series with three patients who were diagnosed with dorsal midbrain syndrome secondar...Dorsal midbrain syndrome or Parinaud syndrome is a supranuclear brainstem syndrome involving the vertical gaze centre.These are case series with three patients who were diagnosed with dorsal midbrain syndrome secondary to pineal gland tumours.The prognosis varied depending on tumour types,age of presentation and treatment received.All of them were presented with life-threatening obstructive hydrocephalus.Our first patient was successfully treated with emergency surgery followed by radiotherapy.He regained normal visual acuity and full recovery of his ocular movement.Second and third patients had undergone surgery for raised intracranial pressure.Both had an inoperable pineal gland tumour.As for our second patient,we detected a worsening of vertical gaze during his four years follow-up.However,his bilateral good visual acuity was preserved.The third patient passed away as a result of uncontrolled enlarging tumour.We also briefly reviewed the clinical presentation,diagnosis,and therapeutic approach of the three patients.One of the caveats is that urgent radiological study is crucial to differentiate the tumour type via the pathognomonic features and to delineate the tumour extension.The preferable treatment options vary among each tumour type.A multidisciplinary approach is crucial in early detection,in addition to treatment initiation and long term follow up to achieve a better outcome.展开更多
Introduction： Parkinson＇s disease （PD） is a chronic, age-re- lated neurodegenerative disorder that affects 1-2% of the population over the age of 65. PD is characterised by the progressive degeneration of nigrostr...Introduction： Parkinson＇s disease （PD） is a chronic, age-re- lated neurodegenerative disorder that affects 1-2% of the population over the age of 65. PD is characterised by the progressive degeneration of nigrostriatal dopaminergic （DA） neurons. This leads to disabling motor symptoms, due to the striatal DA denervation. Despite decades of research, there is still no therapy that can slow, stop or regenerate the dying midbrain DA neurons in PD.展开更多
Dopamine cell bodies in the substantia nigra of the midbrain and with their terminals projecting to the neostriatum form the nigrostriatum and these dopamine neurons degenerate in Parkinson’s disease (PD). Based on m...Dopamine cell bodies in the substantia nigra of the midbrain and with their terminals projecting to the neostriatum form the nigrostriatum and these dopamine neurons degenerate in Parkinson’s disease (PD). Based on metabolic and func- tional specialization of the cell bodies versus the axon terminals, the level and disposition of dopamine, its metabolites and enzymes are different in both regions and are likely to be affected differently in PD. We examined changes in the midbrain dopamine system following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to test the hypothesis that a predisposing/sensitization stage and a inducing/precipitating stage underlie PD. Pregnant mice were treated with a low dose of MPTP during gestation days 8 - 12 to model the predisposing/sensitization stage, by interrupting the fetal mid- brain dopamine system during its neurogenesis. For the inducing/precipitating stage, the 12-weeks offspring were ad- ministered MPTP. The prenatal-MPTP offspring appear normal, but midbrain dopamine, 3,4-di-hydroxy-phenyl-acetic- acid, 3-methoxytyramine, tyrosine-hydroxylase and L-aromatic-amino-acid-decarboxylase, were reduced by 49.6%, 48%, 54%, 20.9% and 25%. Postnatal-MPTP of 10, 20, 30 mg/kg administered to the prenatal-PBS vs prenatal-MPTP offspring reduced midbrain dopamine by 43.6%, 47.2%, 70.3% vs 85.4%, 89.1%, 95.2%;tyrosine-hydroxylase by 30%, 63%, 81% vs 30.7%, 70.4%, 91.4%;L-aromatic-amino-acid-decarboxylase by 0%, 2%, 40% vs 32%, 40%, 58%. The prenatal-MPTP may render the DA system sensitive by causing sub-threshold reduction of DA, its metabolites and en- zymes, enabling postnatal-MPTP to reduce dopamine above the 70% - 80% PD-inducing threshold. Thus, the study may produce a prenatal predisposing/sensitization and postnatal inducing/precipitation model of PD. It also indicates that some cases of PD may have a fetal basis, in which sub-threshold nigrostriatal impairments occur early in life and PD-symptoms are induced during aging by further insults to the dopaminergic system that would not cause PD symptoms in normal indi-viduals.展开更多
