Influence of Haptoglobin Polymorphism on Stroke in Sickle Cell Disease Patients

This review outlines the current clinical research investigating how the haptoglobin (Hp) genetic polymorphism and stroke occurrence are implicated in sickle cell disease (SCD) pathophysiology. Hp is a blood serum glycoprotein responsible for binding and removing toxic free hemoglobin from the vasculature. The role of Hp in patients with SCD is critical in combating blood toxicity, inflammation, oxidative stress, and even stroke. Ischemic stroke occurs when a blocked vessel decreases oxygen delivery in the blood to cerebral tissue and is commonly associated with SCD. Due to the malformed red blood cells of sickle hemoglobin S, blockage of blood flow is much more prevalent in patients with SCD. This review is the first to evaluate the role of the Hp polymorphism in the incidence of stroke in patients with SCD. Overall, the data compiled in this review suggest that further studies should be conducted to reveal and evaluate potential clinical advancements for gene therapy and Hp infusions.

Effective method of monitoring cerebral tissue oxygen saturation in cardiac surgery patients by combined use of tNIRS-1 and bispectral index

To continuously and noninvasively monitor the cerebral tissue oxygen saturation (StO2) and hemoglobin concentration (gasHb) in cardiac surgery patients, a method combining the use of a cerebral tissue oximeter using near infrared time-resolved spectroscopy (tNIRS-1) and the bispectral index (BIS) was developed in this study. Moreover, the correlation between the estimated hemoglobin concentration (estHb), measured via tNIRS-1, and the hemoglobin concentration (gasHb), analyzed using a blood gas analyzer, were compared. The relationship between the BIS and gasHb was also examined. Through the comparison of BIS and StO2 (r1), and estHb and gasHb (r2), the correlation between the two was clarified with maximum r1 and r2 values of 0.617 and 0.946, respectively. The relationship between BIS and gasHb (r3), showed that there was a favorable correlation with a maximum r3 value of 0.969. There was also a continuous correlation between BIS and StO2 in patients undergoing cardiac surgery. In addition, a strong correlation was found between estHb and gasHb, and between BIS and gasHb. It was therefore concluded that the combined use of BIS and tNIRS-1 is useful to evaluate cerebral hypoxia, allowing for quick response to cerebral hypoxia and reduction of hemoglobin concentration during the operation.

Rapid and Persistent Decrease in Brain Tissue Oxygenation in Ovine Gram-negative Sepsis

The changes in brain perfusion and oxygenation in critical illness, which are thought to contribute to brain dysfunction, are unclear due to the lack of methods to measure these variables. We have developed a technique to chronically measure cerebral tissue perfusion and oxygen tension in unanesthetised sheep. Using this technique, we have determined the changes in cerebral perfusion and PO2 during the development of ovine sepsis. In adult Merino ewes, fibre-optic probes were implanted in the brain, renal cortex and renal medulla to measure tissue perfusion, oxygen tension (PO2) and temperature and flow probes were implanted on the pulmonary and renal arteries. Conscious sheep were infused with live Escherichia coli for 24-hr, which induced hyperdynamic sepsis; mean arterial pressure decreased (85.2±5.6 to 71.5±8.7 mmHg), while cardiac output (4.12±0.70 to 6.15±1.26 L/min) and total peripheral conductance (48.9±8.5 to 86.8±11.5 mL/min/mmHg) increased (n=8, all P<0.001) and arterial PO2 decreased (104±8 to 83±10 mmHg; P<0.01). Cerebral perfusion tended to decrease acutely, although this did not reach significance, but there was a significant and sustained decrease in cerebral tissue PO2 (32.2±10.1 to 18.8±11.7 mmHg) after 3 h and to 22.8±5.2 mmHg after 24-hr of sepsis (P<0.02). Sepsis induced large reductions in both renal medullary perfusion and PO2 but had no effect in the renal cortex. In ovine sepsis, there is an early decrease in cerebral PO2 that is maintained for 24-hours despite minimal changes in cerebral perfusion. Cerebral hypoxia may be one of the factors causing sepsis-induced malaise and lethargy.

Neuroprotective effect of Foeniculum vulgare essential oil in developing Wistar rats exposed to manganese chloride

The present study was carried out in order to evaluate, on the one hand, the modifications induced by manganese chloride according to a neurobehavioral, biochemical and histological approach in developing Wistar rats and, on the other hand, to test the effectiveness of Foeniculum vulgare (fennel) essential oil (FEO) in restoring or not the harmful effects of manganese chloride (MnCl2). The characterization of this essential oil by gas chromatography showed that the major component is E-anethole (34.7907%). The administration of FEO corrected the depressive state, anxiety and locomotor hypoactivity respectively observed in rats exposed to MnCl2, thus, the FEO restored the activity of the various antioxidant enzymes with a clear improvement of the cerebral tissue architecture in intoxicated rats treated with FEO. In conclusion, the FEO has a beneficial effect on the nervous system of rats intoxicated with MnCl2 which justifies the importance of this oil in traditional medicine.

