Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is r...Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.展开更多
Picornaviridae are a family of small positive-strand RNA viruses,and transmitted via the respiratory or fecal-oral route.The neurotropic picornaviruses can induce acute or late recurrent seizures following central ner...Picornaviridae are a family of small positive-strand RNA viruses,and transmitted via the respiratory or fecal-oral route.The neurotropic picornaviruses can induce acute or late recurrent seizures following central nervous system infection,by infecting the peripheral nerve,crossing the blood-brain barrier and migrating in the Trojan-horse method.Theiler’s murine encephalomyelitis virus(TMEV),as a member of Picornaviridae family,can cause encephalitis,leading to chronic spontaneous seizures.TMEV-infected C57BL/6 mice have been used as an animal model for exploring the mechanism of epileptogenesis and assessing new antiepileptic drugs.Astrogliosis,neuronal death and microglial recruitment have been detected in the hippocampus following the picornaviruse-induced encephalitis.The macrophages,monocytes,neutrophils,as well as IL-6 and TNF-αreleased by them,play an important role in the epileptogenesis.In this review,we summarize the clinical characteristics of picornavirus infection,and the immunopathology involved in the TMEV-induced epilepsy.展开更多
文摘Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.
基金supported by the National Natural Science Foundation of Shandong,China(ZR2019PH040)the National Natural Science Foundation of China(81901321).
文摘Picornaviridae are a family of small positive-strand RNA viruses,and transmitted via the respiratory or fecal-oral route.The neurotropic picornaviruses can induce acute or late recurrent seizures following central nervous system infection,by infecting the peripheral nerve,crossing the blood-brain barrier and migrating in the Trojan-horse method.Theiler’s murine encephalomyelitis virus(TMEV),as a member of Picornaviridae family,can cause encephalitis,leading to chronic spontaneous seizures.TMEV-infected C57BL/6 mice have been used as an animal model for exploring the mechanism of epileptogenesis and assessing new antiepileptic drugs.Astrogliosis,neuronal death and microglial recruitment have been detected in the hippocampus following the picornaviruse-induced encephalitis.The macrophages,monocytes,neutrophils,as well as IL-6 and TNF-αreleased by them,play an important role in the epileptogenesis.In this review,we summarize the clinical characteristics of picornavirus infection,and the immunopathology involved in the TMEV-induced epilepsy.
