Continuous intraventricular drug infusion for the in vivo study of transneuronal degeneration in the striatonigral system of the rat.
Injuries to certain parts of the brain may induce neuronal death in distant areas innervated by the sites of the primary lesion. Such characteristic pathological changes, known as anterograde transneuronal degeneration, may occur at the next and more distant synaptic levels and play a part in the slow progression of some types of system degeneration. Delayed transneuronal degeneration of the substantia nigra pars reticulata (SNr) is one example of this form of cell death, and it occurs as a consequence of a neostriatal lesion caused by focal ischemia, Huntington's disease, or experimental axon-sparing injections of neurotoxin. Ever since the demonstration by Saji and Reis that the administration of GABA receptor agonist effectively prevented delayed transneuronal degeneration of the SNr, the degeneration of nigral reticulata cells has been attributed to the loss of striatal inhibition (Fig. 1A). The latter process severely upset the balance of membrane potential of nigral reticulata cells, producing an effect resembling excitotoxicity. In this report, we describe a continuous intraventricular MK-801 infusion technique that is useful in clarifying the role of glutamatergic action via N-methyl-D-aspartate (NMDA) receptor subclasses involved in exo-focal postischemic death of the SNr.
Yamada
K
K
Department of Neurosurgery, Kumamoto University Medical School, Japan.
Goto
S
S
Yoshikawa
M
M
Okamura
A
A
Ushio
Y
Y
D000818:Animals; D001284:Atrophy; D001831:Body Temperature / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D003342:Corpus Striatum / Q000473:pathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007260:Infusion Pumps; D007276:Injections, Intraventricular; D008297:Male; D009410:Nerve Degeneration / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*
D018696:Neuroprotective Agents; D016291:Dizocilpine Maleate