Effects of fluid percussion injury on rat brain hemodynamics, ionic, electrical activity, and energy metabolism in vivo.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Mayevsky.
Explore the source record for details and available documents.
Traumatic brain injury (TBI) is known to be accompanied by an increase in intracranial pressure (ICP) and in some cases, by spontaneous generation of cortical spreading depression (CSD) cycles. However, the role of CSD in the pathophysiology of cerebral contusion is still unknown. A multiparametric monitoring assembly was placed on the right hemisphere of the rat brain to evaluate ICP, DC potential, extracellular K(+), cerebral blood flow (CBF), and electrocorticogram in 27 rats during 5 h. Fluid percussion brain injury (FPBI) with the magnitude of the impact 2.9, 3.3, 4.1, and 5.0 atmospheres was induced to the left parietal cortex in animal groups A, B, C, and D, respectively. A slow increase in ICP was evident, and was pronounced in group C and especially in group D, where four of nine animals died during the monitoring. At the end of the 5 h experiment, the mean ICP levels were 6.75 +/- 2.87, 8.40 +/- 2.70, 12.75 +/- 4.03, 29.56 +/- 9.25, and the mean total number of CSD cycles was 2.00 +/- 1.41, 4.29 +/- 4.23, 11.71 +/- 13.29, and 20.11 +/- 19.26 in groups A, B, C, and D, respectively. The maximal level of intensity of CSD cycle generation after FPBI was obtained in group D, where almost constant activity was maintained until the end of the experiment. A significant coefficient of correlation between ICP level and total number of CSD cycles was found for all ICP measurements (r = 0.47-0.63, p < 0.05, n = 27), however more significant (p < 0.001) was the coefficient during the period of monitoring between 2 and 4 h after FPBI. Our results suggest that numerous repeating CSD cycles are typical phenomena in moderate and especially severe forms of FPBI. The rising number of CSD cycles under condition of an ICP level >/=20 mm Hg may demonstrate, with high probability, the unfavorable development of TBI, caused by growing secondary hypoxic insult.
The brain of neurosurgical patients are exposed to various manipulations in the ICU or during surgery. Under such conditions brain O2 balance may become negative and as a result brain vitality and function will deteriorate. In order to evaluate brain vitality in real time it is important to measure more than one parameter. The multiparametric monitoring system used in our previous study to monitor comatose patients (Mayevsky et al., Brain Res. 740: 268-274, 1996) was changed into a "simplified" tissue spectroscope for real time monitoring of brain O2 balance. Mitochondrial function was evaluated by monitoring the NADH redox state by surface fluorometry. Microcirculatory blood flow was assessed by laser Doppler flowmetry. The combined optical probe was located on the surface of the brain during various neurosurgical procedures and the responses were recorded and presented in real time to the surgeon. A total of 32 patients were monitored during various procedures. The results could be summarized as follows: 1. Hypercapnia led to 3 different types of responses. In two patients the 'stealing' like event was recorded. In the other 7 patients the responses to high CO2 was not detectable. In the last group of 6 patients a clear CBF elevation was recorded with variable response of mitochondrial NADH. 2. Our monitoring device was able to evaluate the efficacy of the STA-MCA anastomosis during aneurysm surgery. 3. A significant correlation was recorded between CBF and NADH redox state during changes in blood pressure, papaverine injection, spontaneous drop in blood supply to the brain or during releasing of high ICP levels. We conclude that in order to evaluate the metabolic state of the brain during neurosurgical procedures it is necessary to monitor both CBF and mitochondrial NADH by using the tissue spectroscope.
