Masahiro Kobari

Familial idiopathic brain calcification with autosomal dominant inheritance

Article abstract-We report a family with brain calcification, predominantly in the basal ganglia, and no evident cause such as abnormal calcium or phosphorus metabolism. The proband, a 48-year-old man, had intellectual decline, parkinsonism, and mild cerebellar ataxia. He had bilateral and symmetric calcification of the basal ganglia, thalamus, dentate nucleus, cerebral cortex, subcortical white matter, and hippocampus on CT. Calcified areas showed low- or high-intensity signals on MRI T sub 1-weighted images, and low-intensity signals on MRI T2-weighted images. Two sons and both parents, all asymptomatic, also showed calcification of the basal ganglia, suggesting an autosomal dominant inheritance. Familial idiopathic brain calcification is a rare disorder with less than 20 previously reported families. Twelve families with autosomal dominant inheritance showed a relatively homogeneous clinical picture, which may represent a distinct clinical entity. Mental deterioration, parkinsonism, and cerebellar ataxia appear in adult life and progress gradually. CT imaging, rather than MRI, is a simple and useful means to screen family members for this condition. NEUROLOGY 1997;48: 645-649

Role of nitric oxide in regulation of cerebral microvascular tone and autoregulation of cerebral blood flow in cats.

The role of nitric oxide in the regulation of cerebrocortical microvascular tone and autoregulation of cerebral blood flow (CBF) was examined in 24 anesthetized cats. The local cerebral blood volume (CBV), mean transit time of blood (MTT), and CBF in the cortex were measured by our photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels. Intravenous injection of 0.35-0.7 mg/kg/min NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, significantly increased mean arterial blood pressure (MABP; 8.4-14.1%, P < 0.01), decreased CBV (15.2-28.7%, P < 0.01), and decreased CBF (20.0-29.8%, P < 0.01) in a dose-related manner. The changes in MABP, CBV, and CBF elicited by L-NMMA were inhibited (P < 0.05) by simultaneous infusion of 35 mg/kg/min L-arginine. Autoregulation of CBF was examined during controlled hypotension of -30 to -40 mmHg (artificial bleeding) and recovery of blood pressure (reinfusion of blood). Although CBF remained constant with blood pressure changes in the control state (delta CBF/delta MABP of 0.037 +/- 0.155 with hypotension), CBF became dependent on blood pressure changes (delta CBF/delta MABP of 0.478 +/- 0.135, P < 0.05) during infusion of 0.35 mg/kg/min L-NMMA. It is concluded that nitric oxide participates in both the regulation of basal tone of cerebral microvessels and the autoregulation of CBF.

Transient cerebral vasodilatory effect of neuropeptide y mediated by nitric oxide

The effects of intracarotidly injected neuropeptide Y (NPY; 0.1 micrograms/kg) on the local cerebral blood volume (CBV) and blood flow (CBF) in the parieto-temporal cortex were examined by the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative crosssectional area of the cerebral microvascular beds. NPY immediately caused transient but significant increases in CBV and CBF, which lasted for less than 5 min. Thereafter, CBV returned to and remained at the control level, although CBF was decreased by 30-40% for 60 min during the monitoring period. The CBV increases after NPY were prevented by a 15-min preinjection of 0.35 mg/kg/min of NG-monomethyl-L-arginine (L-NMMA), which is a competitive blocker of nitric oxide synthesis. The CBV increases after NPY reappeared following a 15-min administration of 0.25 mg/kg/min of L-arginine, which is a precursor of nitric oxide. We conclude that NPY administered in vivo exerts a previously unreported effect of transient vasodilatation on the cerebral microvessels. This action appears to be mediated by nitric oxide, which is a major candidate as an endothelium-derived relaxing factor (EDRF).

Bilateral hemispheric reduction of cerebral blood volume and blood flow immediately after experimental cerebral hemorrhage in cats.

