Changes of circulatory-metabolic indices and skull biomechanics with brain activity during aging.

The cerebral blood flow values used in experimental and clinical investigations as the informative criteria for brain blood supply are often misleading. The correlation between the cerebral blood supply and brain function is not proven in all cases. An increase of brain activity is known to be accompanied by a rise of blood flow in activated regions, while a decreased activity results in a decreased blood flow. This demonstrates the close correlation between the brain blood supply and its activity. Such a correlation had not been noted in the age-dependent decrease of cerebral blood flow, suggesting the existence of special age-related mechanisms that develop with age to maintain brain metabolism. The biomechanical properties are of special significance as predicted in the early 20th century. Only recently were they validated by the simultaneous recording of Transcranial Dopplerogram and Rheoencephalogram with in-depth analysis focused on single cardiac cycles. Functioning of the intracranial blood and cerebrospinal fluid dynamics was integrated with a special physiological test "Prognosis-2" to measure brain cognitive function. Correlation was demonstrated with the circulatory-metabolic state of brain activity, especially in people with changing cognitive function. The data supports a conceptual model of adequate circulatory-metabolic supply of brain activity, showing the functional unity, which follows from integration of the mentioned systems.

Blood flow dynamics in different layers of the somatosensory region of the cerebral cortex on the rat during mechanical stimulation of the vibrissae.

The present work reports studies of the quantitative spatial and temporal characteristics of changes in local blood flow in different layers of the somatosensory cortex of rats during adequate mechanical stimulation of the vibrissae. Studies were performed using 34 Wistar rats. Skull trepanning was performed under urethane (1 g/kg) anesthesia. Television-guided microscopy was used to introduce a set of three platinum electrodes (100 microns in diameter, with tip diameters of 30-40 microns) into the somatosensory cortex projection zone of the vibrissae. The first and third electrodes were positioned in cortical layers I-III and IV-VI and the central electrode was used to generate hydrogen within the tissue. Electrode positions were confirmed histologically after experiments. Animals were placed on artificial ventilation and one or all vibrissae were stimulated at a frequency of 3 Hz for 60 sec, with interstimulus intervals of 3 min. Changes in the local blood flow were measured during stimulation and for 1 min afterwards, using the hydrogen clearance method, and brain tissue impedance was also measured. There was a small (up to 5-7%) reduction in blood flow in the first seconds of stimulation, which was followed 15-25 sec later by an increase and subsequent return to initial when stimulation stopped. The increases in blood flow during stimulation of all vibrissae were by 24.2 +/- 6.7% (n = 36) in layers IV-VI and 24.5 +/- 5.6% (n = 34) in layers I-III; increases in response to stimulation of single vibrissae were by 19.4 +/- 7.4% (n = 28) and 17.8 +/- 6.4% (n = 28) respectively. The dynamics of impedance changes corresponded to those of blood flow changes. Thus, heterogeneity was found in changes of local brain blood flow in different layers of the somatosensory cortex during increases in cortical functional activity.

Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain.

How neuronal activity changes cerebral blood flow is of biological and practical importance. The rodent whisker-barrel system has special merits as a model for studies of changes in local cerebral blood flow (LCBF). Stimulus-evoked changes in neural firing and 'intrinsic signals' recorded through a cranial window were used to define regions of interest for repeated flow measurements. Whisker-activated changes in flow were measured with intravascular markers at the pia. LCBF changes were always prompt and localized over the appropriate barrel. Stimulus-related changes in parenchymal flow monitored continuously with H2 electrodes recorded short latency flow changes initiated in middle cortical layers. Activation that increased flow to particular barrels often led to reduced flow to adjacent cortex. Dye was injected into single penetrating arterioles from the pia of the fixed brain and injected into arterioles in slices of cortex where barrels were evident without stains. Arteriolar and venular domains at the surface were not directly related to underlying barrels. Capillary tufts in layer IV were mainly coincident with barrels. The matching between a capillary plexus (a vascular module) and a barrel (a functional neuronal unit) is a spatial organization of neurons and blood vessels that optimizes local interactions between the two. The paths of communication probably include: neurons to neurons, neurons to glia, neurons to vessels, glia to vessels, vessels to vessels and vessels to brain. Matching a functional grouping of neurons with a vascular module is an elegant means of reducing the risk of embarrassment for energy-expensive neuronal activity (ion pumping) while minimizing energy spent for delivery of the energy (cardiac output). For imaging studies this organization sets biological limits to spatial, temporal and magnitude resolution. Reduced flow to nearby inactive cortex enhances local differences.

LCBF changes in rat somatosensory cortex during whisker stimulation monitored by dynamic H2 clearance.

