Sven G. Eliasson

Regional blood flow in resting and stimulated sciatic nerve of diabetic rats

The role of ischemia in the pathogenesis of diabetic peripheral neuropathy remains uncertain. We used the distribution of [14C]butanol to measure resting regional sciatic nerve blood flow in normal, anesthetized rats and in rats with acute experimental diabetes from streptozotocin administration. Regional flows in hind limb biceps femoris muscle and skin were simultaneously measured. In additional diabetic rats, these blood flows were compared in both limbs after proximal electrical stimulation of one sciatic trunk (10 shocks/s) for 15 min. One month after streptozotocin administration, 8 of 11 test rats were hyperglycemic. Resting nerve blood flow in the hyperglycemic rats--5.6 +/- 3.07 ml.min-1.100 g-1--was significantly less than that in the controls (9.4 +/- 3.9 ml.min-1.100 g-1, P = 0.002). Muscle blood flow was normal and skin blood flow decreased in these rats. Calculated tissue vascular resistances were elevated in all three tissues. Stimulation of one sciatic trunk in five other diabetic rats resulted in a stimulated nerve blood flow of 15.7 +/- 7.7 ml.min-1.100 g-1, and nerve blood flow in the resting control limb was 7.7 +/- 4.3 ml.min-1.100 g-1 (P = 0.009). Muscle blood flow increased approximately fourfold on the stimulated side but skin blood flow did not increase. Resting sciatic nerve blood flow is modestly decreased in acute streptozotocin-induced diabetes, but the neural blood vessels are still responsive to the increase in nerve metabolic activity associated with nerve stimulation.

Lipid synthesis in peripheral nerve from alloxan diabetic rats.

Decreased conduction velocity in the peripheral nerves of rats is noted after induction of diabetes. The slowing of nerve conduction is accompanied by a decrease in the in vitro incorporation of radioactive precursors into some of the myelin lipids isolated from nerve segments. Cerebroside synthesis is more depressed than that of any other fraction. A change in the type of cerebrosides synthesized is seen with a pronounced decrease in the rate of incorporation of saturated fatty acids.

Sciatic nerve function following hindlimb thermal injury

Peripheral neuropathy occurs in approximately 20% of patients with major burns and seriously impairs rehabilitation. We describe an experimental model which permits elevation of the tissue temperature in the region of the distal sciatic nerve trunk of rats at a reproducible rate to a predetermined level without inflicting concomitant major cutaneous injury. Radiofrequency current is delivered through parallel copper electrodes mounted in a chamber into which the limb has been inserted. In the present experiments, tissue temperature was arbitrarily elevated to 47 degrees C for 30 sec in 62 rats. There were 43 normal controls. The posterior tibial branch was the most intensively studied, as some of its conduction characteristics can be serially assessed percutaneously. Conduction block, which was apparently irreversible, was present in 67% of posterior tibials by 24 hr postinjury. In branches which were still excitable, prolongation of the absolute refractory period was the most consistent abnormality noted. Slowing of conduction, as evidenced by prolongation of inflection velocity or peak velocity, was never observed. However, this injury resulted in selective conduction failure of sural--but not of peroneal--fibers which conducted at 40 m/sec or greater. Fiber modality is an important determinant of the vulnerability to direct thermal injury of peripheral nerve in vivo.

Differential effects of in vitro heating on rat sciatic nerve branches and spinal nerve roots

Locally applied heat induces nerve conduction block. Conflicting observations have been made regarding the relation of fiber conduction velocity to heat sensitivity. This study utilized sciatic nerve branches and spinal nerve roots which were heated until a substantial conduction block occurred. The results indicated that sensory fibers conducting at greater than 40 m/s are more heat-sensitive than motor fibers of the same conduction velocity.

