The Role of P2Y6 Receptors in the Mechanisms of the Neuroprotective Effect of Citicoline.

Spontaneous bioelectrical activity of the brain and the duration of gasping were recorded in mice during modeling of global strangulation ischemia of the brain against the background of preventive administration of citicoline. The maximum neuroprotective effect of citicoline was observed when it was administered 60 min before the simulation of ischemia and was completely prevented by preliminary administration of a selective P2Y6 receptor antagonist MRS2578. The obtained experimental data attest to the leading role of receptor mechanisms in the implementation of neuroprotective activity of citicoline.

Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord.

Changes in functional and metabolic activities of the brain were evaluated by EEG and positron-emission/computer tomography with 18F-fluorodeoxyglucose in patients with neuropathic pain syndrome previous to and 3 months after implantation of a system for chronic epidural spinal cord stimulation. In most cases, the use of a nerve stimulator was followed by alleviation of neuropathic pain and partial normalization of functional and metabolic activities of brain structures responsible for pain perception, emotiogenic, behavioral, and autonomic responses.

Effect of cyclopentyladenosine on lipid peroxidation during focal cerebral ischemia.

The antioxidant effect of an adenosine A1 receptor agonist cyclopentyladenosine was studied on the model of focal cerebral ischemia. Ischemic injury of the brain was accompanied by changes in LPO processes (in the blood and brain tissue) and failure of some factors for antioxidant protection (peroxidase and catalase) that inactivate reactive metabolites. Changes in the ratio between LPO and antioxidant protection were less pronounced after treatment with cyclopentyladenosine.

[Anticonvulsant and neuroprotective effects of cyclopentyladenosine on the model of convulsive status in rats].

The neuroprotective and anticonvulsant effects of cyclopentyladenosine (CPA) have been studied on a new experimental model of the convulsive status in rats aged 3-4 months and 10 days. The convulsive status was modeled by intracerebroventricular injection of ferakril (water-soluble polymer of polyacrylic acid) solution. It is established that prophylactic administration of CPA results in a relatively lower degree of neurological deficit, both in the acute phase and on the next day, compared to the untreated control. Considering that adenosine receptor agonists are analogs of the natural metabolites that have minimal side effects and expressed neuroprotective properties, the use of agents of this group is perspective for both prevention and treatment of seizure conditions in neurology and neurosurgery.

[Effect of cyclopentyladenosine on the orientation, exploratory, and emotional behavior of rats with model brain injury].

Effects of a local compression brain injury and the preventive application of cyclopentyladenosine (CPA) on the behavior of rats in the open field test was investigated. It is established that the local injury of a parietal cortex causes intensification of the orientation--research behavior and an increase in the emotional stress in rats. A protective action of CPA was manifested by a decrease in the expressiveness and duration of disturbances in the emotional and orientation--research behavior of animals in the open field test.

[Efficiency of neuroendoscopic operations in achieving shunt independency in hydrocephalus with liquor-shunting system dysfunction].

OBJECTIVE: to evaluate the efficiency of endoscopic treatments in achieving shunt independency in patients with hydrocephalus and shunt dysfunction. SUBJECTS AND METHODS: endoscopic treatment was performed in 28 patients (15 males and 13 females) aged 7.0 +/- 1.2 years (0.5-24 years) with hydrocephalus and CSF shunt dysfunction. The interval between the first shunt implantation and endoscopic surgery (the time of shunt dependency) was 43.4 +/- 7.8 months (5-180 months). All operations were made using the universal Gaab neuroendoscopic system (Karl Storz GmbH and Co., Germany). The follow-up lasted 49.4 +/- 6.9 months (6-120 months). RESULTS: All the patients were successfully operated on, without intraoperative complications and deaths being observed. Surgical interventions were as follows: endoscopic ventriculocisternostomy (n=23), endoscopic aqueductoplasty (n=1), and endoscopic cystoventriculocistemrnostomy (n=4). In 24 of the 28 patients, the symptoms of intracranial hypertension regressed completely. CSF shunt reimplantation was required in 3 cases and prolonged external drainage in 1 case of existing ventriculitis. It should be noted that 24 of the 28 patients became shunt-independent; a shunt was removed in 13.