Midbrain stroke is uncommon. We are presenting an interesting case of a patient with rare isolated left midbrain stroke. The patient had third cranial nerve palsy. Magnetic resonance imaging (MRI) brain showed acute s...Midbrain stroke is uncommon. We are presenting an interesting case of a patient with rare isolated left midbrain stroke. The patient had third cranial nerve palsy. Magnetic resonance imaging (MRI) brain showed acute stroke at the medial part of left midbrain. Magnetic resonance angiography (MRA) was normal.展开更多
Parkinson’s disease（PD）is characterized by the progressive loss of midbrain dopaminergic（m DA）neurons and a subsequent decrease in striatal dopamine levels,which cause the typical clinical motor symptoms such as ...Parkinson’s disease（PD）is characterized by the progressive loss of midbrain dopaminergic（m DA）neurons and a subsequent decrease in striatal dopamine levels,which cause the typical clinical motor symptoms such as muscle rigidity,bradykinesia and tremor.展开更多
Objective:to describe the clinical fea-tures of Holmes tremor(HT)in the head and neck region caused by midbrain and thalamus hemorrhage.Methods:we collected the clinical history and examination data of a patient with ...Objective:to describe the clinical fea-tures of Holmes tremor(HT)in the head and neck region caused by midbrain and thalamus hemorrhage.Methods:we collected the clinical history and examination data of a patient with HT in the head and neck region.Results:the patient had HT in the head and neck region with dizzi-ness.Brain computed to mography(CT)showed midbrain and thalamus hemorrhage.Conclusion:HT in the head and neck region as a delayed complication of midbrain and thalamus stroke are rare in clinic.When patients have a tremor in the head and neck region after midbrain or thalamus stroke,HT should be considered.展开更多
Hypertrophic olivary degeneration(HOD)arises from lesions of the dentato-rubro-olivary pathway(GuillaineMollaret triangle),and bilateral HOD is the rarest.Our patient,a 42-year-old man with bilateral HOD caused by uni...Hypertrophic olivary degeneration(HOD)arises from lesions of the dentato-rubro-olivary pathway(GuillaineMollaret triangle),and bilateral HOD is the rarest.Our patient,a 42-year-old man with bilateral HOD caused by unilateral midbrain infarction,had both increased dizziness and ataxia as the first symptoms.HOD has no effective treatment and is easily misdiagnosed as other diseases in clinical practice.Our case demonstrated unique HOD symptomatology and emphasizes the important role of magnetic resonance imaging in diagnosing HOD.The use of gabapentin relieved nystagmus in our patient and may provide a reference for the future treatment of such patients.展开更多
Neurons synthesizing the neurotransmitter dopamine exert crucial functions in the mammalian brain. The biggest and most important population of dopamine-synthesizing neurons is located in the mammalian ventral midbra...Neurons synthesizing the neurotransmitter dopamine exert crucial functions in the mammalian brain. The biggest and most important population of dopamine-synthesizing neurons is located in the mammalian ventral midbrain （VM）, and controls and modulates the exe- cution of motor, cognitive, affective, motivational, and rewarding behaviours. Degeneration of these neurons leads to motor deficits that are characteristic of Parkinson＇s disease, while their dysfunction is involved in the pathogenesis of psychiatric disorders including schizophrenia and addiction. Because the aetiology and therapeutic prospects for these diseases include neurodevelopmental aspects, substantial scientific interest has been focused on deciphering the mechanistic pathways that control the generation and sur- vival of these neurons during embryonic development. Researches during the last decade revealed the pivotal role of the secreted Wntl ligand and its signaUing cascade in the generation of the dopamine-synthesizing neurons in the mammalian VM. Here, we summarize the initial and more recent findings that have unravelled several Wntl-controUed genetic networks required for the proliferation and commitment of VM progenitors to the dopaminergic cell fate during midgestational embryonic stages, and for the correct differentiation of these progenitors into postmitotic dopamine-synthesizing neurons at late midgestational embryonic and foetal stages.展开更多