The effect of continuous PEEP administration during surfactant instillation on cerebral hemodynamics in intubated preterm infants: a NIRS study

Objective: There is an ongoing debate about the best and comfortable way to administer surfactant. We hypothesized that uninterrupted respiratory support and continuous PEEP implementation while instilling surfactant via endotracheal tube (ETT) with side port will result in higher regional cerebral tissue oxygenation (rcSO2) and the alterations in cerebral hemodynamics will be minimal. Methods: Preterm infants who required intubation in the delivery room and/or in the first 24 hours of life with gestational age <32 were enrolled. Patients were intubated either via conventional ETT or ETT with side port (Vygon®) with appropriate sizes. Following NICU admission a NIRS probe placed on the forehead and each infant started to monitored with NIRS.In conventional ETT group, patients separated from the ventilator while surfactant was instilled. In ETT with side port group respiratory support was not interrupted during instillation. Heart rate, oxygen saturations, rcSO2, cerebral fractional tissue oxygen extraction (cFTOE) and blood pressures were recorded. Results: A total of 46 infants analyzed. Surfactant was instilled with conventional ETT in 23 and ETT with side port in 23 infants. Birth weights (1037±238 vs 1152±277g) and gestational ages (28±2.3 vs 29±1.6weeks) did not differ between groups. During instillation of surfactant, rcSO2 levels [61.5 (49-90) vs 70 (48-85)] and cFTOE levels 0.28 (0.10-0.44) vs 0.23 (0.03-0.44)] were similar (p=0.58 and 0.82 respectively). Conclusion: Interruption of respiratory support during surfactant instillation did not significantly alter the cerebral tissue oxygenation. These results did not support our hypothesis and should be confirmed with further studies.

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction

Huangqi Chifeng Tang (HQCFT), a traditional Chinese formula of three herbs, has been used to treat cerebral infarction (CI). Saposhnikoviae Radix (SR) was designed as a guiding drug for HQCFT to improve its angiogenic and anti-inflammatory effects. In this study, TTC staining was used to detect the area of CI. H&E staining was used to detect the histopathologic changes in the cerebral tissue. Western blotting was performed to detect the protein expression of NLRP3, caspase 1, IL-1β, IL-6, TNF-α, MMP-9, VEGF, and VEGFR2 in cerebral tissue. Immunohistochemistry was used to detect the protein expression of MMP-9, VEGF, and VEGFR2. The contents of HIF-1α, NLRP3, caspase 1, IL-1β, IL-6, and TNF-α in the serum were determined by ELISA. Our study showed that HQCFT and HQCFT-SR could improve the pathological condition and reduce the infarcted area of the brain tissue in a rat model. In addition, HQCFT and HQCFT-SR significantly decreased the expression levels and serum contents of NLRP3, caspase 1, IL-1β, IL-6, and TNF-α; increased the expression levels of the VEGF and VEGFR2 proteins; and obviously reduced the serum content of HIF-1α. Importantly, the cytokines in brain tissue and serum from the HQCFT group exhibited better efficacy than those from the HQCFT-SR group. HQCFT exerted significant angiogenic and anti-inflammatory effects in rats subjected to middle cerebral artery occlusion (MCAO); these effects can be attributed to the guiding and enhancing effect of SR.

Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus

Aquaporin-4 (AQP4) is the principal water channel in the brain being expressed in astrocytes and ependymal cells. AQP4 plays an important role in cerebrospinal fluid (CSF) homeostasis, and alterations in its expression have been associated with hydrocephalus. AQP4 contributes to the development of hydrocephalus by hypoxia in aged mice, reproducing such principal characteristics of the disease. Here, we explore whether these alterations associated with the hydrocephalic state are permanent or can be reverted by reexposure to normoxia. Alterations such as ventriculomegaly, elevated intracranial pressure, and cognitive deficits were reversed, whereas deficits in CSF outflow and ventricular distensibility were not recovered, remaining impaired even one month after reestablishment of normoxia. Interestingly, in AQP4−/− mice, the impairment in CSF drainage and ventricular distensibility was completely reverted by re-normoxia, indicating that AQP4 has a structural role in the chronification of those alterations. Finally, we show that aged mice subjected to two hypoxic episodes experience permanent ventriculomegaly. These data reveal that repetitive hypoxic events in aged cerebral tissue promote the permanent alterations involved in hydrocephalic pathophysiology, which are dependent on AQP4 expression.