Establishment Of A Model Of Immune-mediated Motoneuron Injury And Its Pathogenesis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons in the cortex, brainstem, and spinal cord. The clinical manifestations of ALS include chronic, progressive weakness and muscle atrophy, together with signs of corticospinal tracts. Most of ALS patients died of respiratory failure within 3~5 years after the onset of symptoms. ALS occurs in both sporadic (sALS) and familial (fALS) forms, which are clinically and pathologically similar. FALS accounts for 5%~10% of diagnosed cases, with sALS comprising the remainder of diagnoses. Approximately 20% of fALS cases are associated with mutations in the gene for copper/zinc superoxide dismutase, SOD1. Although the pathogenesis of sALS remains unknown, many theories have been proposed to account for the selective degeneration of motoneurons in ALS, including1) the involvement of autoimmune mechanisms, 2) oxidative stress, 3) excitotoxicity caused by elevated extracelluar glutamate concentration, 4) excessive phosphorylation of neurofilaments 5) mitochondria dysfunction, and so on.At present, significant evidence has suggested that autoimmune mechanism may involve in the process of motoneuron injury in ALS.T-cell infiltrates were found in the spinal cord in ALS autopsy cases.Antibodies to calcium channel were observed in ALS serum. When ALS IgG was passively transfered to mice, it can cause paralysis of himd limbs and IgG localization in motor neurons and motor axon terminals. All of the above support that autoimmune may involve in the pathophysiological process of SALS. Therefore, the establishment of stable immune-mediated animal model of motor neuron injury is very helpful for study of ALS pathogenesis and motoneuron protection.We established animal model of immune-mediated motor neuron injury by immunizing guinea pigs with bovine spinal cord ventral horn...