GABA receptor agonist promotes reformation of the striatonigral pathway by transplant derived from fetal striatal primordia in the lesioned striatum.
Striatal lesions are known to cause the anterograde transneuronal degeneration of the substantia nigra pars reticulata (SNr) neurons in consequence to loss of GABAergic inhibitory striatonigral efferents. The present study was undertaken to examine whether long-term intraventricular administration of the GABA agonist muscimol could promote reformation of the striatonigral pathway arising from transplants by rescuing host SNr neurons from transneuronal death in rats with striatal ischemic lesions. Compared to nongrafted rats with striatal lesions, (i) a prominent axonal projection from the transplants to the ipsilateral substantia nigra, (ii) a significant increase in number of survived neurons in the ipsilateral SNr, and (iii) a significant reduction in number of apomorphine-induced turning behaviors were found in grafted animals with muscimol infusion, but not in those without muscimol administration. These findings suggest that preservation of the host target neurons for grafted cells may increase an efficacy of cerebral implants in establishment of the host-graft fiber connections, possibly, leading to functional restoration.
Goto
S
S
Department of Neurosurgery, Kumamoto University Medical School, Japan.
Yamada
K
K
Yoshikawa
M
M
Okamura
A
A
Ushio
Y
Y
D000818:Animals; D001058:Apomorphine / Q000633:toxicity; D001925:Brain Damage, Chronic / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000150:complications; D016380:Brain Tissue Transplantation / Q000473:pathology; D002452:Cell Count; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003342:Corpus Striatum / Q000187:drug effects* / Q000196:embryology / Q000473:pathology / Q000637:transplantation*; D016332:Fetal Tissue Transplantation / Q000473:pathology; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015918:Infusion Pumps, Implantable; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000473:pathology*
D018755:GABA Agonists; D018696:Neuroprotective Agents; D018079:Receptors, GABA; D009118:Muscimol; D001058:Apomorphine