Ninety-six adult Sprague-Dawley rats were used in this study. The animals surviving from CPR were sacrificed 0, 3, 6 and 24 h following CPR and the protein levels of HIF-1α and VEGF in the hippocampus were determined. VEGFR-2, Caspase-3 and NF-kB were also examined in control rats, and rats that survived for 24 h after CPR and were given with DMOG/ML228. Moreover, neurological functions were estimated in control rats and rats with DMOG/ML228.
Our results show that HIF-1α and VEGF were significantly increased in the hippocampus 3–24 h after CA. Significant increases in VEGFR-2, Caspase-3 and NF-κB were observed in the hippocampus 24 h after CA (P < 0.05 vs. control group). Nonetheless, DMOG and ML228 significantly augmented VEGFR-2, attenuated Caspase-3 and neuronal apoptosis, and improved neurological Severity Score and tissue edema (P < 0.05 vs. saline group), without affecting expression of NF-κB.
Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that HIF-1α plays an important role in regulating expression of VEGFR-2 and Caspase-3 as well as improving neurological functions and neuronal edema. The subsequent induction of HIF-1α and its target signal pathways is likely a part of the intrinsic neuroprotective effects aimed at attenuating damage as a result of global cerebral ischemia. Thus, targeting one or more of these signaling molecules has clinical implications for treatment and management of CA-evoked global cerebral ischemia often observed in clinics.