[The topographic anatomy of the interpeduncular cistern and endoscopic ventriculocisternostomy in the region of the bottom of the third ventricle].

The interpeduncular cistern was microanatomically studied on 14 anatomic specimens of the brain. It was divided into 2 parts: superficial (free) and deep (vascular). The upper interpeduncular cistern wall was divided into hypothalamic and mesencephalic parts. The interpeduncular cistern is connected with the ambient, pretontine, carotid, cerebellopontine, oculomotor, and peduncular cisterns. It is a composite space-occupying, structural formation. Liliequist's membrane is the basic membranous component of a cistern. The proposed division makes it possible to study different parts of the interpeduncular cistern qualitatively and quantitatively and to define clear topographic and anatomic criteria as a guideline in this field.

[Protective effect of A-agonists in a minimum invasive model of spinal cord ischemia in rats]. / Zashchitnoe deistvie A-agonistov na maloinvazivnoi modeli ishemii spinnigo mozga u krys.

The neuroprotective properties of N6-cyclohexyladenosine (CHA) and N6-cyclopentyladenosine (CPA), adenosine receptor agonists (A-agonists), were studied on a model of spinal cord ischemia (SCI) in rats (most closely reproducing the analogous clinical pathological process in humans). The SCI model was induced by intravasal occlusion of the abdominal aorta and its branches. CHA and CPA were introduced by intracerebroventricular injections in a dose of 25 micrograms/kg, 60 min before SCI induction. The protective effect was judged by comparing the patterns of neurological and histopathological disturbances in the untreated control (ischemia) and on the CHA or CPA background. The A-agonist CPA produced a pronounced, statistically reliable neuroprotector effect on the minimum invasive SCI model studied. CHA is also a statistically reliable but less effective neuroprotector. The A-agonists may have good prospects in clinics.

Changes in the steady-state potential in rats with focal cerebral ischemia receiving cyclopentyladenosine.

Brain function and neuroprotective activity of cyclopentyladenosine in rats with focal cerebral ischemia were evaluated by recording the steady-state potential. Cerebral ischemia was modeled by intravasal occlusion of the left internal carotid and middle cerebral arteries and bilateral occlusion of the common carotid arteries. Recording of the steady-state brain potential during experimental ischemia allowed identifying the development of ischemic depolarization by a negative potential shift. Changes in the steady-state potential after cyclopentyladenosine administration reflected delayed development of ischemic depolarization in the nervous tissue. Cyclopentyladenosine holds much promise for the protection of nerve cells from ischemic injury.

New minimally invasive model of spinal cord ischemia in rats.

We developed a new minimally invasive model of spinal cord ischemia in rats: intravascular occlusion of the abdominal aorta and its branches. This model can be used on small laboratory animals and allows qualitatively and quantitatively evaluating the morphofunctional state of the nervous system during spinal cord ischemia by clinical manifestations and histological changes. Selective intravascular occlusion determines minimal invasiveness and adequacy of the proposed model to in vivo pathological processes. This model of spinal cord ischemia can be used in experimental pharmacology for evaluation of neuroprotective activity of various drugs and bioactive substances.

[Protective effect of cyclopentyladenosine in a minimally invasive model of acute cerebral focal ischemia in rats]. / Zashchitnoe deistvie tsiklopentiladenozina na maloinvazivnoi modeli ostroi fokal'noi ishemii golovnogo mozga u krys.

The neuroprotector properties of cyclopentyladenosine (CPA), an adenosine receptor agonist, were studied on a model of focal brain ischemia in rats (reproducing a clinical pathological process in humans). The model of the focal brain ischemia in rats was induced by intravasal occlusion of left carotid artery, middle cerebral artery, and by bilateral occlusion of both carotid arteries. CPA was introduced by intracerebroventricular injections in a dose of 25 micrograms/kg, 60 min before ischemia induction. The protective effect was judged by comparing the neurological and histopathological disturbances in the control (untreated ischemia) and on the CPA background. CPA injections produced a pronounced neuroprotector effect on the minimum-invasive focal brain ischemia model in rats.