Acute cerebral circulatory changes following experimental cerebral hemorrhage were investigated in eight cats. The cerebral hemorrhage was produced in the right basal ganglia by introducing arterial blood via a thin catheter, using the systemic arterial blood pressure of the cat as a driving force. Local cerebral blood volume was measured continuously in the bilateral parietotemporal cortexes employing photoelectric apparatuses. Carbon black dilution curves were recorded from the regions, and the mean transit time of blood was calculated. Local cerebral blood flow was estimated from mean transit time and cerebral blood volume. Intracranial pressure was monitored continuously in the right parietal epidural space. Five minutes after cerebral hemorrhage, intracranial pressure increased by 24.0 +/- 6.1 mm Hg, while mean arterial blood pressure increased by only 2.9 +/- 2.0 mm Hg. Cerebral blood volume decreased by 1.60 +/- 0.24 vol% in the hemorrhagic and 1.14 +/- 0.30 vol% in the nonhemorrhagic hemisphere. Cerebral blood flow decreased by 30.0 +/- 4.5 ml/100 g brain/min in the hemorrhagic (initially 64.5 +/- 13.6) and by 30.3 +/- 7.5 ml/100 g brain/min in the nonhemorrhagic (initially 60.9 +/- 6.9) hemisphere. Increased intracranial pressure appeared to be the main cause of the observed cerebral blood volume/flow reduction shortly after experimental hemorrhage in the basal ganglia. Several other factors and mechanisms involved are discussed.

Repetitive concentric wave-ring spread of oligemia/hyperemia in the sensorimotor cortex accompanying K+-induced spreading depression in rats and cats

Vascular changes accompanying spreading depression (SD) remain controversial. We examined dynamic alterations of local cerebral blood volume (CBV) during SD by observing light transmission at an isosbestic point of hemoglobin (550 nm) in seven rats and five cats under alpha-chloralose/urethane anesthesia. The two species were used for comparison between the lissencephalic and gyrencephalic brains. We found that a concentrated K(+) solution microinjected into the sensorimotor cortex provoked CBV changes that appeared as a repetitive propagation of concentric wave-rings of ischemia followed by hyperemia expanding peripherally from the injection site at speeds of 1.9-3.2 mm/min. The dynamic CBV changes continued repeatedly every 1-5 min for more than 30 min in three rats, ceased within 30 min in three rats and remained at the site of K(+) injection in one rat. Similar repeated CBV changes occurred in two out of five cats.

Levodopa-induced local cerebral blood flow changes in Parkinson's disease and related disorders

Local cerebral blood flow (CBF) in the steady state and after intravenous administration of levodopa (1 mg/kg) was measured by xenon-enhanced computed tomography in patients with Parkinsons disease (PD, n = 16), progressive supranuclear palsy (PSP, n = 6), olivopontocerebellar atrophy (OPCA, n = 5), and arteriosclerotic parkinsonism (AP, n = 7). Three patterns of local CBF changes following levodopa were observed: (1) diffuse CBF increases, especially in striatum and thalamus, as found in patients with PD; (2) no significant changes in CBF, as in patients with OPCA and AP; and (3) CBF reductions in basal ganglia and thalamus, as seen in patients with PSP. The CBF increases after levodopa in PD may be secondary to metabolic activation of the nigrostriatal dopaminergic system. The poor CBF responses in patients with OPCA, AP, and PSP appeared to reflect degeneration of the dopaminergic neurons and dopamine receptors to various degrees. The CBF increases, especially in striatum and thalamus, tended to be greater (not significant) among responders to oral levodopa therapy. Levodopa-induced CBF measurements may be useful for the differential diagnosis of parkinsonian syndromes of various etiologies, but are not necessarily sufficient for predicting outcomes of long-term levodopa therapy.