Holmes＇ tremor has been postulated as a syndrome .attributed to those lesions that interrupt the dentatethalamic and the nigrostriatal tracts thus causing both an action and a rest tremor. It may arise from various u...Holmes＇ tremor has been postulated as a syndrome .attributed to those lesions that interrupt the dentatethalamic and the nigrostriatal tracts thus causing both an action and a rest tremor. It may arise from various underlying structural disorders including multiple sclerosis, stroke, or tumors. So far, to our knowledge, few studies on Holmes＇ tremor secondary to cavemoma have been reported. Here we report a case of disabling tremor, who harbored a cavemoma in the midbrain.展开更多
基金supported by the National Natural Science Foundation of China,No.81771222(to LS)Guangzhou Key Research Program on Brain Science,Nos.202007030011,202206060001(to LS)the Program of Introducing Talents of Discipline to Universities of China,No.B14036(to KFS)。
文摘Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases.They also represent a potential source of transplanted cells for therapeutic applications.In vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal development.Emerging evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons feasible.Using SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic neurons.To obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of induction.This increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing neurons.We further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 staining.Thus,we have established three induction protocols for dopaminergic neurons.Based on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.
基金the Foundation of Beijing Municipal Commission of Education,China (No.200410025011)
文摘Objective To identify the protective effect of lipopolysaccharide （LPS） preconditioning against LPS-induced inflammatory damage in dopaminergic neurons of midbrain slice culture and the possible mechanisms. Methods After cultured in vitro for 14 d, the rat organotypic midbrain slices were pretreated with different concentrations （0, 1, 3, 6 or 10 ng/mL） of LPS for 24 h followed by treatment with 100 ng/mL LPS for 72 h. The whole slice viability was detelmined by measurement of the activity of lactic acid dehydrogenase （LDH）. Tyrosine hydroxylase-immunoreactive （TH-IR） neurons and CD 1 1 b/c equivalent-immunoreactive （OX-42-IR） microglia in the slices were observed by immunohistochemical method, and tumor necrosis factor-α （TNF-α levels in the culture media were detected by enzymelinked immunosorbent assays （ELISA）. Results In the slices treated with 100 ng/mL LPS for 72 h, the number of TH-IR neurons reduced from 191± 12 in the control slices to 46±4, and the LDH activity elevated obviously （P 〈 0.01）, along with remarkably increased number of OX-42-IR cells and production of TNF-α （P 〈 0.01）. Preconditioning with 3 or 6 ng/mL LPS attenuated neuron loss （the number of TH-IR neurons increased to 126± 12 and 180± 13, respectively） and markedly reduced LDH levels （P 〈 0.05）, accompanied by significant decreases of OX-42-IR microglia activation and TNF-α production （P 〈 0.05）. Conclusion Low-dose LPS preconditioning could protect dopaminergic neurons against inflammatory damage in rat midbrain slice culture, and inhibition of microglial activation and reduction of the proinflammatory factor TNF-α production may contribute to this protective effect. Further understanding the underlying mechanism of LPS preconditioning may open a new window for treatment of Parkinson＇s disease.
