Unilateral implantation of dopamine-loaded biodegradable hydrogel in the striatum attenuates motor abnormalities in the 6-hydroxydopamine model of hemi-parkinsonism.
Dopaminergic functional recovery following controlled release of dopamine from biodegradable polymer matrices implanted in the lesioned striatum was investigated in a hemiparkinsonian animal model. Significant dopamine depletion in the striatum ipsilateral to the side of infusion was observed in animals unilaterally infused with 6-hydroxydopamine (6-OHDA) in the substatia nigra. These animals displayed apomorphine-induced contralateral rotational behavior, when examined on the 16th day. Implantation of a controlled release delivery system (hydrogel obtained by mixing dextran dialdehyde cross-linked with gelatin) containing dopamine in the denervated striatum on the 1st day or the 18th day significantly abolished the apomorphine-induced contralateral rotational behavior in these animals. The recovery was visible for about 17 days, thereafter the behavioral bias reappeared. The present results indicate that dopamine released from the polymer matrices alleviates behavioral bias in experimental parkinsonism, implying use of such technologies as an alternative method for the treatment of Parkinson's disease. This approach is useful in reducing the oral dose of drugs that are with severe systemic effects, and that develop tolerance.
Senthilkumar
Karuppagounder S
KS
Division of Cell Biology & Physiology, Laboratory of Clinical & Experimental Neuroscience, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, India.
Saravanan
Karuppagounder S
KS
Chandra
Goutam
G
Sindhu
Kizhakke M
KM
Jayakrishnan
A
A
Mohanakumar
Kochupurackal P
KP
D020341:Absorbable Implants; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004347:Drug Interactions; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test / Q000379:methods; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine