Effects of Nano-MnO2 on dopaminergic neurons and the spatial learning capability of rats.

This study aimed to observe the effect of intracerebrally injected nano-MnO2 on neurobehavior and the functions of dopaminergic neurons and astrocytes. Nano-MnO2, 6-OHDA, and saline (control) were injected in the substantia nigra and the ventral tegmental area of Sprague-Dawley rat brains. The neurobehavior of rats was evaluated by Morris water maze test. Tyrosine hydroxylase (TH), inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) expressions in rat brain were detected by immunohistochemistry. Results showed that the escape latencies of nano-MnO2 treated rat increased significantly compared with control. The number of TH-positive cells decreased, GFAP- and iNOS-positive cells increased significantly in the lesion side of the rat brains compared with the contralateral area in nano-MnO2 group. The same tendencies were observed in nano-MnO2-injected rat brains compared with control. However, in the the positive control, 6-OHDA group, escape latencies increased, TH-positive cell number decreased significantly compared with nano-MnO2 group. The alteration of spatial learning abilities of rats induced by nano-MnO2 may be associated with dopaminergic neuronal dysfunction and astrocyte activation.

Signaling of glial cell line-derived neurotrophic factor and its receptor GFRα1 induce Nurr1 and Pitx3 to promote survival of grafted midbrain-derived neural stem cells in a rat model of Parkinson disease.

Glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 have been implicated in the survival of ventral midbrain dopaminergic (DA) neurons, but the molecular mechanisms bywhich GDNF generates DA neurons in grafted midbrain-derived neural stem cells (mNSCs) are not understood. Midbrain-derived neural stem cells isolated from rat embryonic mesencephalon (embryonic day 12) were treated with GDNF or in combination with GFRα1 small interfering RNA. Reverse transcription-polymerase chain reaction, Western blot, and immunocytochemistry were used totest the expression of the orphan nuclear receptor Nurr1 and thetranscription factor Pitx3 and newborn tyrosine hydroxylase (TH)-positive cells. Treatment of mNSCs with GDNF increased mNSCs' sphere diameter, reduced expression of caspase 3, and increased expression of Bcl-2. Glial cell line-derived neurotrophic factor-treated mNSCs enhanced Nurr1 and Pitx3 expression and the fraction of TH-, TH/Pitx3-, and TH/Nurr1-positive cells in culture. Grafted GDNF-treated mNSCs significantly decreased apomorphine-induced rotation behavior in 6-hydroxydopamine-lesioned rats. Glialcell line-derived neurotrophic factor-treated mNSCs showed increased numbers of TH/Pitx3- and TH/Nurr1-postivie cells. The effect elicited by GDNF was inhibited by small interfering RNA-mediated knockdown of GFRα1. Our data demonstrate the contribution of GDNF to DA neuron development and may also elucidate pathogenetic mechanisms in Parkinson disease and contribute to the development of novel therapies for the disorder.

[Parthenolide inhibits neuroinflammation and promotes neurogenesis in the ischemic striatum following transient middle cerebral artery occlusion in the adult rat brain].

AIM: The objective of this study was to test the hypothesis that parthenolide suppresses ischemia-induced neuroinflammation in the MCAO model of adult rat. METHODS: MCAO rats were treated i.p. with parthenolide (500 microg/kg). Brain sections were analyzed for BrdU, BrdU-DCX, BrdU-Tuj-1, BrdU-MAP-2 and BrdU-GFAP staining. Total protein was extracted from ischemic striatum, and Western blot was used to determine TNF-alpha expression. RESULTS: Cerebral ischemia increases expression of TNF-alpha in the ischemic striatum. Parthenolide suppressed the expression of TNF-alpha and enhances the proliferation of newborn cells in the ischemic striatum. The cell number of BrdU(+)-DCX(+), BrdU(+)-Tuj-1(+), and BrdU(+)-MAP-2(+) is increased in the ischemic striatum after parthenolide treatment at 3 d, 7 d or 28 d after MCAO. Furthermore, parthenolide depressed the cell number of BrdU(+)-GFAP(+) in the ischemic striatum at 3 d, 7 d and 28 d after MCAO. CONCLUSION: Parthenolide inhibits neuroinflammation induced by cerebral ischemia and promotes neurogenesis in the ischemic striatum. Further study of the effects of parthenolide on inflammatory gene expression using model animal systems as described here are critical to elucidating their mechanisms of action.

[Experimental research on immunological rejection in neural stem cells allograft].

AIM: To investigate the occurrence of immunological rejection in brain transplantation of neural stem cells (NSCs) in the rat of Parkinson's disease model. METHODS: NSCs derived from the brain of E14.5d SD rat were cultured in vitro. Single cell suspensions were grafted into the striatum of the rat model of Parkinson's disease. Surviving animals were sacrificed at 10, 21, 35 and 60 d after transplantation, and the brain tissue was stained with HE and immunocytochemically to detect the expression of tyrosine hydroxylase (TH), CD4, CD8 and major histocompatibility complex class II antigens (MHC-II). RESULTS: The expression of elicited CD4, CD8 and MHC-II was detected within and around the allografts in the graft groups at 10 and 21 d after grafting and was subsiding at 35 d. At 60 d only very occasional immunopositive cells were present. The number of TH positive neurons was low at 10, 21 d, but increased at 35 d and 60 d. There was no significant difference between negative and positive control groups at different time points. The rotation behavior of PD was decreased 35 d after transplantation. CONCLUSION: Intracerebral transplantation of NSCs did not cause remarkable immunological rejection.

[Experimental research on immunological rejection of brain tissue allograft].

AIM: To investigate the occurrence of rejection in brain tissue transplantation. METHODS: Ventral mesencephalon(VM) single cell suspensions from newborn rats were allografted into the striata of Parkinson's disease model recipient rats. Surviving animals were sacrificed at 2, 4 and 6 wk after transplantation, and the brain tissues were stained with HE or immunocytochemically to inspect the expression of tyrosine hydroxylase (TH) and major histocompatibility complex class II antigens (MHC II). RESULTS: High MHC II expression was observed within and around the allografts compared with control at 2 wk after grafting. MHC II expression then decreased at 4 wk and at 6 wk only few immunopositive cells remained. The number of TH positive neurons was low at 2 wk, but increased at 4 and 6 wk after transplantation. CONCLUSION: The brain is not an "immunologically privileged site" and graft rejection exists in brain tissue transplantation. This rejection maybe induced by MHC II. Therefore it is necessary to use immunosuppressants in brain transplantation.