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N Zarchin

Publications and source records attributed to N Zarchin.

30 records · Page 2Linked to original sources

Continuous multiparametric monitoring of brain activities following fluid-percussion injury in rats: preliminary results.

Severe head injury can result in a high mortality rate or irreversible brain damage. One technique used to induce traumatic brain injury (TBI) is exposure of the brain to fluid percussion pressure while monitoring the increase in intracranial pressure (ICP). Since brain injury is a multifactorial, pathological, time-dependent state, the multiparametric monitoring approach was adopted for studying fluid percussion effects on the rat brain. A multiprobe assembly (MPA) connected to the brain in vivo (right hemisphere) enabled the simultaneous monitoring of CBF, NADH redox state, extracellular K+, Ca2+, H+ levels as well as DC potential, ECoG and ICP. The animal was connected to the monitoring system and exposed to TBI after a recuperation period of at least 3 hours after the end of the operation. Two typical responses to TBI were recorded in our preliminary experiments. When severe injury was induced, ischemic depolarization (ID) developed, whereas mild or moderate injury led to repetitive spreading depression (SD) cycles. The relationship between the ID and SD observed under TBI is important to the understanding of the mechanism of brain injury. ICP before injury was between 2-6 mm Hg and increased to 20-22 mm Hg 2-3 minutes after the ID. After severe head injury, ICP remained high and in some cases increased to critical values causing death of these animals. Some animals developed seizures at various stages after the TBI. Hyperbaric oxygenation was used as a therapeutic tool to treat severely injured animals. These preliminary results suggest that it is feasible and practical to use the MPA approach for monitoring the brain after TBI.

Brain Injuries↗

Multiparametric monitoring of the awake brain exposed to carbon monoxide.

We have applied in vivo real-time techniques to monitor the physiological changes associated with exposure to a pattern of carbon monoxide (CO) known to cause brain oxidative stress. Using a multiparametric monitoring device connected to the brain, we exposed unanesthetized rats to two levels of CO, 0.1 and 0.3% in air. Energy metabolism was evaluated by the optical monitoring of relative cerebral blood flow (CBF) and intramitochondrial redox state. Ionic homeostasis was assessed by measurements of K+,Ca2+, and H+ or Na+ levels in the extracellular space. The electrical parameters monitored were the electrocorticogram and direct current steady potential. Under 1,000 ppm of CO, the CBF was increased significantly without any measurable change in the NADH redox state, suggesting that the cause for the increased CBF was not hypoxia. Exposing the awake rat to 1,000 ppm of CO (40 min) followed by 3,000 ppm of CO (20 min) led to an increase in CBF followed by episodes of spontaneous brain depolarizations characterized by changes in ionic homeostasis and blood flow. These changes were similar to those recorded under cortical spreading depression. In most animals exposed to 3,000 ppm of CO, spontaneous oscillations in CBF and NADH redox state that were negatively correlated were recorded. The results indicate that an inspired CO level of 0.1% had effects largely restricted to blood flow, whereas at a higher CO level an additional impairment in energy supply resulted in a complex pattern of effects similar to that caused by brain ischemia.

Animals↗

Brain mitochondrial redox state, tissue haemodynamic and extracellular ion responses to four-vessel occlusion and spreading depression in the rat.

Fibre-optic surface fluorometer reflectrometry was used to monitor the NADH (nicotine adenine dinucleotide) redox state from rat brain during three- or four-vessel occlusion. To compare the completeness of the electrocauterization of the vertebral arteries and the effectiveness of the anterior cerebral arteries, two light guides were implanted above the cerebral hemispheres. The NADH level was measured and correlated with the changes in the intensity of the reflected light at the excitation wavelength (366 nm) and to the ECoG (electrocorticogram). In the present study, we used ten rats in which unilateral and bilateral carotid occlusion were performed. In a second group of rats we tested the effects of four-vessel occlusion on the metabolic and extracellular K+ and Ca2+ activities as compared with those recorded under spreading depression conditions. These experiments were done by using the multiprobe assembly (MPA) approach. The results could be summarized as follows: (1) in the four-vessel occlusion model, the level of cerebral ischaemia could be estimated quantitatively, in real-time, by monitoring the NADH redox state; (2) unilateral carotid occlusion (after vertebral coagulation) led to a variable level of ipsilateral ischaemia, depending upon the blood flow compensation between the two hemispheres; (3) fibre-optic fluorometry enabled the correlation of NADH redox state with other physiological parameters as well as during after-brain ischaemia; (4) using the MPA in rats exposed to four-vessel occlusion as well as spreading depression, we identified the differences between the two pathological states, although there were some similarities in the ion homeostasis responses.

Animals↗

Brain metabolic responses to ischemia in the mongolian gerbil: in vivo and freeze trapped redox scanning.

The interrelation between the metabolic responses to ischemia and seizure propensity was studied in two groups of seizure prone (SP) and non-seizure prone (NSP) gerbils. The metabolic state was evaluated in vivo using the light guide surface fluorometry as well as in the frozen brain scanned at liquid N2 temperature for Fp/PN ratio after monitoring the brain in vivo. The results could be summarized as follows. (1) Unilateral carotid artery occlusion led to partial ischemia in the ipsilateral hemisphere while the contralateral hemisphere remained normoxic. (2) Animal variability in the degree of the ischemia insult due to unilateral occlusion was not side dependent or in correlation with seizure propensity. (3) Significant correlation was found between the NADH increase during ischemia and the redox state measurements done in the same brain after funnel freezing with liquid nitrogen. (4) In a large number of the gerbils (not depending on the origin or strain) a peculiar inter-hemispheric blood supply connection was found. A narrow band (1 mm in width) of tissue near the midline obtained its blood via the same vessels supplying the contralateral hemisphere. (5) We did not find any correlation between blood vessel anatomy to the brain and seizure propensity.

