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J Appl Physiol 86: 1490-1496, 1999;
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Vol. 86, Issue 5, 1490-1496, May 1999

Oxygenation of the cat primary visual cortex

Lissa B. Padnick1, Robert A. Linsenmeier1,3,4, and Thomas K. Goldstick1,2,3,4

Departments of 1 Biomedical Engineering, 2 Chemical Engineering, and 3 Neurobiology and Physiology, and 4 Institute for Neuroscience, Northwestern University, Evanston, Illinois 60208-3107


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Tissue PO2 was measured in the primary visual cortex of anesthetized, artificially ventilated normovolemic cats to examine tissue oxygenation with respect to depth. The method utilized 1) a chamber designed to maintain cerebrospinal fluid pressure and prevent ambient PO2 from influencing the brain, 2) a microelectrode capable of recording electrical activity as well as local PO2, and 3) recordings primarily during electrode withdrawal from the cortex rather than during penetrations. Local peaks in the PO2 profiles were consistent with the presence of numerous vessels. Excluding the superficial 200 µm of the cortex, in which the ambient PO2 may have influenced tissue PO2, there was a slight decrease (4.9 Torr/mm cortex) in PO2 as a function of depth. After all depths and cats were weighted equally, the average PO2 in six cats was 12.8 Torr, with approximately one-half of the values being <= 10 Torr. The kurtosis of the PO2 histogram, with all depths and cats weighted equally, was 3.61, and the skewness was 1.70.

intracortical oxygen tension; brain


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

NEURAL TISSUE IS EXTREMELY vulnerable to hypoxic insult. Information concerning local brain PO2 may further the understanding of brain metabolism and may lead to treatments that minimize ischemic damage.

A number of investigators have studied oxygenation of the cerebral cortex and have obtained two different results. In some studies, cortical PO2 displayed steep PO2 gradients that resulted in high local variability in PO2 and large regions of near-zero PO2. Overall, there was a trend of decreasing PO2 with depth in the cat (21, 29), gerbil (22), and rat (7). The extensive regions of zero PO2 and the steep decrease in PO2 with depth are surprising considering that the cortex is richly vascularized. Average capillary spacing in the feline cortex has been reported to be as low as 25 µm (24) and can be calculated from published histological data (5) to be ~30 µm. In other studies, there was a less drastic decrease of PO2 with depth, and local PO2 maxima were found throughout the cortex. These local maxima represent oxygen sources, interpreted as cortical vessels. This type of PO2 depth profile has been observed in the rabbit (8), rat (16), guinea pig (16, 17), and cat (15).

The purpose of the present study was to reexamine PO2 depth profiles in the cat visual cortex by using 1) a chamber designed to maintain cerebrospinal fluid (CSF) pressure and prevent ambient PO2 from influencing the brain, 2) a microelectrode capable of recording electrical activity as well as PO2, and 3) a different protocol from standard penetrations for depth recordings.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Animal preparation. Six conditioned adult cats were used in this study. Under thiamylal sodium or pentothal sodium anesthesia, the two saphenous veins and one femoral artery were cannulated for drug delivery and blood pressure monitoring, respectively. A tracheotomy was also performed to allow for artificial respiration. The animal was then placed in a stereotaxic device (David Kopf, Tujunga, CA) inside a Faraday cage, and head surgery was performed.

Semisterile conditions were maintained. A sterile operating room was not used, but the instruments and the parts of the chamber that came into direct contact with the skull, the dura, the brain, or the artificial CSF (aCSF) were sterilized by heat or chemical (Metricide 28, Metrex Research, Parker, CO) means. These pieces were rinsed with boiled, distilled water on the morning of the experiment. Pyrogenesis did not occur.

An incision was made along the midline of the scalp, and the underlying temporalis muscle group was resected. A 0.75-cm-diameter hole was trephined 2 mm posterior and 3 mm lateral from lateral/anterior-posterior zero. This was directly above the primary visual cortex (area 17) (28). A small section of dura was removed with the aid of a microhook and a no. 11 scalpel blade. Initially, during surgery, the animal was given 100 mg of urethan intravenously every 15 min until the loading dose of 200 mg/kg had been administered. Paralysis was induced with rapid intravenous infusion of gallamine triethiodide just before the dura was cut, and artificial ventilation was initiated. This allowed PCO2 to be lowered transiently to cause vessel constriction and minimize brain pulsations. After completion of surgery, the animal was maintained on urethan anesthesia (~25 mg · kg-1 · h-1). Gallamine infusions (10 mg · kg-1 · h-1) were used to maintain paralysis. The animal was artificially ventilated at a rate and volume suitable for maintaining blood-gas values in a normal range (i.e., arterial PO2 >90 Torr, arterial PCO2 ~30 Torr; 7.35 < pH < 7.45).

