[Therapeutic study of autologous Schwann cells' bridge graft into the brain of hemiparkinsonian monkey].
OBJECTIVE
To evaluate the therapeutic effect of autologous transplantation of Schwann cells as "bridge" between the medial forebrain bundle (MFB) and caudate nucleus, into the brain of hemiparkinsonian monkey.


METHODS
Six monkeys were used following 6-OHDA-induced hemiparkinsonism. Three of them were autologous transplanted using Schwann cells as "bridges" between MFB and caudate nucleus. The Schwann cells were pre-treated using Hoechst33342. The other three monkeys received sham operation as controls. All the monkeys received behavioral assessment. The metabolism of dopamine was measured by SPECT using (99)Tcm-TRODAT-1 and PET using 18F-FP-beta-CIT. After a 4-month follow-up, the monkeys' brain were removed from the skull, fixed in 4% paraformaldehyde and cut into serial sections. A fluorescence microscope examination and a tyroxine hydroxylase (TH) immunohistochemistry study were made on the sections. Cell types were determined by double staining. The level of TH protein around the needle track was determined by Western blotting.


RESULTS
All three monkeys, which had undergone Schwann cells autologous bridge graft showed a decrease in the disability score and two of them had an increase in motor activity. The apomorphine evoked rotation was also decreased. The symptoms of the monkeys, which received sham operation, had not amelioration. In SPECT examination, the radioactivity count was greatly increased in the grafted monkeys. The dopamine levels were significantly increased in the caudate nucleus from 61% (before graft) to 79% (after graft) while there's no change in control group. In histological examination, autologous Schwann cells could survive and migrate in the brain. Around the Schwann cells "bridge", there were numerous TH positive short fibers in the MFB area. Around the whole length of the "bridge", there were a lot of TH positive reactive astrocytes, especially in thalamus. TH protein around the needle track of the graft group was 243% compared with that of control group.


CONCLUSIONS
Autologous Schwann cells bridge graft is a feasible technique with therapeutic effects on parkinson disease monkeys. The Schwann cells play an important role in dopaminergic axonal elongation and in inducing the TH positive phenotype of reactive astroglia cell around it.
Xu
Bin
B
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Jiang
Cheng-chuan
CC
Zhang
Li
L
Li
Bao-ming
BM
Chen
Zheng-ping
ZP
Guan
Yi-hui
YH
Liu
Xing-dang
XD
Zhang
Fu-lin
FL
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D000882:Haplorhini; D008856:Microscopy, Fluorescence; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D012583:Schwann Cells / Q000637:transplantation*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine