Blood Flow In Ischemic Brain Research Articles

Изучение антиагрегационного и противоишемического действия мемантина и 5-гидроксиадамантан-2-она у пациентов с цереброваскулярной патологией и в эксперименте

Изучено действие 2 производных адамантана – мемантина и 5-гидроксиадамантан-2-она – на агрегацию тромбоцитов у пациентов с цереброваскулярной патологией. В исследованиях in vitro показано, что 5-гидроксиадамантан-2-он, в отличие от мемантина, в большинстве наблюдений обладает антиагрегационной активностью. В экспериментах установлено, что антагонист NMDA-рецепторов мемантин снижает мозговой кровоток в коре мозга крыс как интактных, так и в условиях глобальной преходящей ишемии, тогда как 5-гидроксиадамантан-2-он, обладающий ГАМК-ергическим механизмом действия, напротив, избирательно улучшает кровоснабжение ишемизированного мозга и при этом превосходит препарат сравнения нимодипин. Полученные данные указывают на ведущую роль ГАМК-ергических механизмов в реализации цереброваскулярной противоишемической активности препаратов.

Abstract 3576: Selective Inhibition Of Rho-kinase Type 2 In Ischemic Stroke

Background and aims: Rho/Rho-associated protein kinase (ROCK) pathway plays a pivotal role in the pathogenesis of vascular diseases including stroke. Indeed, ROCK inhibitors improve cerebral blood flow in ischemic brain, and are neuroprotective in a variety of experimental ischemia models. Evidence suggests that ROCK type 2 (ROCK2) is more relevant in acute stroke treatment. We tested the neuroprotective efficacy and safety of a novel selective small-molecule ROCK2 inhibitor, SLx-2119, in ischemic stroke, and characterized the dose-response and therapeutic window. Methods and results: All experiments were conducted by a blinded investigator. Mice were anesthetized with isoflurane (2.5% induction, 1.2% maintenance, in 70% N2O/30% O2), and subjected to 1h transient middle cerebral artery occlusion (MCAO) using an intraluminal filament inserted via the external carotid artery. Regional CBF was monitored using a laser Doppler probed placed over the core MCA territory. Neurological deficits were assessed before sacrifice at 48h, using five-point grading. Indirect infarct volumes were calculated using 1mm-thick TTC-stained coronal sections. SLx-2119 (50-300 mg/kg) or vehicle was administered via orogastric gavage (in 0.4% methylcellulose) every 12h until 48h after reperfusion. When started 24h before MCAO (pre-ischemic treatment), SLx-2119 produced a dose-dependent decrease in infarct volume (37% decrease at 200 mg/kg and 26% decrease at 100 mg/kg) compared to vehicle treated group. Post-ischemic treatment with SLx-2119 (200 mg/kg) remained efficacious when initiated 1h (34% decrease in infarct volume) or 3h (21% decrease in infarct volume), but not 6h after MCAO, suggesting a therapeutic window between 3-6h after stroke onset in mice. SLx-2119 also improved neurological deficits, but did not alter CBF reduction in the ischemic core, systemic arterial pressure, pH or blood gas values, or mortality. Conclusions: These data suggest that selective ROCK2 inhibition improves tissue and neurological outcome in acute stroke, with an efficacy comparable to that previously reported for non-selective ROCK inhibitors. Unlike non-selective ROCK inhibitors, ROCK2 inhibition does not precipitate hypotension, an important dose-limiting side effect in acute stroke.

Pulsatile versus Nonpulsatile Blood Flow in the Treatment of Acute Cerebral Ischemia

The effects of pulsatile and nonpulsatile perfusion on local cerebral blood flow (CBF) and on computerized mapping (CME) of electroencephalograms (EEG) in nonischemic and ischemic brain were studied using a canine stroke model. Nine anesthetized mongrel dogs were placed on normothermic right atrial-femoral artery cardiopulmonary bypass at a flow of 100 ml/kg/minute. Local CBF measurements and CME data were collected during nonpulsatile perfusion and maximal pulsatile perfusion. The stroke model was then produced, and local CBF measurements and CME data were again collected during nonpulsatile and pulsatile perfusion. In the nonischemic brain, local CBF increased 19%, from 32 +/- 10 to 38 +/- 11 ml/100 g/minute (P less than 0.01), when perfusion was changed from nonpulsatile flow (pulse pressure less than 4mm Hg) to pulsatile flow (pulse pressure 39 +/- 11 mm Hg). In the ischemic brain, local CBF increased 55%, from 11 +/- 5 to 17 +/- 7 ml/100 g/minute (P less than 0.01), when perfusion was changed from nonpulsatile (pulse pressure less than 3 mm Hg) to pulsatile (pulse pressure 36 +/- 7) flow. EEG power data, expressed as a power ratio index (PRI = low frequency power/high frequency power), improved significantly, from 110 +/- 33 to 101 +/- 41 (P less than 0.01) with pulsatile perfusion. These data demonstrate the importance of pulsatile blood flow in ischemic brain.

Pulsatile versus nonpulsatile blood flow in the treatment of acute cerebral ischemia

The effects of pulsatile and nonpulsatile perfusion on local cerebral blood flow (CBF) and on computerized mapping (CME) of electroencephalograms (EEG) in nonischemic and ischemic brain were studied using a canine stroke model. Nine anesthetized mongrel dogs were placed on normothermic right atrial-femoral artery cardiopulmonary bypass at a flow of 100 ml/kg/minute. Local CBF measurements and CME data were collected during nonpulsatile perfusion and maximal pulsatile perfusion. The stroke model was then produced, and local CBF measurements and CME data were again collected during nonpulsatile and pulsatile perfusion. In the nonischemic brain, local CBF increased 19%, from 32 +/- 10 to 38 +/- 11 ml/100 g/minute (P less than 0.01), when perfusion was changed from nonpulsatile flow (pulse pressure less than 4mm Hg) to pulsatile flow (pulse pressure 39 +/- 11 mm Hg). In the ischemic brain, local CBF increased 55%, from 11 +/- 5 to 17 +/- 7 ml/100 g/minute (P less than 0.01), when perfusion was changed from nonpulsatile (pulse pressure less than 3 mm Hg) to pulsatile (pulse pressure 36 +/- 7) flow. EEG power data, expressed as a power ratio index (PRI = low frequency power/high frequency power), improved significantly, from 110 +/- 33 to 101 +/- 41 (P less than 0.01) with pulsatile perfusion. These data demonstrate the importance of pulsatile blood flow in ischemic brain.