The lazaroid U-83836E improves the survival of rat embryonic mesencephalic tissue stored at 4 degrees C and subsequently used for cultures or intracerebral transplantation.
We assessed the effects of addition of the lazaroid U-83836E to a preservation medium on the survival of rat dopamine neurons stored before culturing or intracerebral transplantation. Embryonic ventral mesencephalic tissue was preserved at 4 degrees C for 8 days with or without the addition of 0.3 mu M of U-83836E to a chemically defined "hibernation" medium. Freshly dissected mesencephalic tissue was used in control groups. For culture experiments, the mesencephalic tissue was dissociated and grown in serum-containing medium. Following 24-48 h in vitro, the number of dopamine neurons in cultures derived from tissue hibernated without the lazaroid was 40% of fresh control, compared with 67% of control in cultures prepared from tissue stored in the presence of U-83836E. When mesencephalic tissue was transplanted to the dopamine-depleted striatum of hemiparkinsonian rats following 8 days storage at 4 degrees C in a medium without U-83836E, the mean number of surviving dopamine neurons in the grafts was significantly reduced to 40% of control. In contrast, grafts of tissue which had been hibernated in U-83836E-containing medium contained as many dopamine neurons as transplants of freshly dissected tissue. High yields of surviving grafted dopamine neurons were correlated to a significantly faster onset of functional recovery of amphetamine-induced motor asymmetry. We conclude that the storage period for rat mesencephalic tissue can be prolonged up to 8 days when using lazaroid-supplemented hibernation medium. As lazaroids have undergone clinical safety testing, the application of lazaroids for tissue storage in clinical transplantation trials can be envisaged.
Grasbon-Frodl
E M
EM
Section for Neuronal Survival, Department of Physiology and Neuroscience, University of Lund, Sweden.
Nakao
N
N
Brundin
P
P
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D015925:Cryopreservation; D004298:Dopamine / Q000032:analysis; D005260:Female; D016332:Fetal Tissue Transplantation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008636:Mesencephalon / Q000187:drug effects* / Q000196:embryology / Q000637:transplantation; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000737:chemistry / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation
D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D010879:Piperazines; C066382:U 78517F; D004298:Dopamine