AIM: Both hyperbaric oxygenation (HBO) and inhibition of the c-Jun N-terminal kinases (JNKs) by the peptide inhibitor XG-102 (D-JNKI-1) are efficient protective strategies against ischaemia-induced neurodegeneration. The present study investigated whether the combination of HBO and JNK inhibitor, XG-102, provides additive neuroprotection against cerebral ischaemia. METHODS: Rat middle cerebral artery was occluded (MCAO) for 90 min. XG-102 [2 mg/kg, intraperitoneally] or HBO (3 ATA, 60 min) was applied 3 h after the onset of MCAO. For the combination treatment, HBO was started 10 min after the injection of XG-102. Twenty-four hours after MCAO, the infarct area, the neurological score and the immunohistochemistry staining in brain slices for cleaved-PARP, transferase-mediated biotinylated UTP nick end labelling, c-Jun and phosphorylated (activated) c-Jun were observed. RESULTS: XG-102 or HBO alone reduced the total infarct area by 43% and 63%, respectively. The combination diminished total infarct area by 78%, improved the neurological function and reduced brain oedema. Co-application of HBO and XG-102 also significantly reduced the cleavage of PARP, by 96% and 91% in cortical penumbra and ischaemic core, respectively. Moreover, cotreatment significantly attenuated the number of cells labelled with transferase-mediated biotinylated UTP nick end labelling and phosphorylated c-Jun. CONCLUSION: Our study demonstrates that HBO reinforces the efficiency of neuroprotective drugs such as XG-102 and vice versa. Both treatments, physical HBO and pharmacological XG-102, are already in phase I/II studies and promising strategies for clinical use.
AIM: Both hyperbaric oxygenation (HBO) and inhibition of the c-Jun N-terminal kinases (JNKs) by the peptide inhibitor XG-102 (D-JNKI-1) are efficient protective strategies against ischaemia-induced neurodegeneration. The present study investigated whether the combination of HBO and JNK inhibitor, XG-102, provides additive neuroprotection against cerebral ischaemia. METHODS:Rat middle cerebral artery was occluded (MCAO) for 90 min. XG-102 [2 mg/kg, intraperitoneally] or HBO (3 ATA, 60 min) was applied 3 h after the onset of MCAO. For the combination treatment, HBO was started 10 min after the injection of XG-102. Twenty-four hours after MCAO, the infarct area, the neurological score and the immunohistochemistry staining in brain slices for cleaved-PARP, transferase-mediated biotinylated UTP nick end labelling, c-Jun and phosphorylated (activated) c-Jun were observed. RESULTS:XG-102 or HBO alone reduced the total infarct area by 43% and 63%, respectively. The combination diminished total infarct area by 78%, improved the neurological function and reduced brain oedema. Co-application of HBO and XG-102 also significantly reduced the cleavage of PARP, by 96% and 91% in cortical penumbra and ischaemic core, respectively. Moreover, cotreatment significantly attenuated the number of cells labelled with transferase-mediated biotinylated UTP nick end labelling and phosphorylated c-Jun. CONCLUSION: Our study demonstrates that HBO reinforces the efficiency of neuroprotective drugs such as XG-102 and vice versa. Both treatments, physical HBO and pharmacological XG-102, are already in phase I/II studies and promising strategies for clinical use.
Authors: Jun Mu; Robert P Ostrowski; Yoshiteru Soejima; William B Rolland; Paul R Krafft; Jiping Tang; John H Zhang Journal: Neurobiol Dis Date: 2012-11-10 Impact factor: 5.996
Authors: Sabrina Marozin; Jennifer Altomonte; Sibylle Apfel; Phat X Dinh; Enrico N De Toni; Antonia Rizzani; Andreas Nüssler; Nobuyuki Kato; Roland M Schmid; Asit K Pattnaik; Oliver Ebert Journal: J Virol Date: 2012-02-15 Impact factor: 5.103
Authors: William R Gow; Kym Campbell; Amanda J Meade; Paul M Watt; Nadia Milech; Neville W Knuckey; Bruno P Meloni Journal: J Cereb Blood Flow Metab Date: 2011-10-05 Impact factor: 6.200