c-Jun N-Terminal Kinase Pathway Inhibition in Intracerebral Hemorrhage (original) (raw)

Cerebrovascular Diseases, 2010

Abstract

Background: Inhibition of the c-Jun N-terminal kinase (JNK) pathway by the TAT-coupled peptide XG-102 (formerly D- JNKI1) induces strong neuroprotection in ischemic stroke in rodents. We investigated the effect of JNK inhibition in intracerebral hemorrhage (ICH). Methods: Three hours after induction of ICH by intrastriatal collagenase injection in mice, the animals received an intravenous injection of 100 µg/kg of XG-102. The neurological outcome was assessed daily and the mice were sacrificed at 6 h, 1, 2 or 5 days after ICH. Results: XG-102 administration significantly improved the neurological outcome at 1 day (p < 0.01). The lesion volume was significantly decreased after 2 days (29 ± 11 vs. 39 ± 5 mm3 in vehicle-treated animals, p < 0.05). There was also a decreased hemispheric swelling (14 ± 13 vs. 26 ± 9% in vehicle-treated animals, p < 0.05) correlating with increased aquaporin 4 expression. Conclusions: XG-102 attenuates cerebral edema in ICH and functional impairm...

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