Combined Preconditioning Reduces the Negative Influence of Cerebral Ischemia on the Morphofunctional Condition of CNS.

We studied the influence of combined preconditioning (compound pQ-4 and moderate hypoxia) on morphometrical parameters of neuronal populations in hippocampal fields CA1 and CA3 in rats after bilateral ligation of the common carotid artery. Preconditioning produced a neuroprotective effect, improved survival of pyramidal neurons in the early and delayed periods of modeled ischemia, prevented the formation of necrotic and apoptotic neurons and hyperactivation of microglia, and protected endotheliocytes. The positive influence of preconditioning factors on the morphometric parameters of the brain under ischemic conditions agrees with the results of behavioral tests (open field and elevated plus maze) that demonstrated increased locomotor activity and exploratory behavior of animals.

[Erythropoietin and vascular endothelial growth factor level in normoxia and in cerebral ischemia under pharmacological and hypoxic preconditioning].

The level of erythropoietin (EPO) and vascular endothelial growth factor (VEGF-A) was investigated in blood serum and brain of Wistar rats by the enzyme immunoassay with specific rat antibodies. These growth factors are actively studied as biomarkers of ischemia or cytoprotection, as well as targets for agents initiating preconditioning (PreC). Pharmacological (amtizol administration), hypoxic (hypobaric hypoxia), and combined PreC (amtizol+hypobaric hypoxia) were used as neuroprotective approaches in this experimental work.

Signal Mechanism of the Protective Effect of Combined Preconditioning by Amtizole and Moderate Hypoxia.

The content of regulatory proteins involved in adaptation to hypoxia and ischemia was studied in brain rat homogenate under conditions of normoxia and after bilateral ligation of the common carotid arteries. Preconditioning with amtizole in combination with moderate hypoxia increased the levels of HIF-1α, erythropoietin, vascular endothelial growth factor under conditions of normoxia. During experimental ischemia, combined preconditioning led to stabilization of the content of these regulatory proteins at the level of intact control and to a decrease in glycogen synthase-3β kinase activity.

Neuroprotective Effect of Antioxidants and Moderate Hypoxia as Combined Preconditioning in Cerebral Ischemia.

We studied combined effect of moderate hypoxia and compounds pQ-4, pQ-915, pQ-1032, and pQ-1104 on neurological deficit and survival of rats after bilateral ligation of common carotid arteries. Preconditioning including moderate hypoxia and treatment with compound pQ-4 produced a neuroprotective effect and increased animal survival during the early (by 51%) and late (by 33.5%) periods of modeled ischemia and reduced neurological deficit (by 50% and 41%, respectively).

[INFLUENCE OF COMBINED PHARMACOLOGICAL AND HYPOXIC PRECONDITIONING ON ANIMAL SURVIVAL AND FUNCTIONAL ACTIVITY OF CNS DURING MODEL CEREBRAL ISCHEMIA.].

The combined action of amthizole administration and hypoxia conditions on the survival of rats and the functional state of the central nervous system has been studied on a model of bilateral common carotid artery occlusion. It is established that this combined preconditioning produces cerebroprotective action, increases animal survival after surgery (estimated 72 h upon the onset of ischemia) by 38% (p = 0.029) in early and by 29% (p = 0.