Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity.
Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we show in a longitudinal magnetic resonance imaging study that Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the main active compound in marijuana, reduces neuronal injury in neonatal rats injected intracerebrally with the Na(+)/K(+)-ATPase inhibitor ouabain to elicit excitotoxicity. In the acute phase Delta(9)-THC reduced the volume of cytotoxic edema by 22%. After 7 d, 36% less neuronal damage was observed in treated rats compared with control animals. Coadministration of the CB(1) cannabinoid receptor antagonist SR141716 prevented the neuroprotective actions of Delta(9)-THC, indicating that Delta(9)-THC afforded protection to neurons via the CB(1) receptor. In Delta(9)-THC-treated rats the volume of astrogliotic tissue was 36% smaller. The CB(1) receptor antagonist did not block this effect. These results provide evidence that the cannabinoid system can serve to protect the brain against neurodegeneration.
van der Stelt
M
M
Department of Bio-Organic Chemistry, Bijvoet Center for Biomolecular Research, 3584 CH, Utrecht University, Utrecht, The Netherlands.
Veldhuis
W B
WB
Bär
P R
PR
Veldink
G A
GA
Vliegenthart
J F
JF
Nicolay
K
K
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D002188:Cannabis; D002908:Chronic Disease; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008845:Microinjections; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010042:Ouabain / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014867:Water / Q000378:metabolism
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014867:Water; D010042:Ouabain; D013759:Dronabinol; D000254:Sodium-Potassium-Exchanging ATPase