An improved device for continuous intraventricular infusions prevents the introduction of pump-derived toxins and increases the effectiveness of NGF treatments.
The recent demonstrations of the ability of nerve growth factor (NGF) to protect and promote the welfare of certain cholinergic neurons in the adult CNS have increased the need for safe, accurate, and reliable procedures for intracerebral administration of protein and other experimental agents. Osmotic minipumps have been used to infuse NGF into the lateral ventricle of adult rats, but a sustained and harmless performance of such infusions has not been fully evaluated. The study reported here has led to (i) the recognition that cytotoxic substances, released from some minipumps into the infusion fluid, may be responsible for various degrees of periventricular tissue damage, and (ii) the redesigning of an infusion device which, among other modifications, uses the osmotic pump to propel infusion fluid into the ventricle but prevents pump-derived materials from entering the infusate itself. Besides several other advantages, the modified infusion device has permitted the demonstration that NGF can fully protect experimentally axotomized medial septum cholinergic neurons and can do so with less variability than previously observed and without creating tissue damage.
Department of Biology, University of California, San Diego, La Jolla 92093.
H L
HL
Vahlsing
S
S
Varon
T
T
Hagg
B
B
Fass-Holmes
A
A
Dekker
M
M
Manley
M
M
Manthorpe
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology*; D004867:Equipment Design; D005260:Female; D007260:Infusion Pumps; D007263:Infusions, Parenteral / Q000295:instrumentation / Q000379:methods; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014118:Toxins, Biological / Q000032:analysis* / Q000494:pharmacology
D009414:Nerve Growth Factors; D014118:Toxins, Biological