The application of hyperbaric oxygenation (HBO2) has been recommended for correction of neurological injury in severely CO-poisoned patients. However, the mechanisms of HBO2 action on brain mitochondrial function under the circumstances is not yet understood completely. In the present study, the effect of HBO2 on the rat brain after CO exposure was evaluated by measuring the intramitochondrial NADH and its responses to anoxic test or repetitive induction spreading depression (SD) leading to brain activation. A unique monitoring system for bilateral monitoring of brain NADH redox state was used. Rats were exposed to 3000 ppm CO for 30 (group A) or 60 min (C). In groups B and D, after CO exposure, the rats were exposed to HBO2 (3 atm abs for 30 min). Following CO exposure in groups A and C, a definite decrease in the amplitude of the NADH response and significant increase in the number of waves of NADH was noted during induced cortical SD. Anoxic test in these two groups led to a significant decrease of maximum levels of NADH (reduction) at the end of observation. The amplitude, and the number of SD waves and magnitude of NADH deviation during anoxic test in group B after application of HBO2, was not significantly different from the values measured under the initial conditions. However, in group D, tendency of maintenance of the parameter's initial level was weaker or absent. The results obtained indicated that suppression of brain energy metabolism is a characteristic manifestation of CO poisoning in rats. Restoration of cerebral energy metabolism by adequate dosage of HBO2 may become an important factor for recovery of brain activities after CO poisoning.
Alcohol induces a decrease in cerebral blood flow (CBF) and metabolic rate, mitochondrial damage and other impairments in brain function and structure. Cortical spreading depression (CSD) is a phenomenon causing changes in ion homeostasis and raises energy demand, mitochondrial activity and CBF. It is of great interest to study the effect of ethanol on brain response under a challenge of increasing oxygen demand by inducing CSD. A special multisite assembly (MSA) was constructed to evaluate metabolic (mitochondrial NADH), hemodynamic (reflectance) and electrical (DC potential) activities from four parasagittally adjacently arranged areas of the cerebral cortex, continuously and simultaneously in vivo. Three CSD cycles were initiated every 30 min before and after ethanol or saline infusion over 4.5 h. During CSD amplitude changes of reflectance, NADH and DC potential as well as propagation rates and wave frequency were calculated. After ethanol infusion CSD showed a decrease in the negative shift of the DC potential, and alterations in the biphasic responses in reflectance, which may indicate alteration in blood volume: unclear responses in the initial vasoconstriction phase and a significant increase in the subsequent vasodilatation phase. The reduction in the amplitude of the NADH oxidation cycle may depict a decrease in energy production, which could also be indicated by a decline in wave frequency (prolonging the recovery phase of the CSD). The decrease in propagation rate indicates a decline in tissue excitability and in the CSD initiation mechanism induced by ethanol treatment.
Explore the source record for details and available documents.
Intracranial hypertension may develop in most patients exposed to traumatic head injury. In many cases, patients enduring elevated intracranial pressure (ICP) will incur morbidity or mortality. Several methods are used in animal models to investigate the influence of ICP elevation on physiological parameters. In this study, we developed a cisterna magna model by adding a mechanism for warming the mock cerebrospinal fluid (CSF) entering the cisterna space to a temperature of 37 degrees C and combined this method for ICP elevation with the multiparametric monitoring system (Multiprobe Assembly [MPA]). Using the MPA, we monitored, for the first time, mitochondrial NADH redox state as well as ionic homeostasis under elevated ICP in a rat model. In addition, we monitored cerebral blood flow (CBF) by laser Doppler flowmetry, ECoG (bipolar electrodes), and surface temperature. Blood pressure was measured in the cannulated femoral artery. The ICP (monitored by Camino probe) was elevated to 50-60 mm Hg for 13-15 min, followed by 2 h of recovery. The results show that CBF was decreased by 90%, while NADH was elevated by 80% as compared to the normoxic levels. Complete depolarization occurred as evidence by the decrease in extracellular Ca2+ and a significant increase in K+. All parameters recovered 10 min after reopening the cannula to the cisterna magna to air pressure. We conclude that ICP elevation through the cisterna magna infusion method, used simultaneously with multiparametric monitoring, supplies reliable information on the brain tissue metabolic state with intracranial hypertension in a rat model.
The effect of cortical spreading depression (CSD) on oxygen demand (extracellular K(+)), oxygen supply (cerebral blood flow - CBF) and oxygen balance (mitochondrial NADH) was studied by a special multiprobe assembly (MPA), during hypoxia and partial ischemia. The MPA was constructed and applied to monitor the CSD wave from its front line until complete recovery, continuously and simultaneously. CSD under hypoxia or partial ischemia led to an initial increase in NADH levels and a further decrease in CBF during the first phase of the CSD wave, indicating a decrease of tissue capability to compensate for an increase in oxygen demand. Furthermore, the special design of the MPA enabled identifying the close interrelation between oxygen demand, supply and balance during CSD propagation. In conclusion, brain oxygenation was shown to have a clear effect on tissue responses to CSD.
