John G. Blackburn

Peripheral nerve fiber and spinal cord pathway contributions to the somatosensory evoked potential

Abstract In monkeys anesthetized with 70% N2O-30% O2, alterations in the configuration of the somatosensory evoked potential (SEP) were observed to follow specific spinal cord lesions. The SEPs were recorded in response to stimulation of the exposed superficial peroneal nerve after bilateral dorsal or anterolateral column transection, right or left hemisection, or central cord lesions. Stimulus intensities were sufficient to stimulate large nerve fibers or all nerve fibers. Small nerve fibers were selectively stimulated by blocking large fibers, using a combination of cooling and electrical polarization, while applying maximal stimulus intensities. The results indicate that large-diameter peripheral nerve fibers and the dorsal columns contribute primarily to early wave components (less than 40 ms). Small-diameter peripheral nerve fibers and the anterolateral columns appear to contribute primarily to later wave components (greater than 70 ms). Both large- and small-diameter peripheral nerve fibers and both dorsal and anterolateral columns appear to contribute to components with latencies between 35 and 70 ms.

The effects of interaction between large and small diameter fiber systems on the somatosensory evoked potential

The effect of interaction between large and small diameter fiber systems on the somatosensory evoked potential (SEP) was studied in anesthetized cats. Activation of large diameter fibers of the peroneal or radial nerves eliminates the late components of the SEP produced by stimulation of all fibers in the contralateral median or radial nerves. The inhibitory effects of a selective conditioning stimulus to the large diameter fibers of the peroneal nerve on the radial nerve evoked SEP was eliminated by bilateral transection of the dorsal column and spino-cervical tracts. However, interaction could still be obtained following transection when both large and small diameter fibers in the peroneal nerve were stimulated. The results of this study support the hypothesis that a correlation exists between activity in different fiber groups in afferent nerves, their conduction pathways through the cord, and the components of the cortical evoked potential.

Cadmium nephrotoxicity in human proximal tubule cell cultures

SummaryHuman proximal tubule kidney cells grown in a serum-free tissue culture medium were exposed to concentrations of CdCl2 in a range of 0.5 to 10μg/ml. Cells were observed from 1 to 20 d upon initiation of cadmium in the culture fluid. Both confluent and subconfluent populations of cells were treated and evaluated for cytotoxicity. Both populations exhibited a concentration-dependent toxicity to ionic cadmium. For cells treated with 2.0 to 10 μg/ml Cd, the decreases in cell numbers were largely irreversible. However, cells treated with Cd in a range of 0.5 to 1.0 μg/ml exhibited a partial recovery of cell number and control morphology. In this range, recovery was more efficient in the subconfluent cultures. Fine structural alterations in Cd-treated tubule cells included condensation of nuclear chromatin, loss of microvilli structure, disorganization of lateral membrane interdigitation, as well as decreased uptake of aminoglycoside antibiotics as evidenced by decreased numbers of myeloid bodies in these cells. The results of this study imply that use of a human proximal tubule culture system has potential in discerning structural and functional effects of cadmium as well as other nephrotoxic metals and compounds on the human kidney.

Effects of spinal cord lesions on somatic evoked potentials altered by interactions between afferent inputs.

In cats anesthetized with alpha-chloralose, somatic evoked potentials (SEP) were recorded in response to electrical stimulation of surgically isolated peripheral nerves. Selected surgical lesions were made at T9-L1 spinal cord and were histologically verified. Two stimulus magnitudes were used to activate peripheral nerves, one only exciting the large fibers and another exciting the small fibers as well. Control SEPs were recorded in response to stimulation of both large and small fibers of the radial nerve. The later components (latencies greater than 40 msec) of this SEP were suppressed when evoked 100 msec after application of a conditioning stimulus (CS) to the large fibers of either peroneal nerve. Bilateral transection of the dorsal columns and spinocervical tracts eliminates these effects. Increasing the CS intensity to include small diameter fibers again resulted in reduction of the later components of the SEP. This interaction was largely eliminated if the transection was extended to include mid-lateral cord tracts. These results suggest that the SEP can be influenced by small fiber afferent activity conducted in mid-ventrolateral spinal cord in the absence of the dorsal columns and spinocervical tracts. Alterations in the forelimb-evoked SEP by a conditioning hindlimb stimulus is a sensitive indicator of spinal cord integrity. This method may be used to assess whether low spinal injury spares ventrolateral columns.

Oxygen tension in the globus pallidus and neostriatum of unanesthetized rats during exposure to hyperbaric oxygen

Abstract Unanesthetized rats were exposed 1 h to 100% oxygen at 60 psig (5 atmospheres absolute). Utilizing platinum semimicroelectrodes, oxygen tension was recorded from the globus pallidus and the neostriatum. Oxygen tension increased from control values (room air at ambient pressure) during the exposure period in both experimental groups. In the globus pallidus, oxygen tension reached the first stable peak in an average of 27.8 min, whereas in the neostriatum the first stable peak was reached in an average of 3.0 min. The results of this study suggest a correlation between oxygen tension and pathologic changes observed in the basal ganglia.

