TY - JOUR
T1 - Systemic treatment with GM1 ganglioside improves survival and function of cryopreserved embryonic midbrain grafted to the 6-hydroxydopamine-lesioned rat striatum
AU - Sautter, J.
AU - Höglinger, G. U.
AU - Oertel, W. H.
AU - Earl, C. D.
N1 - Funding Information:
We thank Petra Renner and Josephine März for excellent animal care and technical assistance. This research was supported by BMFT (01KI9001) and the “Gemeinnützige Hertie-Stiftung” (GHS 3000/96). GM1 was kindly provided by Fidia Pharmaceuticals, Abano Terme, Italy.
PY - 2000/7
Y1 - 2000/7
N2 - Cryopreservation may allow long-term storage of embryonic ventral mesencephalon (VM) for neural transplantation. We investigated whether the ganglioside GM1 or the lazaroid tirilazad mesylate (U-74006F) could improve survival of grafts derived from cryopreserved VM in a rat model of Parkinson's disease. VM was dissected from rat embryos (E14-E15), frozen and stored in liquid nitrogen under controlled conditions, thawed, dissociated, and then grafted into the 6-hydroxydopamine-lesioned rat striatum. In Experiment I, VM fragments were exposed in vitro either to GM1 (100 μM)) or to lazaroid (0.3 μM) during all preparative steps. In Experiment II, rats receiving GM1-pretreated VM were, in addition, treated systematically with GM1 (30 mg/kg) daily for 3.5 weeks. Rats grafted with untreated cryopreserved or fresh VM were used as controls, respectively. Rats receiving fresh VM control grafts showed complete recovery from lesion-induced rotations after 6 weeks whereas rats grafted with cryopreserved VM (untreated or pretreated) did not recover. Cryografts contained significantly less (18%, control; 23%, GM1; and 12%, lazaroid) tyrosine hydroxylase-positive cells compared to fresh grafts (1415 ± 153; mean ± SEM). Graft volume was also significantly smaller after cryopreservation. In contrast, with additional systemic GM1 treatment cryografts contained almost the same number of tyrosine hydroxylase-positive cells (376 ± 85) as fresh grafts (404 ± 56), which was significantly more than that of untreated cryografts (147 ± 20), showed a significantly larger volume (0.15 mm3) compared to that of untreated grafts (0.08 mm3) (fresh controls, 0.19 mm3), and induced significant and complete functional recovery in the rotation test. In conclusion, systemic treatment of rats with GM1 improved the low survival and functional inefficacy of grafts derived from cryopreserved VM whereas tissue pretreatment alone with either GM1 or lazaroid was not effective. (C) 2000 Academic Press.
AB - Cryopreservation may allow long-term storage of embryonic ventral mesencephalon (VM) for neural transplantation. We investigated whether the ganglioside GM1 or the lazaroid tirilazad mesylate (U-74006F) could improve survival of grafts derived from cryopreserved VM in a rat model of Parkinson's disease. VM was dissected from rat embryos (E14-E15), frozen and stored in liquid nitrogen under controlled conditions, thawed, dissociated, and then grafted into the 6-hydroxydopamine-lesioned rat striatum. In Experiment I, VM fragments were exposed in vitro either to GM1 (100 μM)) or to lazaroid (0.3 μM) during all preparative steps. In Experiment II, rats receiving GM1-pretreated VM were, in addition, treated systematically with GM1 (30 mg/kg) daily for 3.5 weeks. Rats grafted with untreated cryopreserved or fresh VM were used as controls, respectively. Rats receiving fresh VM control grafts showed complete recovery from lesion-induced rotations after 6 weeks whereas rats grafted with cryopreserved VM (untreated or pretreated) did not recover. Cryografts contained significantly less (18%, control; 23%, GM1; and 12%, lazaroid) tyrosine hydroxylase-positive cells compared to fresh grafts (1415 ± 153; mean ± SEM). Graft volume was also significantly smaller after cryopreservation. In contrast, with additional systemic GM1 treatment cryografts contained almost the same number of tyrosine hydroxylase-positive cells (376 ± 85) as fresh grafts (404 ± 56), which was significantly more than that of untreated cryografts (147 ± 20), showed a significantly larger volume (0.15 mm3) compared to that of untreated grafts (0.08 mm3) (fresh controls, 0.19 mm3), and induced significant and complete functional recovery in the rotation test. In conclusion, systemic treatment of rats with GM1 improved the low survival and functional inefficacy of grafts derived from cryopreserved VM whereas tissue pretreatment alone with either GM1 or lazaroid was not effective. (C) 2000 Academic Press.
KW - Cryopreservation
KW - Embryonic dopamine cells
KW - Lazaroid
KW - Parkinson's disease
KW - Transplantation
KW - Ventral mesencephalon
UR - http://www.scopus.com/inward/record.url?scp=0343081424&partnerID=8YFLogxK
U2 - 10.1006/exnr.2000.7410
DO - 10.1006/exnr.2000.7410
M3 - Article
C2 - 10877922
AN - SCOPUS:0343081424
SN - 0014-4886
VL - 164
SP - 121
EP - 129
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -