Alterations in blood-brain barrier function and brain pathology by morphine in the rat. Neuroprotective effects of antioxidant H-290/51.
The possibility that stress associated with morphine administration or withdrawal will influence the blood-brain barrier (BBB) dysfunction, brain edema formation and brain pathology was examined in a rat model. Repeated daily administration of morphine (10 mg/kg, i.p.) resulted in drug dependence in rats on the 6th day and onwards. The BBB permeability to Evans blue albumin (EBA) and radioiodine ([131])Iodine did not alter during morphine dependence up to the 12th day. On the other hand, spontaneous withdrawal of morphine on day 1 resulted in profound stress symptoms and breakdown of the BBB to protein tracers in several brain regions. This increase in BBB to protein tracers was most pronounced on the 2nd day of morphine withdrawal. These rats also exhibited marked brain edema and abnormal neuronal and glial cell responses. Pretreatment with an antioxidant H-290/51 markedly attenuated the BBB dysfunction, brain edema formation and brain pathology during morphine withdrawal phases. These observations suggest that psychostimulants and associated oxidative stress are capable to induce brain pathology through modifying the BBB function.
Sharma
Hari Shanker
HS
Laboratory of Cerebrovascular Research, Department of Surgical Science, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala, Sweden. Sharma@surgsci.uu.se
Sjöquist
Per-Ove
PO
Ali
Syed F
SF
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000150:complications / Q000473:pathology*; D009294:Narcotics / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; C088233:H290-51; D007211:Indoles; D009294:Narcotics; D018696:Neuroprotective Agents; D009020:Morphine