Stimulation Of Contralateral Sciatic Nerve Research Articles

Correlation of intrinsic optical signal, cerebral blood flow, and evoked potentials during activation of rat somatosensory cortex

This study was undertaken to test the hypothesis that cerebral blood flow (CBF) and the intrinsic optical signal could be dissociated by altering adenosine receptor activity and to uncover the origin of the optic signal using a cranial window in the anesthetized rat. In anesthetized, ventilated, and temperature-controlled rats with closed cranial windows, the authors evaluated simultaneously the alterations in pial arteriolar diameter, intrinsic optical signals (690 nm), and somatosensory evoked potentials during cortical activation evoked by contralateral sciatic nerve stimulation (SNS). To dissociate the vascular and intrinsic signal, they topically applied the adenosine receptors antagonists theophylline (5 microM), which affects A1 and A2A receptors, and 8-cyclopentyl-1,3-dipropylxanthine (CPX, 1 microM), which blocks the A(1) receptor. The former interacts primarily with the vasculature whereas the latter influences the parenchyma exclusively. During 20 seconds of contralateral SNS, pial arterioles in the hindlimb somatosensory cortex dilated in a characteristic peak and shoulder pattern. As compared with mock cerebrospinal fluid alone, theophylline significantly (p<0.05) attenuated SNS-induced vasodilation (mean+/-standard deviation 8.1+/-2.5% vs 21.7+/-1.9%; 4 rats in each group). In contrast, CPX potentiated vasodilation significantly (p<0.05) during SNS (54.7+/-15.8% for the CPX group vs 20.1+/-1.9% for the controls; 5 rats in each group). The change in optical signal persisted after cessation of SNS in all the animals. Thus, the pattern of change of the optical signal was distinctly different from the pattern of changes in arteriolar diameter (which returned rapidly to baseline). Moreover, the optical signal during SNS was increased by 50% by theophylline and by almost 5-fold by CPX (p<0.05). The area of change of the intrinsic signal was also increased by the topical application of theophylline and CPX. The somatosensory evoked potential recordings revealed no significant changes after theophylline application, but CPX caused a small diminution of the N1 wave (p<0.01). The noncongruent temporal profiles of the changes in pial arteriolar diameter and optical signal, imaged at 690 nm, indicate that the optical signal at 690 nm is not related to CBF. Alteration of adenosine receptor activity independently changed cortical activity, as measured by the optical signal, and CBF, as determined by pial arteriolar diameter. Manipulation of the adenosine receptor activity during increased cortical activity confirmed the temporal dissociation of optical signal and CBF and provided further evidence for the role of adenosine in regulating CBF.

Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

Despite its wide consumption and well-documented psychoactive effects, little is known regarding the effects of caffeine, an adenosine receptor antagonist, on neurovascular coupling. In the present study, we evaluated the effects of caffeine on intracerebral arterioles in vitro and on the pial circulation in vivo during cortical activation induced by contralateral sciatic nerve stimulation (SNS). In our in vitro studies, we utilized isolated intracerebral arterioles to determine the effects of caffeine (10 or 50uM) on vasodilatation induced by extraluminal application of adenosine. Adenosine caused dose-dependent dilations. Pretreatment with caffeine alone, at either of the concentrations tested, had no effect on resting diameter. The higher concentration (50uM) of caffeine resulted in significant attenuation of adenosine-induced vasodilatation (p<0.05, n=5), whereas 10uM had no effect. We utilized reverse-phase HPLC to quantify in vivo CSF caffeine concentrations. Intravenous administration of 5 mg/kg caffeine led to CSF concentrations of approximately 3uM, whereas higher doses (10 and 40 mg/kg), resulted in CSF caffeine accumulations of more than 10 and 60uM, respectively (n=18). To study the effect of caffeine on neurovascular coupling, we created a close cranial window in anesthetized, ventilated and temperature-regulated rats. Pial arteriolar response to contralateral sciatic nerve stimulation (SNS) was then evaluated before and after intravenous administration of caffeine (5, 10, 20 30 & 40 mg/kg). Contralateral SNS resulted in a 23.8% increase in pial arteriolar diameter in the hindlimb sensory cortex under control conditions. Intravenous administration of caffeine at the lowest dose (5 mg/kg), equivalent to 2 cups of brewed coffee, had no effect on resting arteriolar diameter but slightly suppressed the arteriolar response to somatosensory stimulation. This trend, however, did not reach statistical significance. At all of the higher doses (10, 20, 30 & 40 mg/kg, i.v.), caffeine significantly attenuated the cerebral blood flow responses to contralateral SNS (Figure 1; p<0.05; n=6). Caffeine administration also significantly reduced resting arteriolar diameter. In contrast, hypercarbic vasodilatation was unaffected by caffeine at any of the doses tested. The results of the present study demonstrate that caffeine significantly reduces cerebrovascular responses to both adenosine and to somatosensory stimulation and supports a role of adenosine in the regulation of CBF during functional neuronal activity.

