title: Effects of acute post-treatment with dipyridamole in a rat model of focal cerebral ischemia.
abstract: Dipyridamole (DP) is a platelet inhibitor with known antithrombotic benefits in stroke prevention. In addition to its anti-aggregant properties, recent studies have reported that DP promotes anti-inflammatory, anti-oxidative and neuroprotective effects. We aimed to test whether post-treatment with DP may exert protection after ischemic cerebral injury in the rat. For this purpose, rats were subjected to 120 min or 90 min of middle cerebral artery occlusion (MCAO) followed by 24 or 48 h of reperfusion, respectively. Either DP (100mg/kg) or vehicle was administered i.v. at the onset of reperfusion; rats subjected to 90 min MCAO also received additional doses of DP orally (60 mg/kg) at 24 and 36 h after ischemia. Matrix metalloproteinases, extravasated hemoglobin content and IL-6, MIP-1α and MCP-1 cytokine level were examined in brain tissue by zymography, western blot and multiple ELISA, respectively. DP post-treatment led to a neurological improvement in both models (p < 0.05) and a significant reduction in the infarct volume of rats subjected to 90 min of ischemia, as compared to vehicle group (7.9% vs. 24.4%, p = 0.03). This neuroprotection was accompanied by a modest increase in expression of MMP-9 pro-form and a significant attenuation of MIP-1α levels in the infarcted hemisphere. These results provide support for the development of novel therapies based on DP for acute treatment of stroke. In selected animals, intravenous administration of high dose DP induced an adverse hypotensive effect leading to rapid death. Thus, alternative ways of acute administration must be examined in order to avoid this unfavorable effect.
authors.affiliation: Neurovascular Research Laboratory, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: García-Bonilla
authors.forename: Victoria
authors.initials: V
authors.lastname: Sosti
authors.forename: Mireia
authors.initials: M
authors.lastname: Campos
authors.forename: Anna
authors.initials: A
authors.lastname: Penalba
authors.forename: Cristina
authors.initials: C
authors.lastname: Boada
authors.forename: Mireia
authors.initials: M
authors.lastname: Sumalla
authors.forename: Mar
authors.initials: M
authors.lastname: Hernández-Guillamon
authors.forename: Anna
authors.initials: A
authors.lastname: Rosell
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D018932:Chemokine CCL2 / Q000378:metabolism; D004176:Dipyridamole / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015850:Interleukin-6 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D015424:Reperfusion / Q000009:adverse effects; D013223:Statistics as Topic; D013997:Time Factors
chemical_list: D020346:Aquaporins; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005136:Eye Proteins; D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; C030328:aquaporin 0; D004176:Dipyridamole; D020778:Matrix Metalloproteinase 2