Spread of fast thermowaves through the cerebral cortex produced by visual stimulation

Thermowaves spreading through the cerebral cortex were observed and investigated during acute experiments on white rats using a new technique — that of thermoencephaloscopy (TES) through the intact skull. These waves were induced by regular visual stimulation (at intervals of 1.5–3 min) or by initiating one of the flashes and spread through the cortex along trajectories of five basic types; amplitude of thermowaves: 0.005–0.1°C; length: 10–15 mm; duration 1.2–11.4 sec; velocity: 1–33 mm/sec; extent of pathway: 2–56 mm. They appeared with a high degree of probability (of 0.92) during the interval between 15 sec before and 26 sec after the flash. Numbers of moving waves declined by the point of stimulus application and rose by 7–8 sec after the flash. Waves arose in 50% of cases in the contralateral visual cortex (areas 17 and 18a), spreading to the midline and crossing to the ipsilateral hemisphere (areas 17, 18a, and 7). Local waves moving along a circular trajectory were also discovered in the contralateral visual cortex. Several types of wave, differing in trajectory, also arose in the ipsilateral visual cortex. Mechanisms and possible significance of this effect are examined.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 4, pp. 467–475, July–August, 1989.     

Sensory mapping of the rat cerebral cortex by thermographic methods

Using thermovision and digital image processing, the dynamics of thermomap in the brain cortex has been studied on albino rats through the opened skull before and during sensory stimulation. Photic, sonic and somatosensory stimuli lead to the onset of local heating foci in the corresponding cortical zones, as well as to local multiple thermoresponses in other areas. Some quantitative parameters of these effects are given and their possible mechanisms are discussed.     

Spatial characteristics and the dynamics of the activation foci in the cortex during the elaboration of a conditioned reflex (thermographic research)

In acute experiments on immobilized white rats, by thermovision methods and digital image processing, spatial distribution and dynamics of local heating and cooling of dorsal surface of the cerebral cortex was studied through intact skull during elaboration of a conditioned reflex. Distant and noninvasive thermovision methods allowed to reveal and quantitatively study local cortical thermal reactions in the somatosensory and motor cortex and in the cerebellum in the process of elaboration and testing of conditioned connection. Under discussion are mechanisms, properties and significance of these effects for investigation of learning.     

Movement of thermowaves over the cerebral cortex in the white rat

Thermal spatial distribution and temperature pattern were recorded using techniques of thermovision and digital image processing through the intact skull during acute experiments on white rats immobilized using myorelaxants or anesthetized with Nembutal. Under certain circumstances faint cortical thermowaves of 0.2-0.1°C were seen to arise and move 8–30 mm across the cortex for 2–9 sec at a speed of 2–10 mm per sec. One of the trajectories of movement detected was circular in shape; the thermowave would start off in one hemisphere, spread across it in either direction, and cross to the other hemisphere. It would then move through the second hemisphere to the opposite side and finally return to the original area. Movement of the waves also followed linear and arc-shaped trajectories, sometimes but not always crossing over to the opposite hemisphere. The mechanisms and implications of this phenomenon are discussed.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 340–346, May–June, 1986.     

TRAIL-Based High Throughput Screening Reveals a Link between TRAIL-Mediated Apoptosis and Glutathione Reductase,a Key Component of Oxidative Stress Response

A high throughput screen for compounds that induce TRAIL-mediated apoptosis identified ML100 as an active chemical probe, which potentiated TRAIL activity in prostate carcinoma PPC-1 and melanoma MDA-MB-435 cells. Follow-up in silico modeling and profiling in cell-based assays allowed us to identify NSC130362, pharmacophore analog of ML100 that induced 65-95% cytotoxicity in cancer cells and did not affect the viability of human primary hepatocytes. In agreement with the activation of the apoptotic pathway, both ML100 and NSC130362 synergistically with TRAIL induced caspase-3/7 activity in MDA-MB-435 cells. Subsequent affinity chromatography and inhibition studies convincingly demonstrated that glutathione reductase (GSR), a key component of the oxidative stress response, is a target of NSC130362. In accordance with the role of GSR in the TRAIL pathway, GSR gene silencing potentiated TRAIL activity in MDA-MB-435 cells but not in human hepatocytes. Inhibition of GSR activity resulted in the induction of oxidative stress, as was evidenced by an increase in intracellular reactive oxygen species (ROS) and peroxidation of mitochondrial membrane after NSC130362 treatment in MDA-MB-435 cells but not in human hepatocytes. The antioxidant reduced glutathione (GSH) fully protected MDA-MB-435 cells from cell lysis induced by NSC130362 and TRAIL, thereby further confirming the interplay between GSR and TRAIL. As a consequence of activation of oxidative stress, combined treatment of different oxidative stress inducers and NSC130362 promoted cell death in a variety of cancer cells but not in hepatocytes in cell-based assays and in in vivo, in a mouse tumor xenograft model.     

The cholinergic system of the forebrain modulates the activity of the GABA-ergic interneurons which realize presynaptic regulation in the neocortex of kittens

It has been found that at the end of the second week of postnatal life, stimulation of cholinergic ascending paths causes a selective inhibition of cortical neurones reaction to sensory stimulation, without influencing the background activity. The observed inhibition is blocked both by atropine and picrotoxin, but not by bicuculline. It is suggested that the observed phenomenon characterizes, presynaptic control of cortical neurones activity in the early ontogenesis. This inhibition is formed on the basis of cooperative choline- and GABA-ergic brain systems participation and is performed not through GABA-receptors.     

Dynamic thermal mapping of rat brain during sensory stimulation and spreading depression

Using both techniques of thermovision and statistical analysis of thermal imaging, dynamics of temperature distribution over the dorsal surface of the brain were investigated through the intact skull during acute experiments on white rats. Both diffuse and regionally specific cerebral thermal reactions were observed during visual, acoustic, and somatosensory stimulation, together with multiple local thermal response, often following a specific pattern. These outline thermal effects differing from the compartment of the brain to another in degree, stability, and point of onset. Temperature waves developed together with spreading depression, produced in the cortex by injecting KC1. Once investigations had been performed this response could be divided into diffuse and spatially ordered components. The possible mechanisms of this thermal imaging of brain processes are discussed, together with how they are linked with changes in cerebral blood flow and neuronal metabolic thermal production.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Institute of Radio Engineering and Electronics, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 18, No. 1, pp. 26–35, January–February, 1986.