Effect of Caffeine on Cerebral Blood Flow Response to Somatosensory Stimulation

Despite caffeine's wide consumption and well-documented psychoactive effects, little is known regarding the effects of caffeine on neurovascular coupling. In the present study, we evaluated the effects of caffeine, an adenosine receptor antagonist, on intracerebral arterioles in vitro and subsequently, on the pial circulation in vivo during cortical activation induced by contralateral sciatic nerve stimulation (SNS). In our in vitro studies, we utilized isolated intracerebral arterioles to determine the effects of caffeine (10 or 50 micromol/L) on adenosine-induced vasodilatation. At the lower concentration, caffeine was without effect, but at the higher concentration, caffeine produced significant attenuation. In our in vivo studies, we determined the cerebrospinal fluid (CSF) caffeine concentrations at 15, 30, and 60 mins after intravenous administration of 5, 10 and 40 mg/kg. At the latter two concentrations, CSF levels exceeded 10 micromol/L. We then evaluated the pial arteriolar response during cortical activation caused by contralateral SNS after administering caffeine intravenously (0, 5, 10, 20 30, and 40 mg/kg). The pial circulation was observed through a closed cranial window in chloralose-anesthetized Sprague-Dawley rats. The contralateral sciatic nerve was isolated, positioned on silver electrodes and stimulated for 20 secs (0.20 V, 0.5 ms, and 5 Hz). Arteriolar diameter was quantified using an automated video dimension analyzer. Contralateral SNS resulted in a 23.8% +/-3.9% increase in pial arteriolar diameter in the hindlimb sensory cortex under control conditions. Intravenous administration of caffeine at the lowest dose studied (5 mg/kg) had no effect on either resting arteriolar diameter or SNS-induced vasodilatation. However, at higher doses (10, 20, 30, and 40 mg/kg, intravenously), caffeine significantly (P < 0.05; n = 6) attenuated both resting diameter and cerebral blood flow (CBF) responses to somatosensory stimulation. Intravenous administration of theophylline (10, 20, and 40 mg/kg), another adenosine receptor antagonist, also significantly reduced SNS-induced vasodilatation in a dose-dependent manner. Hypercarbic vasodilatation was unaffected by either caffeine or theophylline. The results of the present study show that caffeine significantly reduces cerebrovascular responses to both adenosine and to somatosensory stimulation and supports a role of adenosine in the regulation of CBF during functional neuronal activity.

Pial arteriole dilation during somatosensory stimulation is not mediated by an increase in CSF metabolites.

Pial arterioles supplying the hindlimb somatosensory cortex dilate in response to contralateral sciatic nerve stimulation. The mechanism of this pial vasodilation is not well understood. One possibility is that vasoactive metabolites released during brain activation may diffuse to subarachnoid cerebrospinal fluid (CSF) to dilate pial vessels. To test this hypothesis, we implanted closed cranial windows in rats and measured pial arteriolar dilation to sciatic nerve stimulation during constant rate superfusion of the pial surface with artificial CSF. We reason that flushing the pial surface with CSF should quickly dissipate vasoactive substances and prevent these substances from dilating pial arterioles. CSF flow (1 and 1.5 ml/min) significantly reduced pial arteriole dilation induced by 5% CO2 inhalation, but the same flow rates did not affect dilator responses to sciatic nerve stimulation. We conclude that brain-to-CSF diffusion of vasoactive metabolites does not play a significant role in the dilation of pial arterioles during somatosensory activity.

Effect of adenosine receptor blockade on pial arteriolar dilation during sciatic nerve stimulation.

