Striatal grafts provide sustained protection from kainic and quinolinic acid-induced damage.
Grafts of neonatal striatal tissue were placed into the striata of adult rats. When challenged immediately with intrastriatal injections of either kainic or quinolinic acid, excitotoxic damage was prevented. Thirty days later these same graft recipients received another injection of excitotoxin. The intrastriatal grafts continued to mitigate toxin-induced damage. It is hypothesized that the grafted cells not only survive, but that they may continue to elaborate some substance or substances that prevent excitotoxin-induced injury for at least 30 days. Previous investigations indicated that grafts of neonatal striatal tissue can protect the recipient striatum from kainic acid toxicity. In the following study it is demonstrated that such grafts also protect the striatum from quinolinic acid, an endogenous excitotoxin which induces kainate-like neuronal degeneration and has been implicated in the pathogenesis of Huntington's disease. It is postulated that the salutary effect of striatal grafting may be sufficiently long lasting to mitigate a chronic toxic insult. Such grafting may therefore represent a therapy for Huntington's disease and other neurodegenerative disorders in which an endogenous or exogenous toxin has been implicated as the pathogenetic agent.
Tulipan
N
N
Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Luo
S Q
SQ
Allen
G S
GS
Whetsell
W O
WO
D000818:Animals; D000831:Animals, Newborn; D001927:Brain Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D007608:Kainic Acid / Q000494:pharmacology / Q000633:toxicity*; D009474:Neurons / Q000473:pathology; D011725:Pyridines / Q000633:toxicity*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
D011725:Pyridines; D011805:Quinolinic Acids; D017378:Quinolinic Acid; D007608:Kainic Acid