Klára Csete

Measurements of regional cerebral blood flow and blood flow velocity in experimental intracranial hypertension: infusion via the cisterna magna in rabbits.

Cerebral blood flow velocity, as measured in the intracranial segment of the internal carotid artery by transcranial Doppler sonography via the transorbital route, and regional cerebral blood flow and volume in corresponding cortical areas, as measured by the hydrogen clearance technique, were recorded for eight New Zealand White rabbits subjected to infusion via the cisterna magna to elevate intracranial pressure. In the lower range of autoregulation, that is, at perfusion pressures between 80 and 40 mm Hg and even lower, the changes in cerebral blood flow velocity and cerebral blood flow showed a strong correlation (0.86) under conditions of standard pCO2 (PaCO2 = 35 +/- 2 mm Hg). Autoregulation was exhausted at 40 mm Hg, and the cerebrovascular resistance was minimal. Below this perfusion pressure, the cerebral blood flow and volume dropped sharply, whereas the cerebrovascular resistance gradually increased, indicating that, despite the maximally dilated resistance vessels, intracranial hypertension causes vascular resistance to increase, possibly via blocking of the venous outflow. Our results confirmed that noninvasive and easily (even at bedside) applicable measurements of changes in cerebral blood flow velocity could be a substitute for the cumbersome and expensive isotope measurements of cerebral blood flow in patients with intracranial hypertension.

Effect of systemic administration of L-kynurenine on corticocerebral blood flow under normal and ischemic conditions of the brain in conscious rabbits.

&NA; Kynurenic acid, the only known endogenous antagonist of the excitatory amino acid receptors, exerts neuroprotective effect in focal cerebral ischemia. Kynurenic acid poorly while its bioprecursor, l‐kynurenine (L‐KYN) completely crosses the blood‐brain barrier. The aim of our study was to investigate the effect of intravenous l‐KYN (0.3, 1, and 3 mg/kg) on the normal and the unilateral carotid artery occlusion induced ischemic corticocerebral blood flow (cCBF) measured by hydrogen polarography in conscious rabbits. Administration of l‐KYN produced a significant increase in the normal cCBF; the peak values were recorded at the dose of 1 mg/kg (187% at 120 and 150 mins. respectively). The cCBF‐improving effect of l‐KYN was immediate and highly pronounced also in rabbits with carotid occlusion (peak value was 192% at 120 mins. at the dose of 1 mg/kg). Pretreatment with either atropine or N&ohgr;‐nitro‐L‐arginine‐methyl‐ester (L‐NAME) prevented the l‐KYN induced enhancement of the normal and the ischemic cCBF alike. It is suggested that the cCBF‐increasing effect of l‐KYN might be mediated by activation of cholinergic and nitric oxide pathways.

Effects of moxonidine on corticocerebral blood flow under normal and ischemic conditions in conscious rabbits

Hypertension associated with excessive liberation of circulating and tissue catecholamines is an independent risk factor for further cardiovascular complications and an important predictor of stroke. Moxonidine is a centrally acting anti-hypertensive drug with potent action on I1-imidazoline receptors. It inhibits catecholamine release and is therefore expected to exert an antiadrenergic effect at various levels in the regulation of the cardiovascular system. The aim of this study was to investigate the effect of moxonidine (0.025-0.1 mg/kg, i.v.) on the normal and unilateral carotid occlusion-induced impaired corticocerebral blood flow (cCBF) determined by hydrogen polarography, on mean arterial blood pressure (MABP) and heart rate (HR) in conscious rabbits. Moxonidine produced a reduction of MABP and HR. On the other hand, after administration of the drug, a significant increase in the normal and impaired cCBF was observed. Because the improvement in cCBF was conspicuous in both normal and ischemic conditions, moxonidine might be beneficial not only in the treatment of hypertension but also in the management of cerebral ischemia.

Influence of nitrovasodilators and cyclooxygenase inhibitors on cerebral vasoreactivity in conscious rabbits

Since the nitric oxide (NO) and cyclooxygenase pathways have been suggested to have important roles in most vasodilations, our aim was to study the influence of cyclooxygenase inhibitors and nitrovasodilators on cerebrovascular reserve capacity. Corticocerebral blood flow was measured by hydrogen polarography during hypercapnia and acetazolamide stimuli in conscious rabbits. The measurements were repeated in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin as nitric oxide synthase (NOS) and cyclooxygenase inhibitors. The effects of nitroglycerin and isosorbide-5-nitrate were also tested. L-NAME completely, while indomethacin markedly inhibited the hypercapnic corticocerebral blood flow response. Nitroglycerin and isosorbide-5-nitrate significantly attenuated hypercapnia elicited corticocerebral blood flow increase. The different treatments reduced only moderately the acetazolamide-induced corticocerebral blood flow response. These results lend support to the hypothesis that antithrombotic and antiinflammatory medication (cyclooxygenase inhibitors) and nitrovasodilator treatments could interfere with the measurement of cerebrovascular reactivity resulting in underestimation of the cerebrovascular reserve capacity in patients taking these drugs.

Disturbance of motoric function as behavioral measure of impaired cerebral circulation in mice

Aim of the present experiments was to elaborate an experimental model exhibiting the functional consequences of a moderate impairment of cerebral circulation sensitive enough for testing the long-term cerebroprotective effect of different drugs. In preliminary experiments mice survived unilateral occlusion of the carotid artery. This intervention, however, severely impaired the motor skill of the animals as measured by their activity on the rotating treadmill. Motimeter activity was also diminished following unilateral carotid occlusion. Somewhat unexpectedly, a more complex pattern of learned behavior in a one-trial learning passive avoidance paradigm was only modestly affected by unilateral carotid occlusion. Papaverine (2.0 mg/kg) normalized the motor incoordination measured on the rotating treadmill. The data suggest that impaired motoric function, as a result of unilateral carotid occlusion, might be a useful experimental tool to analyse functional consequences of impaired cerebral circulation and a sensitive test for screening of drugs with presumed cerebroprotective action.

Short tandem repeat data analysis in a Mongolian population

Fifteen somatic (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818, FGA) and five Y-chromosome (DYS19, DYS390, DYS391, DYS392, DYS393) short tandem repeat (STR) system analyses were carried out in a Mongolian population in order to define the possible relationship between Mongolians and old Hungarian population. For STR data analysis the Microsoft Excel-PowerStats program was used. Inter-population data analysis was performed with Arlequin Software ver. 2.000. The somatic markers showed meaningful difference between Mongolians and old Hungarians but the distribution of the Y-chromosome STR systems refers to a closer relationship between the old Hungarian and oriental populations.