Asphyxial cardiac arrest (ACA)-induced ischemia results in acute and delayed neuronal cell death. The early reperfusion phase is critical for the outcome. Intervention strategies directed to this period are promising to reduce ACA/resuscitation-dependent impairments. This study focused on the evaluation of the protective potential of an extract from Gynostemma pentaphyllum (GP), a plant used in traditional medicine with antioxidative, glucose lowering and neuroprotective activities, in an ACA rat model. We tested the following parameters: i) Basic systemic parameters such as pCO2 and blood glucose value within the first 30 min post-ACA; ii) mitochondrial response by determining activities of citrate synthase, respiratory chain complexes I + III and II + III, and the composition of cardiolipin 6 and 24 h post-ACA; iii) neuronal vitality of the CA1 hippocampal region by immunohistochemistry 24 h and 7 days post-ACA; and iv) cognitive function by a novel object recognition test 7 days post-ACA. GP, administered after reaching spontaneous circulation, counteracted the following: i) ACA-mediated increases in arterial CO2 tension and blood glucose values; ii) transient increase in the activity of the respiratory chain complexes II + III; iii) elevation in cardiolipin content; iv) hippocampal CA1 neurodegeneration, and v) loss of normal novelty-object seeking. The protective effects of GP were accompanied by side effects of the vehicle DMSO, such as the stimulation of citrate synthase activity in control animals, inhibition of cardiolipin synthesis in ACA animals and complex II + III activity in both control and ACA animals. The results emphasize the importance of the early post-resuscitation phase for the neurological outcome after ACA/resuscitation, and demonstrated the power of GP substitution as neuroprotective intervention. Moreover, the results underline the need of a careful handling of the popular vehicle DMSO.
Keywords: asphyxial cardiac arrest; cardiolipin; dimethyl sulfoxide; hippocampus; mitochondria; object recognition.