Figure 4.

MgSO₄ preconditioning prevents succinate and GABA accumulation as well as high-energy phosphate depletion in the brain after HI.(a) Principal component analysis (OPLS-DA) of the metabolomic analysis of cortex samples (ipsi- and contralateral) collected 3 h after i.p. injection with vehicle (n = 9) as shown in blue or MgSO₄ (n = 6) shown in green. (b) Metabolic trace plots of succinate levels in cerebral cortex after 60 min of HI (red) in samples from rats injected with vehicle (n = 9) or MgSO₄ (n = 6) 24 h prior to HI in contra- and ipsilateral hemisphere and in animals exposed to treatment without HI 3 h or 24 h prior to sampling. (c) Cerebro-cortical metabolites 3 h and 24 h after administration of MgSO₄ or vehicle, and 24 h of MgSO₄ or vehicle + 60 min of HI (60′). There was an accumulation of succinate (p < 0.05) and GABA (p < 0.001) after 60 min of HI in the vehicle group but not in MgSO₄-treated group. Depletion of phosphocreatine (p < 0.0002) and ADP/ATP (p < 0.02) was attenuated during HI in the MgSO₄ group compared to vehicle-treated group. The lactate concentration increased to the same extent in MgSO₄ pre-treated animals (p < 0.0001) as in vehicle (p < 0.0001) after HI and glucose concentrations decreased in the cerebral cortex following HI in both groups (n = 6–10/condition), (one-way ANOVA with Tukey's multiple comparisons test).