基金the National Natural Science Foundation of China,No.30672151
文摘BACKGROUND： Midbrain-derived neural stem cells （mNSCs） can differentiate into functional mature dopaminergic neurons. The mNSCs are considered the ideal choice for cell therapy of Parkinson＇s disease. OBJECTIVE： To isolate rat embryonic mNSCs and to observe the differentiation characteristics of mNSCs induced by cell growth-promoting factors. DESIGN, TIME AND SETTING： An in vitro cell culture study based on the molecular biology of nerve cells was carried out at the Institute of Clinical Medicine, China-Japan Friendship Hospital （China） from March to November 2007. MATERIALS： Sprague Dawley rats at embryonic day 14 were used in this study. Nestin antibody, β-Ⅲ tubulin antibody, glial fibrillary acidic protein （GFAP） antibody and cyclic nucleotide 3＇-phosphohydrolase （CNPase） antibody were provided by Abcam; DMEM/F12 medium and N2 supplement were provided by Invitrogen; epidermal growth factor （EGF） and fibroblast growth factor-2 （FGF2） were provided by R＆D Systems. METHODS： The ventral mesencephalon was dissected from embryonic day 14 rat embryos. By trypsin digestion and mechanical separation, the brain tissue was triturated into a fine single-cell suspension. The cells were cultured in 5 mL serum-free medium containing DMEM/FI 2, 1% N： supplement, 20 ng/mL EGF and FGF2. The mNSCs at the third generation were coated with 10ug/mL polylysine and induced to differentiate in the DMEM/F12 supplemented with 1% fetal bovine serum and 1% N2. MAIN OUTCOME MEASURES： The neural spheres of the third passage were identified by nestin immunofluorescence; at the same time, the cells were induced to differentiate, and the types of differentiated cell were identified by immunofluorescence for β Ⅲ tubulin, GFAP and CNPase. RESULTS： Seven days after primary culture, a great many neurospheres could be obtained by successive pasage. Immunofluorescence assays showed that the neurospheres were nestin positive, and after differentiation, the cells expressed GFAP, CNPase and β -Ⅲ-tubulin. CONCLUSION： Embryonic day 14 rat mNSCs can differentiate into neuron-like cells and glial cells following induction by EGF, FGF2 and N： additive.
基金a grant by Jilin Provincial Science and Technology Bureau,No. 200705238
文摘BACKGROUND： Substance P participates in pain transmission and modulation, suggesting a close association with migraine headaches. The clinical application of magnesium has been effective in treating migraines, and the action mechanisms underlying migraines correlate with substance P expression. OBJECTIVE： To analyze different magnesium doses on behavior and substance P mRNA expression in the midbrain of a rat migraine model, and to determine the action pathway of migraine treatment using magnesium. DESIGN, TIME AND SETTING： A completely randomized, controlled, animal experiment was performed at the Experimental Animal Center and Central Laboratory in the Second Hospital of Jilin University between 2007 and 2008. MATERIALS： Magnesium sulfate （25%） was supplied by Tianjin Pharmaceutical Jiaozuo, China. Nitroglycerin was provided by Shanxi Kangbao Biological, China. Substance P primer sequence was synthesized by TaKaRa Biotechnology （Dalian）, China. METHODS： A total of 36 healthy, adult, Wistar rats were randomly assigned to 6 groups： control, migraine, low- and high-dose magnesium sulfate treated, and low- and high-dose magnesium sulfate control, with 6 rats in each group. Migraines were induced by subcutaneous injection of 10 mg/kg nitroglycerin in the migraine and low- and high-dose magnesium sulfate treated groups, and 2 mL/kg physiological saline was administered to rats in the control and low- and high-dose of magnesium sulfate control groups. Five minutes following administration, rats in low-dose groups were intraperitoneally injected with 100 mg/kg magnesium sulfate, while those in high-dose groups were injected with 300 mg/kg magnesium sulfate. No interventions were administered to the control and migraine groups. MAIN OUTCOME MEASURES： At 2 hours after nitroglycerin injection, substance P mRNA expression in the rat midbrain was measured by real-time quantitative polymerase chain reaction. At 60-90 minutes after nitroglycerin injection, behavioral changes of pain were analyzed in the experimental rats. RESULTS： The migraine group exhibited significantly lower levels of substance P mRNA expression compared with the control group （P 〈 0.05）. Following magnesium sulfate injection, substance P mRNA expression increased, compared with the migraine and control groups （P 〈 0.05）. In the low- and high-dose magnesium sulfate treated groups, pain behavior was remarkably ameliorated, compared with the migraine group （P 〈 0.05）, particularly with the high-dose injection （P 〈 0.05）. CONCLUSION： Magnesium relieved pain behaviors in a rat migraine model in a dose-dependent manner, and the therapeutic effect was achieved in conjunction with increased substance P expression in the midbrain.
