Striatal grafts in infarct striatopallidum increase GABA release, reorganize GABAA receptor and improve water-maze learning in the rat.
We grafted fetal striatal cells in ischemic rat models, and investigated graft survival/growth, GABA release, GABAA receptor reorganization and functional recovery. One hour intraluminal occlusion of the middle cerebral artery (MCA) induced ischemic infarct in the lateral part of the striatum and adjacent cortex. In ischemic rats, the acquisition of Morris' water-maze learning was significantly slower than that of control rats. In these animals GABA level in the globus pallidus, detected by microdialysis, was about the half of that of controls. However, after the grafts of fetal striatal cells in the striatopallidum, the acquisition was improved, thus no difference was observed in the time course of learning curves in control and grafted animals. GABA level recovered to almost normal level by the graft. It further increased by the treatment of a GABA uptake blocker (nipecotic acids) in the perfusion. In the grafts, GABAA receptor organization detected by autoradiography using [3H] labeled SR95531 was restored for more than 1 year after the graft. Data suggest that fetal striatal cell grafts in infarct striatum may partially reconstruct striatopallidal GABA projection and reorganize GABAA receptor. This might be a basis of improvement of function.
Aihara
N
N
Department of Neurosurgery, Nagoya City University Medical School, Japan.
Mizukawa
K
K
Koide
K
K
Mabe
H
H
Nishino
H
H
D000818:Animals; D001345:Autoradiography; D002545:Brain Ischemia / Q000503:physiopathology / Q000523:psychology; D016380:Brain Tissue Transplantation / Q000502:physiology*; D017690:Cell Transplantation / Q000502:physiology*; D002536:Cerebral Arteries / Q000502:physiology; D002544:Cerebral Infarction / Q000503:physiopathology / Q000523:psychology; D058787:GABA-A Receptor Antagonists; D005917:Globus Pallidus / Q000502:physiology* / Q000503:physiopathology; D007858:Learning / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000502:physiology / Q000503:physiopathology / Q000637:transplantation*; D009557:Nipecotic Acids / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D058787:GABA-A Receptor Antagonists; D009557:Nipecotic Acids; D011724:Pyridazines; D011963:Receptors, GABA-A; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D011392:Proline; C010983:homoproline