A Plexiglas chamber, ~16 mm in diameter, was attached to the skull with dental acrylic (Bozworth Coralite Duz-All, Skokie, IL), and a Plexiglas plate with an electrode guide tube was lowered to complete the chamber. An O-ring between the chamber and the top plate ensured a proper seal. The chamber was then filled with an aCSF through the needle ports implanted in the side (Fig. 1). The electrode was inserted through the guide tube into the fluid above the brain and attached to a Kopf hydraulic microdrive, allowing fine control of the electrode depth. A silicone rubber cylinder (~7 mm in diameter, ~15 mm in height), molded to have a hole running through it, sealed the electrode to the electrode guide tube. The flexible nature of the silicone rubber allowed the seal to be formed and preserved during electrode movement. Figure 1 shows the setup in its entirety.


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  		Fig. 1.   Schematic of experimental setup.

After the chamber was filled with air-saturated aCSF, the chamber ports were closed and the fluid was allowed to equilibrate with the brain surface for several hours. The PO2 and PCO2 of the aCSF, close to the cortical surface, were assumed to be near natural CSF values. The steepness of the PO2 gradient near the cortical surface was used as an indicator of the degree of established equilibrium. After a few hours, the average PO2 across all cats in the 100 µm above the cortical surface was 27.4 ± 10.4 Torr. This was not significantly different from the average PO2 of the first 50 µm of the cortex (27.5 ± 12.9 Torr). The PCO2 and pH of the chamber were not monitored. There was negligible CO2 in the chamber fluid initially, and the aCSF was buffered independently of CO2. The initial pH of the HEPES-buffered fluid was 7.4. The pressure within the sealed chamber was assumed to regulate to normal CSF pressure.

Electrodes. Recessed, polarographic, double-barreled oxygen microelectrodes were constructed according to the method described by Linsenmeier and Yancey (14). The oxygen-sensing barrel consisted of a gold cathode, polarized at a constant voltage (-0.7 V) with respect to an Ag-AgCl reference. The second barrel was a saline-filled voltage electrode to make extracellular electrical recordings of the flash visual-evoked potential (F-VEP). Overall tip diameters ranged from 5 to 8 µm, with a cathode diameter of 1-2 µm. The electrode was calibrated in a saline-filled tonometer at 37°C by bubbling it with gases of known PO2. The oxygen content of the calibration gases was 4, 8, and 21% in earlier experiments and 0, 4, and 8% in later experiments to better match the low PO2 values observed in the brain. The electrodes used in these experiments had currents that were linear with the PO2 at the electrode tip. The sensitivity of the electrodes ranged from 3.6 × 10-14 to 5.6 × 10-13 A/Torr.

Stimuli. For F-VEP recording, a light diffuser was placed ~2 cm in front of the eye, and a fiber-optic bundle was positioned 1-2 cm behind the diffuser to uniformly illuminate the retina. Light stimuli for F-VEPs were produced by a tungsten iodide H1 automobile headlamp bulb, which had a maximum illumination of 9.4 [equivalent log quanta (555 nm)]/(degree2/s). The light source was contained in an optical bench located outside of the Faraday cage and brought to the cat via a fiber-optic bundle. A neutral-density wedge filter was used to attenuate the light source; a 2 log unit attenuation was generally used. A computer-driven timer (A-65 Timer/Stimulator, Winston Electronics, San Francisco, CA), which controlled the light shutter (ST-2 shutter driver, Winston Electronics; Uniblitz shutter, Vincent Associates, Rochester, NY), was programmed to give a 100-ms flash every 0.5 s for 25 s. The first four responses were not included in signal averaging, so the number of responses averaged for each F-VEP was 46.

Data collection. Oxygen currents were measured with a picoammeter (model 614, Keithley Instruments, Cleveland, OH), and the F-VEP was recorded with a unity gain amplifier (World Precision Instruments, New Haven, CT) followed by an oscilloscope (model 5111A, Tektronix, Beaverton, OR). All voltage and oxygen responses were recorded on a personal computer (486 processor) and/or a frequency modulation tape. The F-VEPs were acquired at 200 Hz. Oxygen signals were acquired at 20 Hz, but groups of 10 successive points were averaged for noise reduction, effectively reducing the sampling frequency to 2 Hz. A fast Fourier transform of the data digitized at 20 Hz revealed that >99% of the power was at frequencies <1 Hz. Therefore, a negligible amount of information was lost by reducing the data to 2 Hz.

After the electrode was inserted into the chamber fluid, a consistent surface F-VEP was identified. The electrode was lowered until the brain surface was indicated by a negative-going transient in the voltage trace of the electrode. The cortex was then penetrated in 3-µm steps. Tapping the electrode holder every two steps facilitated penetration. After the desired electrode depth was reached, the electrode was withdrawn at a rate of 2 µm/s while PO2 was continuously recorded. If electrophysiological (F-VEP) (23) and oxygen signals did not indicate a clean penetration, it was inferred that tissue dimpling, rather than penetration, had occurred, and the electrode was rapidly withdrawn without recording the PO2 profile. In a satisfactory penetration, the PO2 was nonzero in most, although not necessarily all, locations.

Data analysis. Recorded picoammeter oxygen currents were converted to PO2 by using pre- and postexperiment electrode calibrations. The current corresponding to 0 Torr was taken to be the lowest current recorded from the animal. A postexperiment calibration of the electrode was performed whenever possible to confirm the slope and the zero point of the electrode. In the event of a discrepancy between the in vivo low point and the postexperiment calibration zero (always <0.5 pA), the in vivo zero point was used.

Average PO2 was determined for each location during electrode penetration by averaging 30 s of measurement while the electrode was stationary. For withdrawal recordings, the average PO2 in each 50-µm interval was determined by averaging all data recorded in the interval.

Statistics. Statistical significance was determined by a paired or unpaired Student's t-test, as specified in RESULTS. A P value of <0.05 was used as the criterion for statistical significance.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The F-VEP. The electrophysiological response of the visual cortex to a diffuse light flash, the F-VEP, was monitored throughout the experiment. The F-VEP was used as an indication of electrode penetration and of cortex viability. Consistent surface components among cats were identified at ~100, 125, and 200 ms. These components were named according to their polarity in the surface recording (i.e., positive component at 100 ms is named P100). The most notable change in the waveform with electrode depth was the inversion (between 50 and 300 µm) and subsequent increase in amplitude of P200. A typical F-VEP depth profile is shown in Fig. 2. To the best of our knowledge, there have been no other good measurements of cat intracortical F-VEPs. Because major features of the waveform consistently changed with depth between cats, we interpret these responses as normal. A more complete description of the F-VEP results has been published elsewhere (23).


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  		Fig. 2.   Flash visual-evoked potential depth profile obtained from cat 172. Consistent surface components (P100, N125, and P200) are identified in surface recording. Dotted lines are for reference to emphasize how these components changed with depth. Stimulus used to evoke the response was a 100-ms diffuse light flash initiated at time 0. Each trace represents average of 92 responses.

Cortical oxygenation during electrode penetration. After an electrode advancement of 50 µm, a region of cortex was often found to have a PO2 near zero. After 2-5 min, fluctuations appeared, usually accompanied by an increase in the time-average local PO2. Figure 3 shows several examples of this occurrence at a variety of recording depths and baseline PO2 values in a single penetration. The peak-to-peak magnitude of these fluctuations ranged from ~1 to 5 Torr. Performing fast Fourier transforms on the data containing the temporal PO2 fluctuations revealed that there were large frequency components from 1 to 8 cycles/min and at 22.2 and 44.4 cycles/min (Fig. 3B).


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  		Fig. 3.   A: PO2 recordings during and after several 50-µm electrode advancements. Arrows indicate time of penetration, and horizontal bar represents 2 min. Depth, indicated on each trace, is depth of recording after electrode advancement. Increase in noise often occurring at time of penetration is an artifact of mechanical motion of electrode, and oscillations around 0 result from tape wobble on data redigitization. Redigitized data presented in this figure are used for illustration purposes only and were not used in any analyses. B: average fast Fourier transform (FFT) of PO2 data for 1 penetration (cat 192) spanning entire thickness of cortex. Data were recorded while electrode was stationary. Ninety-second recordings were collected every 50 µm for 2,000 µm after PO2 had recovered from transient decrease after each electrode advancement. Analyzed data were collected directly into a computer file and, therefore, do not contain redigitization artifact observed in A. For each file, best fitting quadratic function was subtracted from original data to remove any 0 cycles/min component and slow drift, and then FFT was obtained.

Figure 4 illustrates two PO2 profiles obtained during electrode penetration from different cats. A penetration through the full thickness of the cortex (~2 mm), in which PO2 was allowed to stabilize at each depth, took 3-4 h. Consequently, most profiles were obtained by penetrating more quickly and collecting data during electrode withdrawal.


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  		Fig. 4.   PO2 profiles through visual cortex during penetration for 2 cats [cat 191 (A) and cat 192 (B)]. Each point represents PO2 averaged for 30 s after a 50-µm penetration. PO2 was allowed to stabilize at indicated depth (as illustrated in Fig. 3) before data were recorded.

Cortical oxygenation during electrode withdrawal. Figure 5 shows several PO2 profiles obtained during electrode withdrawal accompanied by the corresponding PO2 frequency histograms. The PO2 measurements from the electrode penetration preceding one withdrawal, shown in the top trace, are indicated by solid circles. Generally, there was good agreement between the data obtained during electrode penetration and withdrawal. For cases in which two data sets (average PO2 during penetration and average PO2 during withdrawal) were available, they were not significantly different. Individual profiles did not show any indication of a drastic, sustained decrease in PO2 at deeper cortical locations. There may have been a small oxygen supply to the superficial cortex from the aCSF in some of the profiles, but this appeared to supply no more than ~100 µm of tissue. Numerous oxygen sources, appearing as local maxima in PO2 depth profiles, were observed throughout the entire cortex. These oxygen sources are interpreted as being vessels, although the distance from the electrode tip to the vessel and the PO2 within that vessel cannot be determined from these types of measurements.


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  		Fig. 5.   Left: corresponding PO2 histogram for each profile with individual profile mean. Right: several PO2 profiles obtained during electrode withdrawal from cat primary visual cortex. Top two profiles were recorded from same cat (cat 191), and bottom two were recorded from different cats (cats 192 and 172, respectively). Top trace shows PO2 measurements recorded during corresponding electrode penetration (). Zero is location of cortical surface.

The average PO2 was computed over each 50-µm interval in each profile (15 profiles in 6 cats). These values were used to construct the average profile of cortical PO2 in Fig. 6. The variation in the number of cats included at each depth reflects the difficulty of routinely obtaining clean penetrations that traversed the entire thickness of the cortex. Excluding the superficial 200 µm of the cortex where aCSF PO2 may have influenced tissue PO2, there was a shallow, but significant, gradient (-4.9 Torr/mm cortex) in cortical PO2 as a function of depth.


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  		Fig. 6.   Average PO2 within 50-µm intervals as a function of depth computed from profiles recorded during electrode withdrawal. Error bars represent 1 SE of mean, and n is no. of cats contributing to each section of graph. The point representing average for 1,950-2,000 µm is from 1 animal.

Averaging each 50-µm interval, as in Fig. 6, obscures the range of PO2 observed, and it does not give statistics that can be compared with previous work. Consequently, PO2 frequency histograms were compiled from all of the data in two different ways. Each data point from withdrawal profiles was weighted equally, regardless of the number of profiles per cat or the length of the profile (Fig. 7A). The mean of this distribution was 14.9 Torr (n = 17,977 points). The kurtosis and skewness of the histogram were 2.56 and 1.36, respectively. This method gives more weight to shallow depths and to cats in which more profiles were obtained. To avoid this problem, the data were also compiled in such a manner as to weight each depth and each cat equally (Fig. 7B). For each individual profile, a histogram of the points within each 50-µm interval was computed. These histograms were then grouped by cat and used to obtain an average histogram over all profiles for each depth interval within each cat. Those histograms for each cat at a specific depth interval were then averaged over all cats to weight each cat, from which data were collected, equally at each depth interval. Finally, the average histograms for each depth interval were averaged to obtain the grand histogram shown in Fig. 7B. Therefore, in Fig. 7B, the results from each cat, from which data were collected in a particular depth interval, were weighted equally. In addition, each depth interval was weighted equally to obtain the grand histogram. The mean of this distribution was 12.8 Torr. The kurtosis and skewness of this histogram were 3.61 and 1.70, respectively. The long tail on both distributions above 25 Torr corresponds to peaks in PO2, presumably near vessels. Similar statistics have been reported previously in a gerbil cortical PO2 study (3). In mature animals, the mean PO2, skewness, and kurtosis were 14.0 Torr, 0.996, and 3.32, respectively (3).