[Protective effect of adenosine receptor agonists in a model of spinal cord injury in rats]. / Zashchitnoe deistvie agonistov adenozinovykh retseptorov na modeli travmaticheskogo povrezhdeniia spinnogo mozga u krys.

Possibilities of the neuroprotector therapy using adenosine and cyclopentyladenosine (CPA), an adenosine receptor agonist, were studied on a model of spinal cord injury by compression in rats (most closely reproducing the analogous clinical pathological process in humans). The model was induced by slow, graded compression of the spinal cord at the thoracic level. Adenosine and CPA were introduced 60 min before injury by subcutaneous injections in a dose of 300 and 2.5 micrograms/kg, respectively. The protective effect was judged by comparing the neurological, electromyographic, and histopathological changes in animals with the model injury and in the control group (adenosine and CPA background). The A1-agonist CPA injections produced a pronounced, statistically significant neuroprotector effect on the given spinal cord injury model in rats. The neuroprotective effect of adenosine was significant but not as strong. It is concluded that it is expedient to use A-agonists in clinics.

[Minimum-invasive model of the rat brain focal ischemia]. / Maloinvazivnaia model' fokal'noi ishemii golovnogo mozga u krys.

The problem of brain ischemia damage treatment stimulates the search for new effective methods, which are studied on various experimental models. Most of such models possess significant disadvantages, producing hypoxia in the whole organism, being poorly controlled, involving serious traumas, and still being far from true pathological mechanisms accompanying the ischemia development. A model of focal brain ischemia in rats, induced by middle cerebral artery intravasal occlusion, is free of these disadvantages.

[The biological range and characteristics of the importance of adenosine receptors for the resistance of the brain to total ischemia]. / Biologicheskaia shirota i osobennosti znacheniia adenozinovykh retseptorov dlia ustoichivosti golovnogo mozga k polnoi ishemii.

In the total brain ischemia the cerebroprotective effect (CPE) of adenosine was pronounced in the following order: mouse > rat approximately guinea pig (males > females). The sensitizing effect (SE) of theophylline is the same in different species but is more pronounced in females compared to males. Newborn rats are much more tolerant to the total brain ischemia. The adenosine CPE increases and the theophylline SE decreases with age. The adenosine receptor component, evidently, contributes greatly to the natural tolerance of newborn animals to the total brain ischemia.

[The effect of adenosine receptor agonists on the normal cerebral blood flow and in subsequent ischemia]. / Vliianie agonistov adenozinovykh retseptorov na mozgovoi krovotok v norme i pri posleduiushchei ishemii.

Nonconformity of arterial pressure (AP) and cerebral blood flow (CBF) to the normal distribution necessitates the use of nonparametric criteria. Cerebroprotective doses of adenosine and cyclohexyladenosine significantly decrease AP and reduce (or virtually do not change) CBF. In conditions of following occlusion of carotid arteries AP is lower and CBF is somewhat better or the same as in the control (ischemia). Changes in CBF can be only an additional contribution to the high cerebroprotective effect of the A-receptor agonists.

[The comparative characteristics and receptor mechanism of the effect of adenosine-receptor agonists in total cerebral ischemia]. / Sravnitel'naia kharakteristika i retseptornyi mekhanizm éffekta agonistov adenozinovykh retseptorov pri polnoi ishemii golovnogo mozga.

The duration of gasping has no normal distribution, so nonparametric statistic criteria should be used. Three adenosine receptor agonists have a highly cerebro-protective effect which decreases in the order: N-ethylcarboxamide adenosine > > cyclohexyl adenosine > adenosine. Theophylline completely blocks these effects. Thus, they act through adenosine receptors. Adenosine receptor agonist are likely to protect themselves neurons.

[Protective effect of adenosine in total brain ischemia]. / Zashchitnyi éffekt adenozina pri polnoi ishemii golovnogo mozga.

Adenosine has prominent cerebro-protective effect at total brain ischemia. Other nucleotides and nucleosides are less active or have no effect at all. It suggests participation of A-receptors. Adenosine is more effective than 8 other drugs that have protective effect in different models of brain ischemia (nimodipine, gamma-hydroxybutyrate etc).