Microglia are believed to participate in the mediation of neurodegeneration through producing a variety of cytotoxic factors upon activation. Pharmacological intervention inmicroglial activation may therefore exert a neuroprotective effect. In exploring pharmacological agents that can effect microglial activation, we found in this study that triptolide possesses a powerful inhibitory influence over microglia. Pretreatment with triptolide was able to dose-dependently reduce the lipopolysaccharide (LPS)-induced nitrite accumulation and tumor necrosis factor-a and interleukin-1

Electroacupuncture (EA) has been used in China for many years to treat Parkinson’s disease (PD) with reportedly effective results. However, the physiological and biological mechanism behind its effectiveness is still unknown. In the present study, different frequencies of chronic EA stimulation (0, 2, 100 Hz) were tested in a partially lesioned rat model of PD which was induced by transection of the medial forebrain bundle (MFB). After 24 sessions of EA stimulation (28 days after MFB transection), dopaminergic neurons in the ventral midbrain were examined by immunohistochemical staining, and brain-derived neurotrophic factor (BDNF) mRNA levels in ventral midbrain were measured by in situ hybridization. The results show a marked decrease of dopaminergic neurons on the lesioned side of the substantia nigra (SN) comparing with the unlesioned side. Zero Hz and 2 Hz EA stimulation had no effect on the disappearance of dopaminergic neurons. However, after 100 Hz EA, about 60% of the tyrosine hydroxylase (TH)-positive neurons remained on the lesioned side of the SN. In addition, levels of BDNF mRNA in the SN and ventral tegmental area (VTA) of the lesioned side were significantly increased in the 100 Hz EA group, but unchanged in the 0 and 2 Hz groups. Our results suggest that long-term high-frequency EA is effective in halting the degeneration of dopaminergic neurons in the SN and up-regulating the levels of BDNF mRNA in the subfields of the ventral midbrain. Activation of endogenous neurotrophins by EA may be involved in the regeneration of the injured dopaminergic neurons, which may underlie the effectiveness of EA in the treatment of PD.

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