This is in accordance with our results, as expression of caspase 3 and 9 was augmented in both the cytosolic hippocampus and mitochondrial fractions in the Hx group. Other experimental studies have shown similar results. The absence of changes in the Bax/Bcl-x ratio and in the activity of caspase 3 and 9 in the hemodiluted groups are interesting because, to our knowledge, no other study has evaluated the presence of these apoptotic markers at 10 and 15% hematocrit levels in cerebral tissue. However, it cannot be ruled out that more intense anemic conditions for a longer period of time could result in apoptosis and lead to alterations in Bcl family protein expression. Our results contradict other experimental studies focused on hemodilution that found increased cerebral expression of hypoxia to induce markers such as HIF-1a and neuronal nitric oxide synthase. However, these studies have not shown the association between these markers and neuronal injury. Other studies have also demonstrated that hemodilution can exacerbate neurological injury after CPB with or without circulatory arrest, focal cerebral ischemia and trauma. Nevertheless, these results demonstrate the sum effect of hemodilution and CBP, not the effect of isolated acute anemia. Bucetin Furthermore, our animals were maintained within a normal temperature range, thus avoiding cerebral protection by hypothermia. Our results also showed that while hypoxia significantly increased mitochondrial DNA fragmentation in the Hx group, there was no increase with hemodilution to Heparin sodium target hematocrits of 10 or 15%. The apoptotic nuclear DNA fragmentation process associated with cerebral hypoxia is initiated by activation of nuclear Ca2+ influx mechanisms and increases transcription of a number of genes, including the apoptotic genes of the Bcl-2 family responsible for programmed cell death. Proapoptotic proteins initiate apoptosis by activating a caspase system cascade that leads to cleavage of numerous intracellular proteins responsible for the maintenance of cell structure and results in chromosomal DNA cleavage and disruption of cell nuclei.