Copolymer-1 (Cop-1) improves neurological recovery after middle cerebral artery occlusion in rats.
The damage in ischemic stroke is caused by two events: (i) the ischemic phenomenon by itself; (ii) the self-destructive mechanisms developed as a consequence of ischemia. The inflammatory response is one of these destructive phenomena that accompanies and exacerbates the developing injury. Since it has been suggested that immune cells participate in neuroprotective and restorative processes, modulation rather than elimination of this inflammatory response could be a strategy to improve the neurological outcome. The immune modulator copolymer-1 (Cop-1), a synthetic basic random copolymer of amino acids, is a potent inducer of Th2 regulatory cells which, aside from exerting modulatory actions, is capable of releasing neurotrophic factors. There is evidence that Cop-1-specific T cells exert neuroprotective and even restorative effects in diverse neurodegenerative diseases. In order to test the ability of Cop-1 to prevent ischemic injury in a model of transient middle cerebral artery (MCA) occlusion, two groups of rats were treated either with Cop-1 or with saline solution (SS). Seven days after occlusion, Cop-1 treated rats presented a significant improvement in neurological function compared to SS-treated animals (1.2+/-0.4 and 2.8+/-0.5 mean+/-S.D., respectively; p=0.008). Histological findings showed that the percentage of infarct volume was smaller in Cop-1 treated rats (4.8+/-1.5), in comparison with those receiving SS (32.2+/-8.6; p=0.004). Cop-1 constitutes a promising therapy for stroke; thereby, the enforcement of further experimental investigation is encouraged in order to be able to formulate the best strategy.
Ibarra
Antonio
A
Unidad de Investigación Médica en Enfermedades Neurológicas, HE, CMN Siglo XXI, IMSS, Av. Cuauhtemoc No. 330, Col. Doctores, C.P. 06720, México, D.F., Mexico. iantonio65@yahoo.com
Avendaño
Héctor
H
Cruz
Yolanda
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D000068717:Glatiramer Acetate; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007155:Immunologic Factors; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D010455:Peptides; D000068717:Glatiramer Acetate