title: Polyamines induce blood-brain barrier disruption and edema formation in the rat.
abstract: Polyamines (PA) are derived from ornithine by the enzyme ornithine decarboxylase (ODC), which is activated very rapidly as acute and delayed responses to brain ischemia and trauma. Polyamines play a role in the disruption of the blood-brain barrier (BBB) in different pathological states. This study examined the effect of exogenous polyamines, administered intracerebrally (i.c.v.) or intracarotidly on BBB function. Putrescine, spermidine and spermine, given individually, were found to disrupt BBB integrity within 15 min of i.c.v. administration (p = 0.03; p = 0.0013; p = 0.042 vs saline treated rats, respectively). The effect was still evident after 1 h; however, since the saline treated rats also showed increased permeability of Evans blue at this time, there was no statistical difference between polyamines or saline treated rats 1 h post injection. When injected into the carotid artery, rapid increase in BBB permeability was found 1 min after putrescine and spermidine (p < 0.01 vs saline), with a slight decline at 15 min. A slower effect was noticed after spermine administration which reached significance only at 15 min. These results suggest a role for PA as mediators of vasogenic edema formation in the brain soon after brain injuries which induce increased production of these compounds.
authors.affiliation: Department of Pharmacology, Hebrew University, Jerusalem, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Glantz
authors.forename: J L
authors.initials: JL
authors.lastname: Nates
authors.forename: V
authors.initials: V
authors.lastname: Trembovler
authors.forename: R
authors.initials: R
authors.lastname: Bass
authors.forename: E
authors.initials: E
authors.lastname: Shohami
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001929:Brain Edema / Q000145:classification; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011073:Polyamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013046:Specific Gravity
chemical_list: D018696:Neuroprotective Agents; D011073:Polyamines; D013759:Dronabinol; C062018:HU 211