In the present study, we report the effects of adenosine receptor antagonists on pial vasodilatation during contralateral sciatic nerve stimulation (SNS). The pial circulation was observed through a closed cranial window in alpha-chloralose-anesthetized rats. In artificial cerebrospinal fluid (CSF), SNS resulted in a 30.5 +/- 13.2% increase in pial arteriolar diameter in the hindlimb somatosensory cortex. Systemic administration of the selective adenosine A2A receptor antagonist, 4-(2-[7-amino-2-[2-furyl][3,2,4]triazolol[2,3-a][1,3,5]triazin-5-yl-amino] ethyl)phenol (ZM-241385), significantly (P < 0.05, n = 6) attenuated the SNS-induced vasodilatation. Systemic administration of 8-(p-sulfophenyl)theophylline (8SPT), a nonselective antagonist that is blood-brain barrier (BBB) impermeable, had no effect on vasodilatation to SNS. In contrast, systemic theophylline, which readily penetrates the BBB, nearly abolished the SNS-induced vasodilatation (P < 0.01; n = 7). Topical superfusion of 8SPT significantly (P < 0.01; n = 6) attenuated vasodilatation during SNS. Topical superfusion of 8- cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, significantly potentiated SNS-induced vasodilatation (P < 0.01; n > or = 5). Hypercarbic vasodilatation and somatosensory-evoked potentials were not affected by any of the compounds tested. Our findings suggest that luminal endothelial adenosine receptors are not involved in the arteriolar response to SNS, as demonstrated by a lack of effect with systemic 8SPT. Furthermore, the adenosine A2A receptor subtype appears to be involved in the dilator response to SNS. Finally, the neuromodulatory action of adenosine, via the A1 receptor subtype, significantly influences SNS-induced vasodilatation. Thus the present study provides further evidence for a role of adenosine in the regulation of CBF during somatosensory stimulation.

Jaw muscle response to stimulation of type II somatosensory afferents of limbs in the rat.

Convergence of various afferent inputs onto brainstem neurones may play an important role in the regulation of trigeminal motor activity. In particular, previous studies suggest that, besides sensory inputs arising from the orofacial region, extratrigeminal information may modulate jaw muscle function. In the present study the actions exerted on masseter and digastric muscles by the activation of somatosensory afferents coming from fore- and hind limbs were examined. The electromyographic activity (EMG) of masseter and digastric muscles was recorded in 20 anaesthetised rats, and EMG responses to single and paired electrical stimulation of common radial and sciatic nerves, at a threshold intensity for the activation of group II afferent fibres, were studied. The stimulation induced an excitatory response in both masseter and digastric muscles bilaterally. Ipsiand contralateral radial nerve stimulation evoked masseter responses at latencies of 13.8 +/- 2.4 ms and of 18.0 +/- 2.6 ms, respectively, and digastric responses 1.6 +/- 0.4 ms later. Ipsi- and contralateral sciatic nerve stimulation elicited masseter responses at latencies of 21.4 +/- 2.6 ms and of 23.3 +/- 2.0 ms, respectively, and digastric responses 2.0 +/- 0.2 ms later. The same masseter and digastric motor units were excited by both radial and sciatic nerve stimulation; this suggests a convergence of somatosensory inputs arising from fore- and hind limbs on the same pool of masseter and digastric motoneurones. Paired stimulation of the two nerves did not induce any summation of the responses; this finding suggests that the two inputs, reaching a common relay station, could give rise either to occlusion or to inhibitory interactions. Spinotrigeminal relationship evidenced in this study may be involved in the coordination of jaw and limb movements.

Release of segmental amino acid neurotransmitters in response to peripheral afferent and motor cortex stimulation: A pilot study

The role of amino acid (AA) neurotransmitters in the spinal cord has been primarily studied using in vitro preparations and histochemical methods. The technology necessary to estimate AA levels in an intact animal has only recently become available. Such an investigation could yield valuable information regarding the segmental neurochemical environment. We measured the release of AAs into the rabbit lumbar spinal cord in response to sciatic nerve and transcranial stimulation with stereotaxically placed microdialysis catheters. Samples were obtained periodically during 90 minutes of continuous stimulation of either the left or right sciatic nerve, or motor cortex. Quantification of γ-amino butyric acid (GABA), aspartate, glutamate, glycine, and taurine was performed using high pressure liquid chromatography (HPLC). Adequate neural excitation was verified by recording somatosensory evoked potentials (SSEPs) or corticomotor evoked potentials (CMEPs). Sensory activation at intensities sufficient to activate small and large diameter peripheral fibers of the ipsilateral (to the microdialysis probe) sciatic nerve produced a significant change only in segmental glycine levels. Contralateral sciatic nerve stimulation failed to evoke a significant elevation of AAs. In addition, a significant increase in the release of glycine and taurine was measured after 90 minutes of transcranial stimulation. SSEP and CMEP components repeatedly showed adequate activation of primary afferent, descending motor fiber pathways, and segmental interneuron pools during dialysis sampling. Our data are consistent with the hypothesis that suprasegmental influence over peripheral afferent and motor activity may be, in part, through these amino acid neurotransmitters in the rabbit lumbar spinal cord.

