Selective blockade of the rat brain aqueduct with thermogelling hydrogel nanoparticle dispersion.
Experimental methods targeting molecules or drugs to specific neuronal tissue(s) can be important in determining function. In this study we focused on blockade of the small channel or aqueduct connecting the third and fourth ventricles of the rat brain. A cannula was placed into the aqueduct between the third and fourth ventricle. A second cannula was placed into the third or fourth ventricle. An aqueous dispersion of hydrogel nanoparticles, that maintains a liquid state at temperatures below 33 degrees C and solidifies near body temperature (35 degrees C), was infused into the aqueduct. Two interpenetrating polymer networks (IPN) of hydrogel nanoparticles with polymer concentrations at 2% by weight and 3% by weight were separately infused into the aqueduct to block cerebrospinal fluid (CSF) flow. Following infusion of hydrogel CSF was isolated to a particular ventricle as shown by the lack of dye movement between the ventricles. In addition, stress hormone, corticosterone, feeding behavior and blood glucose levels were measured. Results show upon reaching the aqueduct the hydrogel dispersion solidified and restricted the flow of CSF. A higher concentration of dispersion (3% wt.) was more effective in blocking the aqueduct and isolating the third from the fourth ventricle. Over the period of measurement, infusion of the dispersion had no measurable detrimental physiological effects on the animal. We conclude that isolation of ventricles in the brain can be completed for 48-h by using dispersions of hydrogel nanoparticles and the effects of drugs on certain brain tissues can be determined with this method.
Kramer
Phillip R
PR
Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M University System Health Science Center, Dallas, TX 75246, USA. pkramer@bcd.tamhsc.edu <pkramer@bcd.tamhsc.edu>
Guan
Guoqiang
G
Zhou
Jun
J
Hu
Zhibing
Z
Bellinger
Larry L
LL
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology*; D002535:Cerebral Aqueduct / Q000187:drug effects* / Q000502:physiology; D003345:Corticosterone / Q000134:cerebrospinal fluid; D005247:Feeding Behavior / Q000187:drug effects; D020546:Fourth Ventricle / Q000187:drug effects / Q000502:physiology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020542:Third Ventricle / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D001786:Blood Glucose; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003345:Corticosterone