基金This work was financially supported by the Project of National Natural Science Foundation of China(project number:61573305)Projectof Natural Science Foundation of Hebei Provinceof China(project number:F2019203511)National High-Tech Research and Development Plan of China(863 Plan)Project(2013AA***)Fund.
文摘Biological robot is a kind of creature controlled by human beings by applying intervention signals through control technology to regulate biological behavior.At present,the research on bio-robot mainly focuses on terrestrial mammals and insects,while the research on aquatic animal robot is less.Early studies have shown that the medial longitudinal fasciculus nucleus(NFLM)of carp midbrain was related to tail wagging,but the research has not been applied to the navigation control of the carp robot.The purpose of this study is to realize the quantitative control of the forward and steering behavior of the carp robot by NFLM electrical stimulation.Under the condition of no craniotomy,brain electrode was implanted into the NFLM of the carp midbrain,and the underwater control experiment was carried out by applying different electrical stimulation parameters.Using the ImageJ software and self-programmed,the forward motion speed and steering angle of steering motion of the carp robot before and after being stimulated were calculated.The experimental results showed for the carp robot that was induced the steering motion,the left and right steering motion of 30°to 150°could be achieved by adjusting the stimulation parameters,for the carp robot that was induced the forward motion,the speed of forward motion could be controlled to reach 100 cm/s.The research lays a foundation for the accurate control of the forward and steering motion of the aquatic animal robot.
文摘BACKGROUND Wernekink commissural syndrome(WCS)is a distinct midbrain syndrome that involves the caudal tegmentum of the midbrain and selectively damages the Wernekink commissure involved in the decussation of the superior cerebellar peduncle in midbrain.The aim of the study was to explore the clinical manifestations,imaging characteristics,and differential diagnosis of WCS in midbrain infarction to provide reference for clinicians in the diagnosis of WCS.CASE SUMMARY The clinical data of 4 patients with WCS with midbrain infarction were analyzed retrospectively.WCS is a rare syndrome that can be diagnosed based on its characteristic symptoms and imaging findings of magnetic resonance imaging.CONCLUSION Clinicians should look for this syndrome in cases of bilateral cerebellar dysfunction and eye movement disorders.
基金supported by grants from the DFG (KR 3529/4-1 to ERK)the town of Hamburg (Lexi to ERK)
文摘Parkinson＇s disease（PD）is the second most common neurodegenerative disease after Alzheimer＇s disease.The etiology of PD is still not completely understood,but the degeneration of dopaminergic（DA）neurons in the substantia nigra pars compacta（SNpc）,loss of DA innervation of the striatum,and protein aggregates in the form of Lewy bodies and neurites are its established hallmarks. In addition to α-synuclein accumu- lation in Lewy bodies and neurites, genetic mutations in the genes encoding parkin, PINK, DJ-1, LRRK2 and other proteins are associated with the inherited form of PD. An association study linked also the receptor tyrosine kinase Ret to PD （Meka et al., 2015）. Currently there are only symptomatic treatments available for PD but no cure. Consequently much effort is being made to find neurotrophic and other factors able to stimulate SNpc DA neuron protection and regeneration.
基金Projects of Heilongjiang Province Administration of Traditional Chinese Medicine,No.ZH04Z74Second-Class Award of Scientific Advancement of Heilongjiang Province Administration of Traditional Chinese Medicine in 2007
文摘This study showed that abnormal behavioral changes were greatly improved in rats displaying Parkinson＇s disease-like symptoms after intragastric administration of Xifeng Dingchan decoction at 15, 7.5, 3.75 g/kg per day. In addition, tyrosine hydroxylase mRNA expression in the substantia nigra of the midbrain was up-regulated, and tyrosine hydroxylase content in the midbrain ventral tegmentum and substantia nigra pars compacta was also increased. The effect of administration of Xifeng Dingchan decoction at 7.5 g/kg per day was similar to that of Madopar at 67.5 mg/kg per day. These results indicate that the therapeutic effect of Xifeng Dingchan decoction on Parkinson＇s disease is associated with the up-regulated protein and mRNA expression of tyrosine hydroxylase in the midbrain.
