Role of Gd-DOTA in the evaluation and imaging of experimental blood-brain barrier disruption in brain edemas and their improvement after anti-inflammatory drugs treatment.
This study was carried out to evaluate the effect of new anti-inflammatory drugs in the treatment of brain edema in new models. Experimental brain edema was induced in rats by stereotaxic injection of phospholipase A2 into one hemisphere. Concentrations of intravenously injected gadolinium-DOTA in the lesioned hemisphere were three times as high as in normal rat hemisphere. Edema was reduced by treatment with anti-inflammatory drugs such as dexamethasone (P < 0.01) or an experimental benzamide drug (P < 0.02). Magnetic resonance imaging (MRI) was then used to evaluate edema reduction after administration of contrast medium. We observed weighted scans for control lesioned rats, a reduction of signal intensity after dexamethasone and no significant regression after the benzamide drug. For purposes of experimental brain edema research in rats, the MRI technique facilitates detection and evaluation of the anti-inflammatory activity of molecules crossing the blood-brain barrier.
Heuze
I
I
Laboratoire de Pharmacologie et Pharmacocinétique, Faculté de Pharmacie, Nantes, France.
Robert
B
B
Petit
J Y
JY
Welin
L
L
de Kersant-Gilly
A
A
Resche
F
F
Mantoura
J
J
Lajat
Y
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001929:Brain Edema / Q000175:diagnosis* / Q000188:drug therapy*; D003287:Contrast Media; D003907:Dexamethasone / Q000627:therapeutic use; D006571:Heterocyclic Compounds; D008279:Magnetic Resonance Imaging; D008297:Male; D009942:Organometallic Compounds; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001549:Benzamides; D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D003907:Dexamethasone; C058090:N-(4,6-dimethyl-2-pyridinyl)benzamide; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate