Oligodeoxynucleotides induce brain inflammation in rats when infused intracerebroventricularly.
Antisense oligodeoxynucleotides (ODNs) can inhibit gene expression in a specific manner. However, several studies described problems with cerebral ODN application. Here, we investigated the immune effects (interleukin-6 (IL-6) release, cell invasion into cerebrospinal fluid (CSF) and brain parenchyma) of 'non-sense' randomized ODNs with different counterions (NH(4)(+), Na(+)) and modifications (with or without thioat-backbone) which were administered intracerebroventricularly for 48 h using osmotic mini-pumps in a rat model. All animals receiving ODNs showed increased IL-6 levels in the CSF as well as cell invasion into the CSF and brain parenchyma (P<0.05). However, the use of thioat-backbone and ammonium as the counterion induced the highest IL-6 levels (7210+/-1696 pg/ml, P<0.05) and the highest cell numbers in the CSF (31.6+/-15.5x10(5)/ml, P<0.05) as well as brain parenchyma (268.1+/-143.2 HIS-48+ cells/mm(2), P<0.01; and 31.3+/-10.7 OX-6+cells/mm(2), P<0.05) compared with the other groups.
Elepfandt
Peter
P
Department of Neurosurgery, Charité Medical School, Humboldt University of Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Rupprecht
Stefan
S
Schöning-Burkhardt
Britta
B
Volk
Hans-Dieter
HD
Woiciechowsky
Christian
C
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D004660:Encephalitis / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000276:immunology; D007260:Infusion Pumps / Q000706:statistics & numerical data; D007276:Injections, Intraventricular / Q000379:methods / Q000706:statistics & numerical data; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015850:Interleukin-6; D020319:Oligodeoxyribonucleotides, Antisense