Blood-brain barrier unlocked.
The brain is protected by a physiological blood-brain barrier (BBB) against toxins and some metabolites circulating in the blood. At the same time, the BBB limits penetration into the brain of many neuroactive drugs. Efficient ways to increase BBB permeability for delivery of drugs of different chemical nature into the brain are unknown. This work deals with delivery into the brain of 10(-2) M dopamine, a substance that does not penetrate the BBB under normal circumstances. It was studied in two independent experiments: (i) penetration of (3)H-labeled dopamine from its mixture with 10(-5) M H2O2 into hypothalamus and striatum structures of intact rat brain, and (ii) effect of unlabeled dopamine from a mixture with H(2)O(2) on the rat motor activity in a haloperidol catalepsy model. It was shown that (i) at the third minute after nasal application of the dopamine + H(2)O(2) mixture, the dopamine level increases 45-fold in the hypothalamus and almost 30-fold in the striatum and (ii) motility of animals in the catalepsy haloperidol model is recovered 90 sec after intranasal introduction of dopamine. No such effects were observed after replacement of H(2)O(2) by 0.9% NaCl solution. Thus, it was shown on the example of dopamine that its introduction into the nasal cavity simultaneously with H(2)O(2) provides for rapid delivery of the drug into the brain. These results expand our knowledge concerning the biological role of exoROS in modulating BBB permeability and may contribute to the development of a new therapeutic strategy for neurological diseases.
Department of Human and Animal Physiology, Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia. dr.naum.goldstein@googlemail.com
N
N
Goldstein
R
R
Goldstein
D
D
Terterov
A A
AA
Kamensky
G I
GI
Kovalev
Yu A
YA
Zolotarev
G N
GN
Avakyan
S
S
Terterov
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis / Q000494:pharmacology; D015259:Dopamine Agents / Q000032:analysis / Q000494:pharmacology; D006220:Haloperidol / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D007553:Isotope Labeling; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014316:Tritium / Q000737:chemistry
D015259:Dopamine Agents; D017382:Reactive Oxygen Species; D014316:Tritium; D015102:3,4-Dihydroxyphenylacetic Acid; D006861:Hydrogen Peroxide; D006220:Haloperidol; D004298:Dopamine