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  		Fig. 7.   A: PO2 histogram compiled by weighting all data points equally, regardless of recording depth or cat. Average PO2 was 14.9 Torr, and 49.6% of the points were <10 Torr. B: histogram representing frequency distribution of PO2 values for visual cortex, weighting data from each cat and each depth equally. Average PO2 was 12.8 Torr, and 59.1% of the values were <10 Torr. First bin in each histogram represents PO2 values between 0 and 2 Torr.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Cortical oxygenation measured during electrode penetration. The decrease in tissue PO2 and absence of spontaneous fluctuations just after microelectrode advancement (Fig. 3) may have been due to vasospasm or compression of the brain by the electrode. Spontaneous fluctuations in tissue oxygenation have previously been observed in neural tissue, and they are regarded as normal. Previous work has shown tissue oxygen fluctuations at a rate of 3.6-10.2 cycles/min in the rabbit (19), 10-12 cycles/min in unanesthetized, unrestrained cats (11), 3-8 cycles/min in barbiturate-anesthetized cats (11), and 6 cycles/min in humans (4). Similar fluctuations in rat cerebral blood flow (10, 12) and cat retinal PO2 (2) have also been observed. The present study is in good agreement with the above-mentioned work, finding PO2 fluctuations with frequencies in the range of 1-8 cycles/min. The faster frequency components in the present work at 22.2 and 44.4 cycles/min are the first and second harmonics of the respiratory frequency, respectively. Manil et al. (19) also observed fluctuations with a frequency of 21.6 cycles/min, which is presumed to have been the respiratory frequency.

The temporary disappearance of spontaneous PO2 fluctuations with electrode advancement, in the present study, indicates that care must be taken to allow for local area recovery during penetration profiles. This phenomenon may explain, in part, why some studies have shown a pronounced decrease in PO2 with depth (7, 21, 22, 29).

Cortical oxygenation measured during electrode withdrawal. PO2 profiles were recorded in minimally disturbed tissue in which surface PO2 and CSF pressure were probably close to normal and which produced responses to visual stimulation. It was more feasible to record during electrode withdrawal rather than penetration because it took several hours to traverse the cortex during penetration if time was allowed for recovery at each location. Recovery time did not seem necessary during electrode withdrawal because relatively rapid electrode withdrawal produced profiles that were similar to the carefully recorded penetration profiles when they were examined together (Fig. 5, top plot).

Many individual cortical PO2 depth profiles had distinct peaks in PO2 as close together as 25-30 µm. Similar spacing of cortical vessels has been observed in previous histological studies (5, 24). More often, the spacing of PO2 peaks was greater but not as large as others have found previously from penetration profiles (20). There was little effect of depth on cortical PO2 deeper than ~100-200 µm, and adjacent 200-µm-thick regions were not significantly different from one another.

Comparison of mean cortical PO2 among studies. Some features of the present study differ from previous cortical oxygenation studies. As a result, the mean cortical PO2 obtained here is lower than previously published averages for the cat (1, 13, 15, 18, 21, 29) by ~10-15 Torr. Several possible reasons for this difference can be considered.

The present study is the first to obtain PO2 depth profiles of the cortex during electrode withdrawal rather than during electrode penetration. It is unclear whether this would affect the mean cortical PO2 because our penetration and withdrawal data were in good agreement when PO2 levels were allowed to recover after electrode advancement (Fig. 5, top trace). Corresponding penetration and withdrawal profiles were not significantly different from one another in mean PO2.