文摘Dorsal midbrain syndrome or Parinaud syndrome is a supranuclear brainstem syndrome involving the vertical gaze centre.These are case series with three patients who were diagnosed with dorsal midbrain syndrome secondary to pineal gland tumours.The prognosis varied depending on tumour types,age of presentation and treatment received.All of them were presented with life-threatening obstructive hydrocephalus.Our first patient was successfully treated with emergency surgery followed by radiotherapy.He regained normal visual acuity and full recovery of his ocular movement.Second and third patients had undergone surgery for raised intracranial pressure.Both had an inoperable pineal gland tumour.As for our second patient,we detected a worsening of vertical gaze during his four years follow-up.However,his bilateral good visual acuity was preserved.The third patient passed away as a result of uncontrolled enlarging tumour.We also briefly reviewed the clinical presentation,diagnosis,and therapeutic approach of the three patients.One of the caveats is that urgent radiological study is crucial to differentiate the tumour type via the pathognomonic features and to delineate the tumour extension.The preferable treatment options vary among each tumour type.A multidisciplinary approach is crucial in early detection,in addition to treatment initiation and long term follow up to achieve a better outcome.
基金supported by grants from the Irish Research Council(R15897SVH/AMS/GWO’K)+4 种基金the National University of Ireland(R16189SVH/AMS/GWO’K)Royal Irish Academy(SVH/AMS/GWO’K)Science Foundation Ireland(15/CDA/3498GWO’K)
文摘Introduction： Parkinson＇s disease （PD） is a chronic, age-re- lated neurodegenerative disorder that affects 1-2% of the population over the age of 65. PD is characterised by the progressive degeneration of nigrostriatal dopaminergic （DA） neurons. This leads to disabling motor symptoms, due to the striatal DA denervation. Despite decades of research, there is still no therapy that can slow, stop or regenerate the dying midbrain DA neurons in PD.
文摘Dopamine cell bodies in the substantia nigra of the midbrain and with their terminals projecting to the neostriatum form the nigrostriatum and these dopamine neurons degenerate in Parkinson’s disease (PD). Based on metabolic and func- tional specialization of the cell bodies versus the axon terminals, the level and disposition of dopamine, its metabolites and enzymes are different in both regions and are likely to be affected differently in PD. We examined changes in the midbrain dopamine system following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to test the hypothesis that a predisposing/sensitization stage and a inducing/precipitating stage underlie PD. Pregnant mice were treated with a low dose of MPTP during gestation days 8 - 12 to model the predisposing/sensitization stage, by interrupting the fetal mid- brain dopamine system during its neurogenesis. For the inducing/precipitating stage, the 12-weeks offspring were ad- ministered MPTP. The prenatal-MPTP offspring appear normal, but midbrain dopamine, 3,4-di-hydroxy-phenyl-acetic- acid, 3-methoxytyramine, tyrosine-hydroxylase and L-aromatic-amino-acid-decarboxylase, were reduced by 49.6%, 48%, 54%, 20.9% and 25%. Postnatal-MPTP of 10, 20, 30 mg/kg administered to the prenatal-PBS vs prenatal-MPTP offspring reduced midbrain dopamine by 43.6%, 47.2%, 70.3% vs 85.4%, 89.1%, 95.2%;tyrosine-hydroxylase by 30%, 63%, 81% vs 30.7%, 70.4%, 91.4%;L-aromatic-amino-acid-decarboxylase by 0%, 2%, 40% vs 32%, 40%, 58%. The prenatal-MPTP may render the DA system sensitive by causing sub-threshold reduction of DA, its metabolites and en- zymes, enabling postnatal-MPTP to reduce dopamine above the 70% - 80% PD-inducing threshold. Thus, the study may produce a prenatal predisposing/sensitization and postnatal inducing/precipitation model of PD. It also indicates that some cases of PD may have a fetal basis, in which sub-threshold nigrostriatal impairments occur early in life and PD-symptoms are induced during aging by further insults to the dopaminergic system that would not cause PD symptoms in normal indi-viduals.
