title: The neurovascular unit and combination treatment strategies for stroke.
abstract: Tissue plasminogen activator (tPA) administered within 4.5h of symptom onset restores cerebral blood flow (CBF) and promotes neurological recovery of stroke patients. However, the narrow therapeutic time window and the risk of intracerebral hemorrhage after tPA treatment pose major hurdles to its clinical usage. In light of the failures of neuroprotective therapies in clinical trials, emerging concepts suggest that neuroprotection alone without restoration of tissue perfusion and vascular integrity may not be adequate for treatment of acute stroke. Here we review evidence of the use of adjuvant pharmacological agents to extend the therapeutic window for tPA via targeting the neurovascular unit and the underlying mechanisms of the combination therapy in experimental stroke.
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. lzhang@neuro.hfh.edu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002543:Cerebral Hemorrhage / Q000209:etiology; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008911:Minocycline / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001897:Boronic Acids; D005343:Fibrinolytic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011719:Pyrazines; D004921:Erythropoietin; D000069286:Bortezomib; D010959:Tissue Plasminogen Activator; D008911:Minocycline