The sealed, physiologically regulated chamber surrounding the skull hole allowed aCSF pressure and composition to be regulated by the cortex, while minimizing oxygen diffusion from the atmosphere. No brain edema or hemorrhaging was observed during the course of the experiments. In addition, the chamber fluid PO2 within the first 100 µm of the brain was not significantly different from the PO2 of the superficial-most 50 µm of the cortex. Feng et al. (7) demonstrated significant differences in an open- vs. closed-skull preparation in the rat. They concluded that diffusion of ambient oxygen from the surface can influence cortical PO2 to depths of 400 µm. In addition, opening the skull affected blood flow as deep as 1,000 µm. The mean cortical PO2 was ~28.3 Torr in the open preparation and ~19.8 Torr in the closed preparation (7).

In addition to preparation details, anesthetics may play a role in the observed differences. In five of the six previous cat studies, a barbiturate anesthetic was used during PO2 measurements (1, 13, 15, 21, 29). Fentanyl was used as the anesthetic in the sixth study (18). It is known that barbiturate anesthesia depresses cortical oxygen consumption and cerebral blood flow by a factor of two (27). In the present study, PO2 measurements were collected only under urethan anesthesia. Urethan is often the preferred anesthetic for neural recordings because it produces sufficient anesthesia and analgesia without interfering with normal central nervous system function (9).

When all depths and all cats were weighted equally, average cortical PO2 was 12.8 Torr (weighted average). The value was slightly higher at 14.9 Torr when all data points were weighted equally, regardless of depth or cat (point average). The skewness of the weighted distribution (1.70) was greater than that of the point distribution (1.36). The kurtosis of the weighted distribution and that of the point distribution were approximately equal at 3.61 and 2.56, respectively. Weighting the data properly, therefore, resulted in tissue PO2 histograms that were shifted to the left. Some previous studies contained a different number of profiles between cats, and not all of these profiles were measured over the same cortical depths (21, 29).

The combined effects of differing anesthetics, ambient PO2, unregulated CSF pressure, and calculation methods may explain the discrepancy in mean cortical PO2 between the present and previous studies (1, 13, 15, 18, 21, 29). These effects may also influence the results of studies performed in other species. The reported ranges of mean cortical PO2 are 12.9-28.3 Torr in the rat (6, 7, 25, 26), 14.0-35.4 Torr in the gerbil (3, 22), and 9.0-24.5 Torr in the rabbit (8, 27).

It is important that cortical PO2 measurements represent undisturbed tissue PO2 values. An effort was made in the present study to preserve the natural physiological condition of the tissue. Also, this is the first time that cortical electrophysiology has been used to assess electrode penetration. The measurements of the present study provide an accurate and detailed look at the depth distribution of oxygen in the visual cortex. Two different trends in PO2 distribution with depth have been observed previously. The first is a sharp PO2 decrease over the superficial cortex followed by a sustained low PO2 (7, 21, 22, 29). The second trend consists of a less drastic PO2 decline and has local PO2 maxima distributed throughout the cortex (8, 15-17). These maxima represent oxygen sources and are interpreted as vessels. In the present study, the second of the two trends was observed. To the best of our knowledge, the PO2 depth profiles presented here have greater spatial detail than those previously published.

From the measurements obtained in this study, we conclude that the average cortical PO2 may not be representative of cortical oxygenation. This is indicated by the large spatial variation in tissue PO2 and the large skewness of the PO2 frequency histogram (Fig. 7B). This may be important in the comparison of the cortex during normal and pathological states. By using the present method, it would be relatively simple to examine cortical oxygenation under a variety of altered physiological conditions (i.e., hyper-/hypoxia, hyper-/hypocapnia, hyper-/hypoglycemia) that are relevant to pathological conditions such as compromised cerebral blood flow and diabetes.


    ACKNOWLEDGEMENTS

We thank Jameel Ahmed, Monique McRipley, and Jennifer Kang for assistance during experiments and Dr. David Ferster for advice regarding animal preparation and useful discussion.


    FOOTNOTES

This work was supported by National Eye Institute Grant EY-05034.

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Address for reprint requests and other correspondence: R. A. Linsenmeier, Northwestern Univ., Dept. of Biomedical Engineering, 2145 Sheridan Rd., Evanston, IL 60208-3107 (E-mail: r-linsenmeier{at}nwu.edu).

Received 27 January 1998; accepted in final form 6 January 1999.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

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14.   Linsenmeier, R. A., and C. Yancey. Improved fabrication of double-barreled recessed cathode O2 microelectrodes. J. Appl. Physiol. 63: 2554-2557, 1987[Abstract/Free Full Text].

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J APPL PHYSIOL 86(5):1490-1496
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