This study investigated the proliferation and differentiation of adult neural progenitor cells (aNPCs) derived from the striatum and substantianigra (SN) of parkinsonian rats. We found that aNPCs isolated from the two areas of parkinsonian rats readily formed nestin-enrichedneurospheres in vitro and exhibited an ability to differentiate into either neurons or astrocytes. Injection of epidermal growth factor (EGF)and basic fibroblast growth factor (bFGF) into the striatum of parkinsonian rats prior to the harvesting striatal aNPCs significantly increasedthe neurosphere formation rate and multiple differentiation capacity of these aNPCs when cultured in vitro. These data suggest that striataland nigral adult NPCs in parkinsonian rats retain the abilities of proliferation and differentiation in vitro. In addition, exogenously appliedgrowth factors could up-regulate the developmental potential of aNPCs. We conclude that our data supports the notion that endogenous cellreplacement therapies may be useful for the future treatment of Parkinson’s disease (PD).

Neurotrophic factors, such as nerve growth factorand brain-derived neurotrophic factor, are members of thestructurally related neurotrophin family that play importantroles in pain modulation. Although there are also indicationsfor the involvement of glial cell line-derived neurotrophicfactor (GDNF), it is unclear whether and how GDNF is involvedin inflammatory pain. In the present study, we studiedthe expression pattern of GDNF in dorsal root ganglia (DRG)and spinal cord, using confocal microscopy. We demonstratethat GDNF is well associated with nonpeptidergic pain pathwayand that GDNF could possibly be anterogradely transportedfrom DRG neurons to superficial spinal cord dorsalhorn. We also studied the dynamic changes of GDNF expressionin rats during chronic inflammation using injection ofcomplete Freund's adjuvant as a model of chronic pain. Wefound that GDNF was down-regulated in both dorsal rootganglia and spinal cords 2 weeks after arthritis induction. Toassess the impact of this down-regulation on pain transmission,we used a function-blocking antibody against GDNFdelivered intrathecally in the same chronic-pain animal models.Injection of this antibody to GDNF produced no immediateeffect, but decreased the delayed, bilateral hyperalgesiainduced from a unilateral injection of complete Freund’s adjuvant.The effect of this antibody coincided with the downregulationof GDNF immunoreactivity in response to inflammation,suggesting that GDNF supports biochemicalchanges that contribute to hyperalgesia. © 2003 IBRO. Publishedby Elsevier Science Ltd. All rights reserved.

Low and high frequency electro-acupuncture (EA) stimulationwas used in rats that had been lesioned by medial forebrain bundle transection. Behavioral tests showed that both low and high frequency EA stimulation signi

Mounting lines of evidence have suggested that brain inflammation participates in the pathogenesis of Parkinson's disease. Triptolide is oneof the major active components of Chinese herb Tripterygium wilfordii Hook F, which possesses potent anti-inflammatory andimmunosuppressive properties. We found that triptolide concentration-dependently attenuated the lipopolysaccharide (LPS)-induced decreasein [3H]dopamine uptake and loss of tyrosine hydroxylase-immunoreactive neurons in primary mesencephalic neuron/glia mixed culture.Triptolide also blocked LPS-induced activation of microglia and excessive production of TNFa and NO. Our data suggests that triptolide mayprotect dopaminergic neurons from LPS-induced injury and its efficiency in inhibiting microglia activation may underlie the mechanism.D 2003 Elsevier B.V. All rights reserved.

It has been reported recently that the immunosuppressant FK506 produced neurotrophic and neuroprotective effects on dopaminergic neurons in vitro and in vivo. We investigated whether tripchlorolide, an immunosuppressive extract of Chinese herb Tripterygium wilfordii Hook F, could exert similar neurotrophic and neuroprotective effects similar to those of FK506. It was found that tripchlorolide promoted axonal elongation and protected dopaminergic neurons from a neurotoxic lesion induced by 1-methyl-4-phenylpyridinium ion (MPP+) at concentrations of as low as 10-12 to 10-8 M. In situ hybridization study revealed that tripchlorolide stimulated brain-derived neurotrophic factor (BDNF) mRNA expression. In vivo administration of tripchlorolide (1ug/kg, ip) for 28 days effectively attenuated the rotational behavior challenged by D-amphetamine in the model rats by transection of the medial forebrain bundle. In addition, tripchlorolide treatment (0.5 or 1ug/kg/day for 28 days) increased the survival of dopaminergic neurons in substantia nigra pars compacta by 50 and 67%, respectively. Moreover, tripchlorolide markedly prevented the decrease in amount of dopamine in the striatum of model rats. Taken together, our data provide the first evidence that tripchlorolide acts as a neuroprotective molecule that rescues MPP+ or axotomy-induced degeneration of dopaminergic neurons, which may imply its therapeutic potential for Parkinson’s disease. The underlying mechanism may be relevant to its neurotrophic effect and its efficacy in stimulating the expression of BDNF.