Dilatation of cerebral microvessels mediated by endothelin ETB receptor and nitric oxide in cats

The functional role of the endothelin (ET)B receptor in the cerebral microvessels was examined in seven anesthetized cats. The effects of intracarotidly injected IRL1620, a selective ETB receptor agonist, on the cerebral blood volume (CBV) in the cortex were examined by a photoelectric method. CBV reflects the cumulative dimensions of the cerebral microvessels. High doses of IRL1620 (0.1-1 nmol/kg) elicited a transient fall in CBV, followed by a marked and dose-related increase of CBV (P < 0.01). The CBV increase was significantly inhibited (P < 0.01) by simultaneous administration of 0.35 mg/kg/min NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis. The marked, but transient, depressor effect of IRL1620 was also attenuated (P < 0.01) by L-NMMA. The ETB receptor subtype and production of nitric oxide, probably in the endothelium, mediate the vasodilatory action of ET in the cerebral microvessels.

Comparison between pial and intraparenchymal vascular responses to cervical sympathetic stimulation in cats. Part 1. Under normal resting conditions

To investigate the role of sympathetic regulation in both resistance and capacitance vessels in cerebral circulation, the responses of pial and intraparenchymal vessels to sympathetic nerve stimulation were simultaneously examined in 14 cats by means of a newly developed video camera photoelectric system. The system consisted of a video camera system for measurement of pial vascular diameters and a photoelectric apparatus for estimating regional cerebral blood volume in the intraparenchymal vessels. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min. Initially, both the pial and intraparenchymal vessels constricted. The large pial arteries (173 ± 25 μm, mean ± SEM) remained constricted throughout the stimulation, whereas the intraparenchymal vessels began to dilate after the initial constriction and exceeded the control level at 175 ± 25 s despite continued stimulation. In conclusion, such sympathetic nerve stimulation is considered to exert a constrictive effect on the intraparenchymal as well as the pial vessels at the early stage. The compensatory dilation of the intraparenchymal vessels was delayed 3 min after initiation of the stimulation.

Comparison between the Photoelectric Method and H2 Clearance Method for Measuring Cerebrocortical Blood Flow in Cats

The photoelectric method using carbon black as a nondiffusible tracer of blood was compared with the hydrogen clearance (H2) method in nine anesthetized cats. A photoelectric apparatus and H2 electrode were applied to a small region of the cerebral cortex (left ectosylvian gyrus) for simultaneous measurement of the regional CBF. The values of CBF(H2) and CBF(photoelectric) were 50.7 ± 19.2 and 52.1 ± 14.5 ml − 100 g−1 · min−1, respectively. CBF(H2) and CBF(photoelectric) were found to correlate well (r = 0.588, p < 0.01) when changes in CBF were induced by CO2 inhalation, exsanguination, hyperventilation, and occlusion of the middle cerebral artery. The correlation between CBF(H2) and CBF(photoelectric) was much better in the case of intraindividual comparisons (r = 0.957, p < 0.01). In addition to its merits in common with the H2 clearance method, such as handiness, low cost, and strict regionality, the photoelectric method displayed the following advantages: time-to-time measurements of CBF (<20 s), immediate display of the microcirculatory flow pattern, and simultaneous monitoring of cerebral blood volume. However, measurements from deep structures of the brain are better performed by the H2 method despite the disadvantage of the use of a potentially explosive gas.

Video Camera Method for Simultaneous Measurement of Blood Flow Velocity and Pial Vessel Diameter

A new method for the simultaneous measurement of blood flow velocity and pial vessel diameter is described. The system consists basically of a high-sensitivity vidicon camera, camera control, width analyzer, video densitometer, TV monitor, desktop computer, and multi-pen recorder. The pial vessels are visualized through a cranial window at 25–200x magnification on the TV monitor. The diameter of three target vessels can be recorded simultaneously on the recorder by adjustment of controllable video signal gates using the width analyzer. At the same time, the optical densities of two targets at points upstream and downstream of the pial vessel are measured continuously with video densitometers, and their outputs are recorded on the polygraph and analyzed by the computer. The time difference in the two peaks of time–con centration curves, produced every 2–3 s at the highest frequency by the injection of a small amount of saline through the lingual artery, is measured on-line using the computer. The flow velocity in the vessel is calculated from the time difference and the distance between the two targets. The system was shown to be stable, reliable, and rapid in response. This method may provide a useful tool for research in the field of blood circulation in the brain or any other organ.