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Background: There is conflicting information about the effect of vitamin C on brain oxygenation during anesthesia. Objectives: The current study was designed and performed to assess the effect of vitamin C infusion and brain oxygenation with cerebral oximetry on improving brain perfusion during general anesthesia in vascular surgery of diabetic patients. Methods: This randomized clinical trial was performed on patients candidates for endarterectomy under general anesthesia and referred to Taleghani Hospital in Tehran, Iran, during 2019 - 2020. Considering inclusion criteria, the patients were divided into placebo and intervention groups. The patients in the placebo group received 500 mL of isotonic saline. In the intervention group, the patients received 1 g of vitamin C diluted in 500 mL of isotonic saline by infusion half an hour before anesthesia induction. Patients’ oxygen levels were continuously measured by a cerebral oximetry sensor. The patients were put in a supine position for 10 minutes before and after anesthesia. At the end of the surgery, the indicators considered in the study were evaluated. Results: No considerable difference was observed between systolic and diastolic blood pressure, heart rate, mean arterial pressure, partial pressure of carbon dioxide, oxygen saturation, regional oxygen saturation, supercritical carbon dioxide, and end-tidal carbon dioxide in total and between the two groups in the three stages before and after anesthesia induction and at the end of surgery (P > 0.05). Additionally, there was no significant difference between blood sugar (BS) levels in the study groups (P > 0.05) but in BS levels at three stages before and after anesthesia induction and at the end of the surgery, with a significant difference (P < 0.05). Conclusions: The amount of perfusion in the two groups and, therefore, in total at the three stages before and after anesthesia induction and at the end of surgery is not different.

Commonly prescribed selective serotonin reuptake inhibitors (SSRIs) inhibit the serotonin transporter to correct a presumed deficit in extracellular serotonin signaling during depression. These agents bring clinical relief to many who take them; however, a significant and growing number of individuals are resistant to SSRIs. There is emerging evidence that inflammation plays a significant role in the clinical variability of SSRIs, though how SSRIs and inflammation intersect with synaptic serotonin modulation remains unknown. In this work, we use fast in vivo serotonin measurement tools to investigate the nexus between serotonin, inflammation, and SSRIs. Upon acute systemic lipopolysaccharide (LPS) administration in male and female mice, we find robust decreases in extracellular serotonin in the mouse hippocampus. We show that these decreased serotonin levels are supported by increased histamine activity (because of inflammation), acting on inhibitory histamine H3 heteroreceptors on serotonin terminals. Importantly, under LPS-induced histamine increase, the ability of escitalopram to augment extracellular serotonin is impaired because of an off-target action of escitalopram to inhibit histamine reuptake. Finally, we show that a functional decrease in histamine synthesis boosts the ability of escitalopram to increase extracellular serotonin levels following LPS. This work reveals a profound effect of inflammation on brain chemistry, specifically the rapidity of inflammation-induced decreased extracellular serotonin, and points the spotlight at a potentially critical player in the pathology of depression, histamine. The serotonin/histamine homeostasis thus, may be a crucial new avenue in improving serotonin-based treatments for depression. SIGNIFICANCE STATEMENT Acute LPS-induced inflammation (1) increases CNS histamine, (2) decreases CNS serotonin (via inhibitory histamine receptors), and (3) prevents a selective serotonin reuptake inhibitor (SSRI) from effectively increasing extracellular serotonin. A targeted depletion of histamine recovers SSRI-induced increases in extracellular hippocampal serotonin.