Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining.
Epilepsy is a serious neurological disorder in human beings and the long-term pathological events remain largely obscure. We are interested in elucidating long-term brain injury that may occur in the temporal lobe epilepsy, and time-course of neuronal death was examined in a mouse pilocarpine model of chronic epilepsy by Fluoro-Jade C (FJC) dye that can specifically stain the degenerative neurons in the central nervous system. The FJC stain combined with immunohistochemistry to neuronal nuclear specific protein revealed that pilocarpine-induced status epilepticus (SE) resulted in massive degenerative death of neuronal cells in brains with their dense distribution in the cerebral cortex and hippocampus. The FJC-positive degenerating neurons, most of them also expressed apoptosis signaling molecules such as caspase-9 and activated caspase-3, occurred at 4h, increased into peak levels at 12h-3d, and then gradually went down at 7d-14d after onset of SE. More interestingly, a large percentage (about 88%) of FJC-positive degenerative neurons were GABAergic as indicated with their immunoreactivity to glutamic acid decarboxylase-67, implying that inhibitory function of GABAergic neural system might by seriously damaged in brains subject to SE attack in this mouse pilocarpine model. Taken together with previous studies, time-course of degenerative neurons in the mouse pilocarpine model by Fluoro-Jade C staining further benefits understanding of long-term brain pathological changes and recurrent seizure mechanism, and may also result in finding the most suitable time-window in therapeutic manipulation of the chronic epilepsy in human beings.
Wang
Lian
L
Institute of Neurosciences, The Fourth Military Medical University, Xi'an 710032, PR China.
Liu
Yong-Hong
YH
Huang
Yuan-Gui
YG
Chen
Liang-Wei
LW
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D002908:Chronic Disease; D003292:Convulsants; D004195:Disease Models, Animal; D004827:Epilepsy / Q000473:pathology* / Q000503:physiopathology; D005452:Fluoresceins / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000473:pathology* / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000473:pathology*; D009930:Organic Chemicals / Q000737:chemistry; D010862:Pilocarpine; D013194:Staining and Labeling; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D003292:Convulsants; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; C435731:fluoro jade; C534582:fluoro-jade C; D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1