The multiparametric monitoring system was applied to study the effects of 2000 ppm carbon monoxide (CO) on brain functions in vivo in the aging rat. The vasodilatory (non hypoxic) effects of CO on CBF in normal adult rats, which were shown in concentrations of 1000-2000 ppm involved the effect of nitric oxide (NO). Energy metabolism was evaluated by optical monitoring of CBF and mitochondrial function by fluorometry of NADH. Ionic homeostasis was evaluated by monitoring the extracellular level of K(+) and H(+) and the DC steady potential. Seven aging rats (24 months) were exposed to 2000 ppm for 60 min and 120 min of recovery, while five control rats were exposed to air under the same conditions. A comparison between the CO group and the control group showed that the changes in CBF, NADH and light reflectance were not statistically significant while extracellular K(+) was elevated and tissue pH became more acidic. Thus, the typical CO induced increase in CBF, was not recorded in the aging rats. We concluded that the brain vasodilatory response to CO was not active in the aging rat, while the ionic homeostasis responses were similar to those found in the adult rat.
Explore the source record for details and available documents.
Age is a natural factor that has been found to significantly affect sensitivity to hyperbaric hyperoxia (HBO). Exposure to HBO may lead to damages in the energy metabolism of the brain cells. The aim of this study was to test the effect of HBO on the metabolic, hemodynamic and electrical activities in the newborn dog. The study was performed using one-day- to 70-day-old puppies. The puppies were placed in a pressure chamber. The pressure of pure O2 in the chamber was raised by 5 atmospheres (ATA, 75 psi = 6 ATA) within 10 min. The first biochemical change to take place during HBO was oxidation of mitochondrial NADH. The age of the puppy was found to affect the time to the initiation of seizures. In the puppies under the age of 24 days, the average time was 35.1 +/- 5.9 min. In the puppies of 24 days old and older, the average time was 5.1 +/- 0.8 min. In the younger puppies, there was a later occurrence of blood vessel contractions and a longer life span compared to the older puppies. The comparison between the puppies of different ages during exposure to HBO showed differences in the metabolic response, hemodynamic changes and electrical activity. These differences can partially explain the higher resistance in the younger puppies to HBO.
A variety of methods has been used in order to obtain a state of acute cerebral ischemia. Most of these methods suffered from drawbacks such as irreversible ischemia, difficult to obtain total ischemia and heart injury. The aim of this study was to develop a new method for induction of global or partial cerebral ischemia in the newborn dog at various post-natal ages. A multi-parameter monitoring system (MPA) measures the metabolic (mitochondria NADH oxidation/reduction state), hemodynamic (reflectance), ionic (extracellular potassium and calcium) and electrical changes (ECoG) continuously and simultaneously in the puppy's brain in vivo. A hole was made in the chest cavity, the two large arteries supplying blood to the brain, the brachiocephalic and the subclavian arteries (B + S) were isolated and occluded during the monitoring. In most of the animals, occlusion of these two arteries alone resulted in partial ischemia. For obtaining 100% ischemia, we occluded both the B + S arteries as well as the aortic arch. Immediately at the onset of ischemia, an increase (reduction) of NADH begins. During complete ischemia the average time until maximal increase was 4 min, compared to ischemia of up to 50% of the maximal reduction of the NADH where the average time was 1 min. After reperfusion of the brain, mitochondria recovery was very rapid and the average time until return of this parameter to its pre-ischemic level was 1.4 +/- 0.2 min. The ionic changes which occurred immediately upon the onset of ischemia were the accumulation of extracellular potassium ions was recorded. The rate of potassium ion accumulation was dependent on the severity of the ischemia (range 0.19 +/- 0.08-2.2 +/- 0.4 mM min-1). The increase in the extracellular potassium ion concentration occurs in two stages, an initial slow stage and a second rapid stage (13.0 +/- 1.8 mM). The results presented in this paper suggest and prove the usefulness of a new approach for global and partial ischemia in the newborn dogs. In addition, our results assess the brain metabolic, ionic, hemodynamic and electrical responses to brain ischemia in the puppies.