Role of adenosine in regulation of regional cerebral blood flow in sensory cortex

We have previously demonstrated that rat pial arterioles located on the somatosensory cortex dilated in response to contralateral sciatic nerve stimulation (SNS). We hypothesized that the vasodilation was mediated by adenosine, released as a result of somatosensory cortex activation. To test this hypothesis, we examined the effects of SNS (0.15-0.2 V, 5 ms, 5 Hz for 20 s) on pial arterioles under conditions of altered adenosine availability. Cerebrospinal fluid (CSF) adenosine was altered by perfusing mock CSF, under a cranial window in anesthetized rats, containing either an adenosine uptake competitor (dipyridamole or inosine) or an adenosine receptor blocker (theophylline). With CSF only, SNS caused pial arterioles (resting diam, 29 +/- 1 micron) to dilate by 38 +/- 10% (peak magnitude) for 32 +/- 2 s. Dipyridamole (10(-6) M) significantly (P less than 0.02) enhanced both the magnitude (to 62 +/- 12%) and duration (to 68 +/- 10 s) of the response. Similarly, inosine (10(-3) M) significantly (P less than 0.02) potentiated the vasodilative response from resting values of 27 +/- 5% and 34.8 +/- 4.1 s to 37 +/- 6% and 89.6 +/- 14.1 s. In contrast, theophylline (5 x 10(-5) M) significantly (P less than 0.001) attenuated arteriolar vasodilation from resting values of 38 +/- 5% and 29.3 +/- 1.2 s to 18 +/- 3% and 22.0 +/- 0.9 s. Neither dipyridamole nor theophylline had a significant effect on neuronal response (sensory-evoked response) recorded from the somatosensory cortex. These results suggest that adenosine is involved in the regulation of pial vasodilation during cerebral cortical activation.

The lateral vestibular nucleus is a very important site for depressant actions of benzodiazepines on the crossed extensor reflex

We have reported that the crossed extensor reflex (CER) in Wistar male chloralose-anesthetized rats is very susceptible to the depressive action of benzodiazepine derivatives. The present study was designed to elucidate a possible site for this action in the central nervous system. Since the reflex contraction of the femoral quadriceps muscle elicited by an electrical stimulation of contralateral sciatic nerve was little influenced by diazepam (DZ) (0.05-2 mg/kg i.v.) in the chronic spinal rat, it is very probable that DZ may act first on supraspinal structures. DZ (2.5 μg) injected into the 4th ventricle produced much more potent and rapid inhibition of the CER than injection into the lateral ventricle. To find the most sensitive site involved in the area close to the 4th ventricle, microinjections of DZ in doses of 1 and 25 ng into the lateral vestibular nucleus (LVN) ipsilateral to the testing muscle produced a dose-dependent reflex depression which was clearly antagonized by Ro 15-1788, a benzodiazepine antagonist. Injections of 100 ng of DZ into other areas, i.e., the contralateral LVN, other subcerebellar nuclei, the red nucleus and the substantia nigra, produced no effects on the CER. Furthermore, electrolytic lesions of the ipsilateral LVN decreased the CER, while an electrical conditioning stimulation of the same nucleus increased it.

EFFECTS OF SPECIFIC AND NON-SPECIFIC AFFERENT IMPULSES UPON NEURONAL ACTIVITY OF THE SOMATOSENSORY CORTEX IN CATS

EFFECTS OF SPECIFIC AND NON-SPECIFIC AFFERENT IMPULSES UPON NEURONAL ACTIVITY OF THE SOMATOSENSORY CORTEX IN CATS

Effects of different frequencies of stimulation of sciatic nerves on the patellar reflex.

The patellar reflex was recorded every 10 seconds in cats under high cervical spinal section. The effects of different frequencies of electrical stimulation on both the ipsilateral and contralateral sciatic nerves were studied. At frequencies of 1–10/sec., contralateral sciatic nerve stimulation produced a depression of the patellar reflex. Frequencies of 20–120/sec. produced augmentation of the reflex. Stimulation of the ipsilateral sciatic nerve, through the same range of frequencies, only produced a gradient depression of the patellar reflex. The effect of pentobarbital on these reflexes in the same type of high cervical spinal cat was noted. The effects of frequency of stimulation, as well as anesthetic used, must be considered in using this reflex preparation.