An electrophysiological freeze fracture assessment of cadmium nephrotoxicity in vitro

SummaryHuman proximal tubule cell cultures exposed to doses of cadmium chloride (CdCl2) between 0.05 μg/ml and 0.5 μg/ml exhibited alterations in cell membrane structure and transport function. At these Cd concentrations, cell numbers were not significantly altered from control values in either nonreplicating confluent, or actively replicating subconfluent cultures. Transmission electron microscopy revealed few alterations in cultures treated with 0.05 μg/ml Cd. Tight junctions were intact; organelles and myeloid body formation appeared normal. Freeze fracture analysis confirmed the integrity of the tight junctions as well as increased numbers of vesicles or pits along the lateral cell membrane, indicating increased endocytotic activity. Cells exposed to 0.1 μg/ml Cd were characterized by decreased numbers of microvilli and inhibited myeloid body formation. Cd doses of 0.5 μg/ml elicited nuclear chromatin condensation, fragmented sealing strands in 5 to 10% of the tight junction profiles, sparse microvilli, and inhibited myeloid body formation. Electrophysiologic assessments of transport function by Ussing chamber analysis revealed decreases in transepithelial potentials for all three concentrations, with significant differences at Cd concentrations of 0.5 to 0.1 μg/ml. Cells treated with 0.5 μg/ml Cd also exhibited slight decreases in electrical resistance, consistent with the minimal fragmentation of sealing strands observed in freeze fracture replicas. Resistance in cultures treated with 0.1 or 0.05 μg/ml Cd remained within control values and indicated that drops in potential difference and short circuit current in these cells reflected true alterations in ion transport.

Cardiac Pacing under Hyperbaric Conditions

Temporary external pacemakers have been reported to fail under hyperbaric conditions. In this study we investigated cardiac pacing under hyperbaric conditions. Permanent hermetically sealed pacemakers were found to function well under hyperbaric conditions, while several models of temporary external pacemakers failed. The electrical characteristics of pacing leads did not change under hyperbaric conditions. External pacing under hyperbaric conditions may be accomplished safely by using a permanent pacemaker attached to the patients temporary external leads.

The effects of spinal cord injury on somatosensory evoked potentials produced by interactions between afferent pathways.

The purpose of the present study was to determine the utility of somatosensory evoked potentials (SEPs) produced by interaction between afferent pathways for spinal cord injury evaluation. Interaction was measured as alterations in SEP configuration compared to controls. Monkeys anesthetized with N2O were used. Stimulus intensities were sufficient to excite all nerve fibers. The conditioning stimulus (CS) was applied to the left peroneal nerve and test stimulus (TS) to the left radial nerve. CS-TS intervals were 100 msec in duration. SEPs were recorded from primary cortical receiving area for the forelimb. Different surgical lesions were made at spinal cord level T3-T4. Amplitudes of TS-produced-SEPs remained unchanged postlesion. CS-produced-SEPs were found to be dependent upon the integrity of anterolateral column pathways. Accentuated interaction was observed following dorsal column ablation. Interaction was slightly enhanced after left hemisection but diminished after right hemisection or central cord lesion. Interaction between spatially separate afferent inputs as measured by SEP alteration was determined to be a sensitive indicator of spinal cord injury.

Effects of temperature on the electrical activity of the hypothalamic feeding centers

Abstract The effects of body temperature on electrical activity of the hypothalamic feeding centers was studied in lightly anesthetized cats. The temperature of the preoptic area of the hypothalamus was correlated with changes in electroencephalographic activity. An increase in body temperature was followed by an increase in the electrical activity of the satiety center and a decrease in activity in the feeding center. There were no significant changes in the levels or utilization rates of blood glucose, indicating that a glucostatic component was not operating in the present study. The results of the present study provide electrophysiological support for the thermostatic theory of food intake regulation.

Far-field Potentials as a Method of Monitoring Acute and Chronic Spinal Cord Injury

Far-field potentials (FFPs) were studied in monkeys to determine the utility of such responses in evaluating acute and chronic spinal cord injury. Monkeys (Macaca fascicularis) were anesthetized with 70% N2O 30% O2, immobilized with pancuronium bromide, and maintained on a respirator. Spinal cord transections were made at level T3-T4 and included bilateral dorsal columns or anterolateral columns, right or left hemisection, or central cord lesions. Percutaneous stimulation of both posterior tibial nerves was performed at a frequency of 3 Hz using 3-4 mA for 0.3 msec duration. Potentials were recorded from chronically implanted epidural electrodes (right ear reference) through a 300-3,000 Hz band pass filter. Each far-field potential represents the average of 256 individual responses recorded for a duration of 25 msec before and after cord lesion for up to 8 weeks. Seven reproducible components in the far-field potential could be identified. Following dorsal column transection all components were reduced in amplitude. After anterolateral column transection only latencies were altered. Right or left hemisections caused both attenuation of component amplitudes and latency alteration. Central cord lesions resulted in no detectable amplitude or latency disturbances. Control records likewise showed no changes. No major alterations, following day 1 posttransection, were observed, attesting to the relative stability of far-field potentials over long periods of time. Far-field potentials therefore may be useful in monitoring spinal cord injury.