Animals↗

Factors affecting the oxygen balance in the awake cerebral cortex exposed to spreading depression.

Oxygen balance was evaluated in the cerebral cortex, using the surface fluorometry technique of the intramitochondrial NADH redox state, exposed to various physiological and pathological situations. Using flexible fiber optic light guide, connected to the brain surface via a cemented holder, the measurements were done continuously from the awake rat and gerbil. In few experiments the NADH redox state was correlated with the electrical and ionic activity (measured by surface K+ and DC electrodes). Three different animal models were used in the study: the adult rat, the very young rat (20 g) and the adult gerbil. Those 3 models were used in studying the effect of hypoxia, partial ischemia, and anesthesia on the metabolic and ionic activities measured from the awake brain. Spreading cortical depression (elicited by topical KCl solution) was used as a standard stimulation of the ionic and metabolic activities of the cerebral cortex. Two typical metabolic responses to spreading depression (SD) were recorded, namely 'oxidation cycle' and 'reduction cycle' depending upon the ability of the tissue to compensate for the extra amount of oxygen needed for the higher mitochondrial activity. It was found that the adult rat brain showed oxidation cycles in most conditions (besides partial ischemia), while the young rat and the gerbil brains were much more sensitive to the various perturbations of the brain and exhibited reduction cycle ( as a response to SD) under all pathological situations tested. We conclude from our detailed studies that the type of response to SD, as measured by NADH surface fluorometry, represents the oxygen balance which exists in the tissue under various conditions.

Animals↗

The effects of unilateral carotid occlusion on the responses to decapitation in the gerbil brain.

The effects of partial ischemia (unilateral carotid artery occlusion) on the metabolic and electrical responses to decapitation were studied in the awake and anesthetized gerbils' brains. The gerbil was connected to the 2 channel fluorometer/reflectometer by flexible light guides implanted above the two hemispheres of the brain. The results show that: (1) the metabolic rate as measured by this present technique is lower in the gerbil than in the rat; (2) the metabolic rate of the ischemic hemisphere is lower as compared to that of the normoxic contralateral hemisphere.

Animals↗

The effects of age on the metabolic and electrical responses to decapitation in the awake and the anesthetized rat brain.

The effects of age on the responses of the brain to decapitation (complete ischemia) were tested in the awake and anesthetized rat. The metabolic and reflected light activities were evaluated by the use of a DC fluorometer/reflectometer (one or two hemispheres) and the electrical activity was measured by electrocorticogram. In all 81 animals used in these experiments the above-mentioned parameters were measured, to enable comparison between the age groups. The rats were divided into six age groups ranging from 2 to 120 weeks and each age group was subdivided into awake and anesthetized animals. The results can be summarized as follows. (1) The rate of energy consumption was lower in the young (2 weeks) and the old rats (120 weeks) compared to the adult rats. (2) The effect of anesthetic was more pronounced in the young and the old rats than in the adult rats. (3) The electrical activity was in good correlation with the energy availability in all animals of various ages as well as in the awake and anesthetized rats.

Aging↗

Effects of age on the metabolic, ionic and electrical responses to anoxia in the newborn dog brain in vivo.

The interrelation between brain energy metabolism, electrical activity and ion homeostasis developing under experimental anoxia in animals of different ages is of significant value in the understanding of brain damage occurring under similar conditions of clinical neuropathology. The purpose of the present study was to compare brain energy states and extracellular ion homeostasis during anoxia in newborn puppies of various ages. We have developed and used a multiparametric monitoring device by which various functions of the brain can be recorded in a real-time mode from a 5 mm diameter area on the surface of the cortex. Intracellular oxygen balance was evaluated in newborn puppies of various ages by monitoring the intramitochondrial NADH redox state using a fluorescence technique. The electrical activity was measured by recording the spontaneous ECoG (electrocorticogram) and DC (direct current) steady potential. Ion homeostasis was evaluated using surface potassium and calcium mini-electrodes. Newborn puppies were anesthetized, the dura mater was removed and the multiprobe assembly was placed on the brain and cemented to the skull. Five groups of puppies (0-1, 2-7, 8-14, 15-21 days and 3-24 weeks) were exposed to 5 minutes of complete O2 deprivation (100% nitrogen exposure) and were monitored during the recovery period until all parameters returned to baseline values. The results may be summarized as follows: 1. Resting baseline levels of extracellular K+ were in the same range as described for other young and adult mammals (2.9 +/- 0.05 mM). 2. Extracellular Ca2+ levels were higher than those published for other mammals (1.6 +/- 0.07 mM). 3. During 5 minutes of anoxia, a significant increase in K+ levels was recorded. This increase was not accompanied by measurable changes in extracellular Ca2+. 4. The effect of age on the length of time to the elevation of the extracellular K+ concentration and on the rate of K+ accumulation from the onset of the anoxic condition was significant, i.e., the younger the animal the longer the time and the lower the rate. 5. The rate of energy depletion was age dependent as indicated by the rate of NADH accumulation during anoxia. However, no significant effect of age on the basal aerobic metabolism was found as measured by the maximum percent increase of NADH during anoxia.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