We evaluated increases in local cerebral blood flow (LCBF) localized to single activated cortical columns by H2 clearance methods. The rat whisker-barrel cortex is a model for cortical function and neural processing in active explorative behaviors. Up to four 30-40 microns Pt wire electrodes were inserted in or near the rat whisker-barrel cortex. Electrode positions were mapped by postmortem histology. H2 was generated electrochemically by constant current from one electrode and detected by one or more other electrodes 300-500 microns away. Changes in LCBF produced inverse changes in PH2. Shifts during steady H2 generation were calibrated against standard H2 inhalation clearance curves at rest and during inhalation of 7.5% CO2 for 1 min for quantitative estimates of LCBF. Contralateral whisker stimulation at 3 Hz, 1 min duration and delivered every 2 min produced the largest increases in LCBF. LCBF responses were detected in approximately 1 s. Stimulation of single whiskers produced the largest responses when an electrode was in the corresponding barrel. These results indicate that increased neural activity in a single cortical column produces blood flow responses primarily in that column.

Cerebral blood flow and tissue pO2 changes following local met-enkephalin administration in awake, freely moving cats.

The effect of locally administered methionine-enkephalin on cerebrocortical blood flow and tissue pO2 was tested in chronic, awake, freely moving cats. Local cortical blood flow was measured with the H2-gas clearance method, and cortical pO2 in the same area was monitored with a polarographic technique using double Pt electrodes. Met-enkephalin was administered with a micropipette technique in 0.1, 0.5, 1.0 and 5.0 mumol/l concentrations in 20 microliters volume. Met-enkephalin caused a marked, dose dependent decrease of the cortical flow as well as of the cortical pO2. Following 5.0 mumol/l met-enkephalin the flow decreased more (x = 30.6%) than did the pO2 (x = 18%). The maximum effect could be observed 2-7 min following administration of the peptide, the duration of the effect was about 20 min. The threshold dose was found around 5-7 X 10(-8) M/l. Met-enkephalin in the above mentioned doses caused no vegetative, motor or behavioural changes in these experiments.

Functional steadiness of the cerebral circulatory system under altered gravitational conditions.

The maintenance of hemodynamic stability is a functional characteristic of the cerebral circulatory system. This characteristic developed during the evolutionary process. It can be of use as an indicator of the activity of the central processes regulating cerebral blood flow under different stress conditions, particularly, during a long space mission. Rheoencephalographic methods are qualitative and yield information that permits assessment of the changes in the functional status of the cerebral circulatory system. This was confirmed by results obtained during the Salut-4 space mission. The observations permitted us to assess indirectly the status of the cosmonauts.

Hypothalamic and thalamic blood flow during somatic afferent stimulation in dogs.

The effect of somatic afferent C fiber stimulation on regional cerebral blood flow (rCBF) and cerebral tissue available oxygen (aO2) was studied in 20 dogs under chloralose anesthesia. Mean arterial blood pressure, arterial Pco2, and pH were stabilized before and during the 3-min stimulation of the sciatic nerves (20 V, 300 ms, 15 Hz). Combined gold+platinum electrodes were chronically implanted into the ventral posterolateral nucleus of the thalamus, ventromedial nucleus of the hypothalamus, and into the white matter. Tissue aO2 and rCBF of these regions were measured polarographically, the latter by the H2-gas clearance technique. Blood flow changed from 42 +/- 2.1 to 28 +/- 1.7 ml/100 g per min (cerebrovascular resistance (CVR), from 2.91 +/- 0.29 to 4.31 +/- 0.52 resistance units (RU) in the thalamus, from 59 +/- 5.0 to 47 +/- 5.0 ml/100 g per min (CVR: from 2.46 +/- 0.28 to 2.92 +/- 0.35 RU) in the hypothalamus, and from 21 +/- 1.0 to 17 +/- 0.8 ml/100 g per min (CVR: from 6.367 +/- 0.35 to 7.672 +/- 0.40 RU) in the white matter during ipsilateral stimulation. Contralateral stimulation of the sciatic nerves caused a more moderate but likewise significant drop in rCBF and an increase in CVR except in the white matter. Parallel to these changes, tissue aO2 decreased by 25 +/- 2% in the thalamic and by 19 +/- 2% in the hypothalamic area, relative to the prestimulation level.

Investigation of human cerebral circulation in spaceflight conditions.

The effective control of the main physiological systems during spaceflight and investigation of the mechanisms involved is a difficult problem, but the success of manned space missions greatly depends on the solution of these problems. In this respect, the cerebral circulation system is of particular importance for control and research. The large amount of experimental evidence concerning the functional peculiarities of the cerebral circulation system gives us every reason to suggest that this part of the circulatory system could be readily affected by spaceflight dynamic factor-accelerations and weightlessness.