Potassium ion channel blockade restores conduction in heat-injured nerve and spinal nerve roots

Compound action potentials were recorded in vitro from rat peroneal and sural nerves and from dorsal and ventral roots of the cauda equina before and after radiofrequency heating of 5-mm-length segments of these nerves to 41 to 45 degrees C. The heating was continued for intervals sufficient to reduce response amplitude by 50%. Inflection velocity, potential duration at 1/2 peak height, and the proportion of conducting A alpha fibers were also measured. The topical application of 4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA) to the previously heated segments immediately following the radiofrequency injury completely or near-completely restored amplitude height to the preheat value in all experiments. A alpha sensory fibers were the most susceptible to the conduction block. Conduction in these fibers was also the most readily restored by the application of 4-AP or TEA. The effects of TEA, but not of 4-AP, could be reversed by saline or buffer washing. Topical application of verapamil and of magnesium or calcium ions had no discernible effect on heated nerves. We suggest that the mechanism of heat-induced conduction block may be similar to that from early demyelination or stretch injury. Further, motor and sensory A alpha fibers differ both in their vulnerability to heat and in their subsequent response to the application of potassium channel blockers.

The role of visual impulses in the control of eye muscle activity.

Abstract Eye movements were induced by electrical stimulation of anterior and posterior cortical eye fields and anterior and posterior brain stem sites in cats. Electromyographic recordings from the eye muscles were used to evaluate the interaction between the electrically induced activity and photic stimuli. Eye movements induced from the frontal cortex and the posterior portion of the brain stem were facilitated by photic stimulation. Eye movements induced from the posterior cortex and anterior brain stem were not affected. Optimal facilitation was obtained with a photic stimulus frequency of 10 per sec with no effect below 4 per sec and above 20 per sec. Changing the direction of the infalling light in the direction of the induced eye movement further facilitated the eye motor neuron discharge.

Effects of 4-aminopyridine on protein phosphorylation in heat-blocked peripheral nerve

The topical application of 4-aminopyridine (4-AP) reverses within 1-3 min the partial conduction block that results from heating 5-mm segments of rat posterior tibial, peroneal and sural nerves to 45 degrees C for several minutes. Nerves previously blocked in vitro or in vivo were incubated in vitro in the presence of [gamma-32P]ATP. The rate of phosphorylation of soluble nerve proteins that had entered the media was determined. Labeled proteins were separated electrophoretically and autoradiograms prepared. We found that 5 mM 4-AP increases the phosphorylation rate in heat-blocked nerve by approximately 50-fold. The process is calcium-dependent and is heat-labile. Soluble proteins with a molecular weight in the 53-55 kDa range are preferentially but not exclusively phosphorylated in the presence of 4-AP at levels effective in restoring conduction. The results suggest that the potassium channel blocker 4-AP may restore conduction by inducing changes in channel proteins.

Stimulation of thiamine triphosphate metabolism in nerve by cyclic guanosine 3′,5′-monophosphate

This paper reports that addition of cGMP results in an increase of the amount of32Pi incorporated into thiamine triphosphate in nerve roots and sympathetic trunks. The effect is present both at rest and during electrical stimulation. Other nucleotides were less effective. Theophylline increased the incorporation, possibly because of phosphodiesterase inhibition. A blocking effect of atropine was noted in sympathetic trunk preparations that contain ganglion cells.

Noncontusive segmental spinal cord injury using radiofrequency current.

OBJECTIVE To develop a nondisruptive model for the study of spinal cord injury. METHODS A 2-MHz radiofrequency heating chamber was mounted over the rat T13-L1 vertebral column via a short dorsal incision. Epidural temperature at chamber level was monitored via a small proximal laminotomy. Forty-three rats were studied using time-temperature heating regimens from 45 to 48.5 degrees C and 4 to 15 minutes. A blinded numerical hind limb impairment score (Neurologic Impairment Score) was determined at intervals up to 2 weeks after injury. Segmental spinal cord blood flow was measured using [14C]butanol tissue uptake in injured and control rats. RESULTS Above the injury threshold, increasing the time-temperature regimens was associated with a progressively worse Neurologic Impairment Score (r = 0.73-0.87 up to 24 hours after injury). Cord blood flow was unchanged at 2 hours but was 44% depressed at the injury level 6 hours after injury (p < 0.01). Histologically, injury extended minimally beyond the injured segment. Vascular thrombosis was not seen. CONCLUSION This comparatively noninvasive model does not mechanically disrupt cord components and results in progressive neurologic impairment that correlates with the time-temperature regimen used for injury. It should be useful in identifying secondary phenomena that worsen functional status after cord trauma.