The main difference between newborn and adult brains is expressed in the relative resistance of the newborn brain to oxygen deprivation. The aim of the present study was to examine the effect of global ischemia in canine puppies of three different ages on the metabolic, ionic and electrical activity of the brain and to study the basic mechanisms underlying the relative resistance of the newborn brain in ischemic episode. The puppies were divided into three age groups. The young group included 0-6-day-old puppies (n = 16), the intermediate group included 7-19-day-old puppies (n = 21), and the 'adult' group included puppies aged 20 days or more (n = 17). Statistical analysis of the results led to the following conclusions: The younger the puppy, the longer is the time until the occurrence of the secondary reflectance increase SRI (13.0 +/- 1.9 min vs. 5.3 +/- 0.5 min). The younger the puppy, the longer the time until onset of potassium leakage from the cells (0.9 +/- 0.1 min vs. 0.35 +/- 0.05 min) and the lower the amount of potassium leakage (9.6 +/- 2.8 mM vs. 21.7 +/- 4.8 mM). The rate of pumping of the potassium ions into the cells during the recovery stage was higher in the oldest group (1.2 +/- 0.2 mM min-1 vs. 0.38 +/- 0.1 mM min-1). It was possible to speculate that in the young puppies there is uncoupling of the oxidative phosphorylation from respiration and as a result, there is a lower, if any, rate of ATP synthesis. It seems that the newborn brain is able to cope with a decrease in available energy for a longer period of time. This is apparently due to differences in membrane characteristics and an improved ability to retain ionic equilibrium across both sides of the membrane.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have developed the Brain Viability (BVA) and Brain Function (BFA) Analyzers for monitoring the following parameters from the human cerebral cortex cerebral blood flow: (CBF), NADH redox state, Electro corticography (ECoG), brain temperature, extracellular K+, DC potential and intracranial pressure (ICP). The BVA monitors the first 4 parameters only. The Brain viability probe (BVP) and Brain function multiprobe (BFM) were used during 11 operations and in 18 ICU patients, respectively. Preliminary results from the OR showed that 5 patients exhibited a typical increase in CBF in response to changes in end-tidal CO2 without a significant change in the NADH redox state. In 4 other patients no changes in CBF and NADH were observed. Two patients exhibited a "steeling response", i.e., a decrease in CBF and an increase in NADH. In 18 comatose patients monitored in the ICU, the ICP, CBF and ECoG were measured correctly in most patients, whereas NADH and K+ were more problematic. One patient exhibited a typical response, may be due to repeated cortical spreading depression cycles and an ischemic depolarization event. Continuous realtime multiparametric monitoring in neurosurgical patients is feasible and practical in the OR and the ICU. The information provided could be used as a diagnostic tool to guide the procedures or treatment given to the patients.
The aim of this study was to examine the inter-relation between the hemodynamic events, energy metabolism, extracellular potassium and electrical activity during the acute phase of transient ischemia in the gerbil brain. It has already been shown that partial ischemia in the gerbil brain causes changes in the blood flow, oxygen tension, electrical activity and potassium ion efflux. However, the description of the event during brain recovery from transient ischemia is not documented. In order to enable a better understanding of the pathophysiology during the ischemia as well as during reperfusion, we used the multiparametric assembly system. This system enables simultaneous and continuous monitoring of CBF, intra-mitochondrial NADH, extracellular potassium, DC potential and ECoG. Twenty anesthetized gerbils underwent reversible carotid artery occlusion procedure for 3-4 min. While monitoring the various parameters until complete recovery was reached, we found high correlation between the CBF and the NADH during occlusion as well as during the reperfusion period. However, CBF at the reperfusion period increased above the basal level while NADH returned to base line without an undershoot, suggesting that the mitochondrial need for oxygen necessary for the production of ATP is not the only factor influencing CBF during reperfusion. Furthermore, NADH returned to its normal level before extracellular potassium ion levels recovered to the baseline. This may suggest that ATP was no longer the limiting factor and ion pump activity became the factor determining and affecting the recovery processes.