文摘Midbrain stroke is uncommon. We are presenting an interesting case of a patient with rare isolated left midbrain stroke. The patient had third cranial nerve palsy. Magnetic resonance imaging (MRI) brain showed acute stroke at the medial part of left midbrain. Magnetic resonance angiography (MRA) was normal.
文摘Parkinson’s disease（PD）is characterized by the progressive loss of midbrain dopaminergic（m DA）neurons and a subsequent decrease in striatal dopamine levels,which cause the typical clinical motor symptoms such as muscle rigidity,bradykinesia and tremor.
文摘Objective:to describe the clinical fea-tures of Holmes tremor(HT)in the head and neck region caused by midbrain and thalamus hemorrhage.Methods:we collected the clinical history and examination data of a patient with HT in the head and neck region.Results:the patient had HT in the head and neck region with dizzi-ness.Brain computed to mography(CT)showed midbrain and thalamus hemorrhage.Conclusion:HT in the head and neck region as a delayed complication of midbrain and thalamus stroke are rare in clinic.When patients have a tremor in the head and neck region after midbrain or thalamus stroke,HT should be considered.
基金supported by a 2019 Joint Construction Project of the Henan Provincial Health Committee and Ministry of Health(Grant no.SB201901061)the Henan Key Laboratory of Neurorestoratology(Grant no.HNSJXF-2021-004).
文摘Hypertrophic olivary degeneration(HOD)arises from lesions of the dentato-rubro-olivary pathway(GuillaineMollaret triangle),and bilateral HOD is the rarest.Our patient,a 42-year-old man with bilateral HOD caused by unilateral midbrain infarction,had both increased dizziness and ataxia as the first symptoms.HOD has no effective treatment and is easily misdiagnosed as other diseases in clinical practice.Our case demonstrated unique HOD symptomatology and emphasizes the important role of magnetic resonance imaging in diagnosing HOD.The use of gabapentin relieved nystagmus in our patient and may provide a reference for the future treatment of such patients.
文摘Neurons synthesizing the neurotransmitter dopamine exert crucial functions in the mammalian brain. The biggest and most important population of dopamine-synthesizing neurons is located in the mammalian ventral midbrain （VM）, and controls and modulates the exe- cution of motor, cognitive, affective, motivational, and rewarding behaviours. Degeneration of these neurons leads to motor deficits that are characteristic of Parkinson＇s disease, while their dysfunction is involved in the pathogenesis of psychiatric disorders including schizophrenia and addiction. Because the aetiology and therapeutic prospects for these diseases include neurodevelopmental aspects, substantial scientific interest has been focused on deciphering the mechanistic pathways that control the generation and sur- vival of these neurons during embryonic development. Researches during the last decade revealed the pivotal role of the secreted Wntl ligand and its signaUing cascade in the generation of the dopamine-synthesizing neurons in the mammalian VM. Here, we summarize the initial and more recent findings that have unravelled several Wntl-controUed genetic networks required for the proliferation and commitment of VM progenitors to the dopaminergic cell fate during midgestational embryonic stages, and for the correct differentiation of these progenitors into postmitotic dopamine-synthesizing neurons at late midgestational embryonic and foetal stages.
文摘Holmes＇ tremor has been postulated as a syndrome .attributed to those lesions that interrupt the dentatethalamic and the nigrostriatal tracts thus causing both an action and a rest tremor. It may arise from various underlying structural disorders including multiple sclerosis, stroke, or tumors. So far, to our knowledge, few studies on Holmes＇ tremor secondary to cavemoma have been reported. Here we report a case of disabling tremor, who harbored a cavemoma in the midbrain.
