Striatal vulnerability and functional repair by neural grafts

Systemic administration of 3-nitropropionic acid (3-NPA, 20 mg/kg, s.c., daily，2或3 days) to rats induced striatum selective lesions，and animals manifested motor symptoms. In the present study，我们analyzed the mechanisms of the striatal vulnerability and tried to protect the damage.Results are如follows. 1.3 -NPA intoxication induces the depletion of ATP thus leading to the depolarization ofcell membrane and release of glutamate. the depolarization and the excess amount of glutamateinduce neuronal cell death in the center of the striatum.2. the depolarization also induces theexcess release of dopamine (DA) that leads to neuronal and astroglial cell death in the lateralstriatum.3. A very early state of neuronal damage was detected by argyrophil III silverimpregnation.4. Estrogen protected against while testosterone exacerbated the striatal lesionsinduced by 3-NPA.5. Fetal striatal cells were transplanted into the injured striatum one month afterNPA intoxication. Once the cells survived，他们extended neurites in the host striatum and resulted in the improvement of the motorsymptom.6. After 3-NPA应用程序in vitro，astrocytes were more sensitive than neurons in the increase of [Ca D2i ++ D2i D2，and they got into necrotic cell death.7. bFGFthrombin and melatonin protected in vitro astrocytic cell death induced by the application of 3-NPA，nitroprusside （NO donor）或serum-free medium。

Systemic administration of 3-nitropropionic acid (3-NPA, 20 mg/kg, s.c., daily, 2 or 3 days) to rats induced striatum selective lesions, and animals manifested motor symptoms. In the present study, we analyzed the mechanisms of the striatal vulnerability and tried to protect the damage.Results are as follows.1. 3-NPA intoxication induces the depletion of ATP thus leading to the depolarization of the cell membrane and release of glutamate. The depolarization and the excess amount of glutamate induce neuronal cell death in the center of the striatum.2. The depolarization also induces the excess release of dopamine (DA) that leads to neuronal and astroglial cell death in the lateral striatum.3. A very early state of neuronal damage was detected by argyrophil III silver impregnation.4. Estrogen protected against while testosterone exacerbated the striatal lesions induced by 3-NPA.5. Fetal striatal cells were transplanted into the injured striatum one month after 3-NPA intoxication. Once the cells survived, they extended neurites into the host striatum and resulted in the improvement of the motor symptom.6. After 3-NPA application in vitro, astrocytes were more sensitive than neurons in the increase of [CaィイD1++ィエD1]ィイD2iィエD2, and they got into necrotic cell death.7. bFGF, thrombin and melatonin protected in vitro astrocytic cell death induced by the application of 3-NPA, sodium nitroprusside (NO donor) or serum-free medium.