Poster at 7th International Neurotrauma Symposium, Adelaide, Australia, 12-16 September 2004

Long lasting protective effects induced by the immune modulator PN277 given 24 hours post permanent middle cerebral artery occlusion in rats.

Geffen Y, Ziv Y,* Kipnis Y*, Smirnov I ,Shpilman S, Vertkin I ,Kimron M, Kazanovsky L, Schwartz M*, Yoles E
Proneuron Biotechnologies, Ness –Ziona 74101, Israel    
*Dept. Neurobiology, The Weizmann Institute of Science, Rehovot, 76100, Israel

Stroke is the most common cause of long-term disability in adulthood. In addition to a wide range of motor and sensory deficits, stroke often results in cognitive and behavioral abnormalities. As in other neurodegenerative disorders, the immune response evoked by the injury mediates both degenerative and repair processes. . PN277 is a synthetic copolymer that was shown to have an immune modulation activity which augments the protective immune response. In this study we examined the protective effect of PN277 in the rat model of permanent middle cerebral artery occlusion (MCAO). A single injection of PN277, administered 24 hours post MCAO, significantly improved neurological outcome measured up to 6 weeks post occlusion. Behavioural evaluation using the Morris Water Maze showed significant deficits in spatial learning abilities of the rats as measured 4 weeks post MCAO with no effect of the treatment. However, in the visible platform task the control group displayed significant abnormal behaviour whereas the PN277 treated group behaved similarly to the sham operation group. Administration of PN277 had no effect on infarct volume, but enhanced hippocampus neuron survival and increased proliferation in the sub ventricular zone (SVZ) of the brain, the area that contains neuronal progenitor cells. The SVZ of PN277 treated group also showed increased immunoreactivity against Nestin, an embryonic intermediate filament expressed by neural progenitor cells. PN277 may be used as a unique immune-based therapy that offers long-lasting functional and behavioural recovery, even when given as late as 24 hours after insult.