Acute treatment with red wine polyphenols protects from ischemia-induced excitotoxicity, energy failure and oxidative stress in rats

Red wine polyphenolic compounds (RWPC) possess numerous neuroprotective activities that may be beneficial for treating cerebral ischemia. To investigate the in vivo effects of an acute treatment with RWPC during stroke, male Wistar rats were subjected to transient ischemia for 90 min and immediately treated with RWPC. The extracellular concentrations of excitatory amino acids, free radical scavengers and energy metabolites during occlusion and reperfusion were monitored using microdialysis. The brain lesions were measured 24 h after reperfusion using immunohistological staining. We found that acute treatment with RWPC significantly reduced the burst of amino acids glutamate, aspartate and taurine in response to ischemia and increased the levels of free radical scavengers ascorbic and uric acids during occlusion or at early reperfusion, respectively. The concentration of glucose was improved during occlusion whereas the level of lactate strongly decreased during reperfusion in RWPC treated animals, suggesting an increased use of this substrate by surviving neurons. RWPC also significantly improved blood flow during reperfusion and brain tissue preservation as observed 24 h after MCAO in treated animals. These findings strongly suggest that RWPC are agents able to fight against the excitotoxic, oxidative pathways and metabolic dysfunction induced by cerebral ischemia

Chronic Treatment with Red Wine Polyphenol Compounds Mediates Neuroprotection in a Rat Model of Ischemic Cerebral Stroke

In this study, we investigated the in vivo effects of red wine polyphenol compounds (RWPC) in rats that were submitted to middle cerebral occlusion as an experimental model of stroke. Male Wistar rats were given RWPC [30 mg/(kg · d) dissolved in drinking water] or water for 1 wk before being subjected to transient middle cerebral artery occlusion followed by reperfusion. Sham-operated rats were subjected to transient occlusion in which the filament was not completely introduced. The release of amino acids and energy metabolites were monitored by intracerebral microdialysis. The volume of the ischemic lesion was assessed 24 h after reperfusion. Proteomic analysis of brain tissue was performed to study the effects of ischemia and RWPC on specific protein expression. Treatment with RWPC completely prevented the burst of excitatory amino acids that occurred in response to ischemia in untreated rats and significantly reduced brain infarct volumes. Rats chronically treated with RWPC, however, had lower basal concentrations of energy metabolites, including glucose and lactate in the brain parenchyma, compared with untreated rats. Chronic RWPC treatment significantly enhanced the residual cerebral blood flow during occlusion and reperfusion in rats subjected to transient occlusion compared with untreated rats. This effect resulted from arterial vasodilatation, as the internal diameters of several arteries were significantly enlarged after RWPC treatment. Proteomic studies revealed the modulation by RWPC of the expression of proteins involved in the maintenance of neuronal caliber and axon formation, in the protection against oxidative stress, and in energy metabolism. These findings provide an experimental basis for the beneficial effects of RWPC on the neurovascular unit during stroke

Cortical brain microdialysis and temperature monitoring during hypothermic circulatory arrest in humans

OBJECTIVES—Critical vascular surgery of the brain or the heart occasionally requires total cessation of the circulatory system. Profound hypothermia is used to protect the brain from ischaemic injury. This study explores the use of microdialysis to measure metabolic indices of ischaemia: glutamate, lactate, and pH, and cerebral temperature during profound hypothermia and circulatory arrest.
METHODS—Effluent from a microdialysis catheter placed in the cerebral cortex of three patients undergoing complete circulatory arrest was continuously sampled. Samples were pooled over 10 minute periods and glutamate and lactate concentrations were measured postoperatively. Brain temperature and pH were measured on line intraoperatively. Electroencephalography and monitoring of somatosensory evoked potentials and brainstem auditory evoked potentials were simultaneously carried out.
RESULTS—Patient 1 had normal glutamate and lactate. PH was 6.75 to 6.85 and increased to 6.9 after warming ensued. Patient 2 had raised glutamate and lactate during most measurements. The glutamate concentrations peaked at 305 µM/l at the start of the measurements and fell below 20 µM/l after warming. The lactate concentrations peaked at 680 µM/l before cooling, rose to 1040 µM/l during the cooling process, decreased to 212 µM/l during circulatory arrest, and rose again to 620 µM/l after warming. The pH started at 7.06and continued a downward course until stabilising at a pH of 6.5after circulatory arrest. Patient 3 had a transient, mild increase in glutamate and lactate during the cooling and warming period. pH was stable throughout.
CONCLUSION—Microdialysis combined with temperature and pH measurements of the cerebral cortex promises to be an important tool in detecting cerebral ischaemia. Further studies are needed to validate our findings and test the feasibility of modifying ischaemic changes.


Microdialytical monitoring of uric and ascorbic acids in the brains of patients after severe brain injury and during neurovascular surgery

OBJECTIVES—Microdialysis has been extensively used to monitor brain metabolism in the extracellular fluid of patients with severe head injury, to detect the onset of secondary ischaemic damage. The aim was to investigate whether concentrations of uric and ascorbic acids were altered in such patients. Both these compounds play a part in free radical metabolism, which is accelerated after ischaemia and brain injury.
METHODS—Patients with aneurysm or bypass operations were monitored intraoperatively to assess concentrations in minimally disturbed tissue. Afterwards, 13 patients with severe head trauma were monitored for up to 13 days in the intensive care unit.
RESULTS—Intraoperatively, concentrations of both ascorbic and uric acids were significantly higher in the bypass group than in patients with aneurysm, which might be attributed to chronic ischaemic conditions caused by the unilateral occlusion of the carotid artery. In the patients with trauma, mean values of uric acid, varying between 6 µM and 180 µM, did not correlate with type of injury (contusion or diffuse) or duration of monitoring time. Patients who died had significantly higher concentrations of uric acid than those with a good outcome. Ascorbic acid could be detected only intermittently, probably due to technical problems. Concentrations of these two compounds could not be correlated with clinical findings during the course of monitoring.
CONCLUSIONS—Although uric and ascorbic acids are influenced by ischaemic conditions—for example, in bypass patients, neither compound is suitable for monitoring for free radical activity after severe head injury. Patients with a bad outcome tended to have higher concentrations of uric acid.