Biochemistry

  • Real-time tracking of brain oxygen gradients and blood flow during functional activation

    Significance

    Cerebral metabolic rate of oxygen (CMRO2) consumption is a key physiological variable that characterizes brain metabolism in a steady state and during functional activation.

    Aim

    We aim to develop a minimally invasive optical technique for real-time measurement of CMRO2 concurrently with cerebral blood flow (CBF).

    Approach

    We used a pair of macromolecular phosphorescent probes with nonoverlapping optical spectra, which were localized in the intra- and extravascular compartments of the brain tissue, thus providing a readout of oxygen gradients between these two compartments. In parallel, we measured CBF using laser speckle contrast imaging.

    Results

    The method enables computation and tracking of CMRO2 during functional activation with high temporal resolution (∼7 Hz). In contrast to other approaches, our assessment of CMRO2 does not require measurements of CBF or hemoglobin oxygen saturation.

    Conclusions

    The independent records of intravascular and extravascular partial pressures of oxygen, CBF, and CMRO2 provide information about the physiological events that accompany neuronal activation, creating opportunities for dynamic quantification of brain metabolism.

  • Elevated Serum Cortisol Levels in Patients with Focal Epilepsy, Depression, and Comorbid Epilepsy and Depression

    Background: The hypothalamic-pituitary-adrenal (HPA) axis, inflammatory processes and neurotrophic factor systems are involved in pathogenesis of both epilepsy and depressive disorders. The study aimed to explore these systems in patients with focal epilepsy (PWE, n = 76), epilepsy and comorbid depression (PWCED n = 48), and major depressive disorder (PWMDD, n = 62) compared with healthy controls (HC, n = 78). Methods: Parameters of the HPA axis, neurotrophic factors, and TNF-α were measured in blood serum along with the hemogram. Results: Serum cortisol level was augmented in PWE, PWCED, and PWMDD compared with HC and was higher in PWMDD than in PWE. Serum cortisol negatively correlated with Mini–Mental State Examination (MMSE) score in PWE, and positively with depression inventory–II (BDI-II) score in PWMDD. Only PWMDD demonstrated elevated plasma ACTH. Serum TNF-α, lymphocytes, and eosinophils were augmented in PWMDD; monocytes elevated in PWE and PWCED, while neutrophils were reduced in PWE and PWMDD. Serum BDNF was decreased in PWE and PWCED, CNTF was elevated in all groups of patients. In PWE, none of above indices depended on epilepsy etiology. Conclusions: The results confirm the involvement of HPA axis and inflammatory processes in pathogenesis of epilepsy and depression and provide new insights in mechanisms of epilepsy and depression comorbidity.