dinoprost and Cerebral-Infarction

Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (aSAH), which is responsible for significant death and disability. The dynamic balance between the production and elimination of reactive oxygen species (ROS) in patients with DCI is suspected be shifted to favor ROS formation. The authors assessed the relationship between F2-isoprostanes (F2-IsoPs), oxidative stress biomarkers, and glucose-6-phosphate dehydrogenase (G6PD), which are responsible for nicotinamide adenine dinucleotide phosphate (NADPH) production for glutathione system function, with post-aSAH DCI.. The authors assessed 45 aSAH patients for F2-IsoP and G6PD concentration using commercial ELISA on days 2, 4, and 6 after aSAH. The authors examined the correlation between plasma F2-IsoP and G6PD concentrations and clinical factors with DCI occurrence and aSAH outcome.. Expectedly, the most important clinical predictors of DCI were Hunt and Hess grade and modified Fisher (mFisher) grade. Plasma F2-IsoP and G6PD concentrations were greater in aSAH patients than the control group (p < 0.01). F2-IsoP concentrations were greater and G6PD concentrations were lower in patients with DCI than those without (p < 0.01). Plasma F2-IsoP and G6PD concentrations on day 2 were correlated with DCI occurrence (p < 0.01). Plasma F2-IsoP concentrations on days 2 and 6 were correlated with outcome at 1 and 12 months (p < 0.01).. Decreased G6PD indirectly informs the reduced antioxidant response, especially for the glutathione system. G6PD concentration was lower in patients with DCI than those without, which may explain the increased F2-IsoP concentrations. mFisher grade, plasma F2-IsoP concentration, and G6PD concentration on day 2 after aSAH, in combination, may serve as predictors of DCI. Further research is necessary to investigate the therapeutic utility of F2-IsoPs and antioxidants in clinical practice.

Topics: Brain Ischemia; Cerebral Infarction; Dinoprost; Glucosephosphate Dehydrogenase; Glutathione; Humans; Prospective Studies; Reactive Oxygen Species; Subarachnoid Hemorrhage

Spontaneous, recurrent spreading depolarizations (SD) are increasingly more appreciated as a pathomechanism behind ischemic brain injuries. Although the prostaglandin F2α - FP receptor signaling pathway has been proposed to contribute to neurodegeneration, it has remained unexplored whether FP receptors are implicated in SD or the coupled cerebral blood flow (CBF) response. We set out here to test the hypothesis that FP receptor blockade may achieve neuroprotection by the inhibition of SD. Global forebrain ischemia/reperfusion was induced in anesthetized rats by the bilateral occlusion and later release of the common carotid arteries. An FP receptor antagonist (AL-8810; 1 mg/bwkg) or its vehicle were administered via the femoral vein 10 min later. Two open craniotomies on the right parietal bone served the elicitation of SD with 1 M KCl, and the acquisition of local field potential. CBF was monitored with laser speckle contrast imaging over the thinned parietal bone. Apoptosis and microglia activation, as well as FP receptor localization were evaluated with immunohistochemistry. The data demonstrate that the antagonism of FP receptors suppressed SD in the ischemic rat cerebral cortex and reduced the duration of recurrent SDs by facilitating repolarization. In parallel, FP receptor antagonism improved perfusion in the ischemic cerebral cortex, and attenuated hypoemic CBF responses associated with SD. Further, FP receptor antagonism appeared to restrain apoptotic cell death related to SD recurrence. In summary, the antagonism of FP receptors (located at the neuro-vascular unit, neurons, astrocytes and microglia) emerges as a promising approach to inhibit the evolution of SDs in cerebral ischemia.

Topics: Animals; Brain Ischemia; Cerebral Cortex; Cerebral Infarction; Cerebrovascular Circulation; Cortical Spreading Depression; Dinoprost; Male; Prosencephalon; Prostaglandins; Rats, Sprague-Dawley; Signal Transduction

Oxygen radicals play a crucial role in brain injury. Grape seed extract is a potent anti-oxidant. Does grape seed extract reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid arteries permanently ligated followed by 2.5 h of hypoxia (8% oxygen). Grape seed extract, 50 mg/kg, or vehicle was administered by i.p. 5 min prior to hypoxia and 4 h after reoxygenation and twice daily for 1 day. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia and by histopathology. Grape seed extract reduced brain weight loss from 20.0+/-4.4% S.E.M. in vehicle pups (n=21) to 3.1+/-1.6% in treated pups (n=20, P<0.01). Grape seed extract improved the histopathologic brain score in cortex, hippocampus and thalamus (P<0.05 versus vehicle). Concentrations of brain 8-isoprostaglandin F2alpha and thiobarbituric acid reacting substances significantly increased due to hypoxic ischemia. Grape seed extract reduced this increase. Treatment with grape seed extract suppresses lipid peroxidation and reduces hypoxic ischemic brain injury in neonatal rat.

Topics: Animals; Animals, Newborn; Body Temperature; Cerebral Infarction; Dinoprost; Dose-Response Relationship, Drug; Functional Laterality; Hypoxia-Ischemia, Brain; Lipid Peroxidation; Plant Extracts; Rats; Rats, Sprague-Dawley; Seeds; Statistics, Nonparametric; Thiobarbituric Acid Reactive Substances; Time Factors; Vitis

Topics: Adult; Alprostadil; Cerebral Infarction; Cerebrovascular Disorders; Dinoprost; Dinoprostone; Humans; Ischemic Attack, Transient; Middle Aged; Platelet Aggregation; Prostaglandins; Prostaglandins E; Prostaglandins F