Quantitative analysis of herpes simplex virus in cranial nerve ganglia

A susceptible individual exposed to herpes simplex virus (HSV) will develop latent infection in multiple cranial nerve ganglia. There are a few quantitative studies of the viral load within the trigeminal ganglion, but none that investigate other cranial nerve ganglia. In this study, human trigeminal, geniculate, vestibular (Scarpa's) and cochlear (spiral) ganglia were obtained from willed body donors. Real time quantitative polymerase chain reaction (PCR) analysis of the HSV DNA polymerase gene was performed on ipsilateral ganglion sets from the same individual. Viral load, expressed as HSV genomes per 105 cells, was significantly greater in the vestibular ganglion (mean +/- SD, 176705 +/- 255916) than in the geniculate (9948 +/- 22066), cochlear (3527 +/- 9360), or trigeminal (2017 +/- 5578) ganglia. There was not a significant correlation among ganglia from the same individual. The results support the hypothesis that neuronal subpopulations have variable susceptibility to HSV infection.     

乙状窦前和乙状窦后入路微创显露膝状神经节的虚拟现实比较

目的：通过虚拟现实技术比较乙状窦前和乙状窦后入路微创显露膝状神经节的显微解剖特征。方法对15例尸体头颅行M RI和C T扫描,将影像数据输入虚拟现实系统,构建颞骨三维解剖模型,在颅盖和颅底选择骨性标志点勾勒乙状窦前和乙状窦后入路显露膝状神经节的手术路径。观察两种路径的解剖结构空间形态和顺序,测量解剖组织体积,采用配对 t检验进行比较分析。结果乙状窦前入路由乳突开始磨除岩骨,避开乙状窦和颈静脉球,经过面神经垂直段、听骨链、迷路,到达膝状神经节时,显露面神经。乙状窦后入路由横窦下方开颅,经过小脑半球,到达内听道时磨除岩骨,经过面听神经复合体,到达膝状神经节,路径中包含听骨链和迷路。手术路径和迷路体积测量：乙状窦后入路＞乙状窦前入路;面听神经复合体和听骨链体积：乙状窦前入路＞乙状窦后入路,差异均有统计学意义（P ＜0．05）。乙状窦后入路中小脑半球体积为（462．72±20．87）mm3,乙状窦前入路不包含小脑半球。两种路径中骨性结构（不包含听骨链）体积的差异无统计学意义（P＞0．05）。结论在磨除岩骨显露膝状神经节的路径中,乙状窦前入路有助于减少迷路损伤范围,乙状窦后入路有助于减少听骨链损伤范围并显露面听神经复合体。     

A study of some of the ascending and descending vestibular pathways in the pigeon (Columba livia) using anterograde transneuronal autoradiography

A mixture of tritiated proline and fucose was injected into the endolymph of one of the membranous labyrinths of each of 5 white king pigeons (Columba livia). The membranous labyrinth was resealed and the animals were allowed to survive for 15 days. Brains and upper parts of the spinal cords were sectioned and processed by standard autoradiographic procedures. Clear labeling was noted in structures usually associated with both the ascending auditory pathways and the ascending and descending vestibular pathways. Vestibular structures ipsilateral to the injected labyrinth which contained heavy labeling were Scarpa's ganglion and all 6 vestibular nuclei. No labeling was noted in the contralateral Scarpa's ganglion and sparce, if any, labeling was noted in the contralateral vestibular nuclei. Contralateral structures associated with ascending vestibulo-ocular pathways which contained heavy labeling were the medial longitudinal fasciculus, abducens nucleus, trochlear nucleus, and two parts of the oculomotor nucleus--the dorsolateral part and the ventromedial part. Less heavily labeled ipsilateral vestibulo-ocular-related structures included the medial longitudinal fasciculus, abducens nucleus and the ventrolateral edge of the trochlear nucleus. The dorsomedial part of the oculomotor nucleus was heavily labeled on the side ipsilateral to the injected labyrinth. Slight, if any, labeling was noted in either the ipsilateral or contralateral brachium conjunctivum or regions corresponding to the mammalian ascending tract of Deiters. The medullary core of most folia but primarily the medullary core and granular areas of folia IX and X of the cerebellum were labeled.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immune response after neonatal transfer of a human factor IX-expressing retroviral vector in dogs, cats, and mice

INTRODUCTION: Gene therapy could prevent bleeding in hemophilia. However, antibodies could inhibit coagulation, while cytotoxic T lymphocytes could destroy modified cells. The immaturity of the newborn immune system might prevent these immune responses from occurring after neonatal gene therapy. MATERIALS AND METHODS: Newborn dogs, cats, or mice were injected intravenously with a retroviral vector expressing human Factor IX. Plasma was evaluated for antigen and anti-human Factor IX antibodies. Cytotoxic T lymphocyte responses were evaluated indirectly by analysis of retroviral vector RNA in liver. Lymphocytes were evaluated for cytokine secretion and the ability to suppress an immune response to human Factor IX in mice. RESULTS AND CONCLUSIONS: Hemophilia B dogs that achieved 942+/-500 ng/ml (19% normal) or 5+/-0.4 ng/ml (0.1% normal) of human Factor IX in plasma only bled 0 or 1.2 times per year, respectively, and were tolerant to infusion of human Factor IX. Normal cats expressed human Factor IX at 118+/-29 ng/ml (2% normal) in plasma without antibody formation. However, plasma human Factor IX disappeared at late times in 1 of 4 cats, which was probably due to a cytotoxic T lymphocyte response that destroyed cells with high expression. C3H mice were tolerant to human Factor IX after neonatal gene therapy, which may involve clonal deletion of human Factor IX-responsive cells. These data demonstrate that neonatal gene therapy does not induce antibodies to human Factor IX in dogs, cats, or mice. The putative cytotoxic T lymphocyte response in one cat requires further study.     

Properties of central vestibular neurons fired by stimulation of the saccular nerve

In 4 cats all vestibular afferents in one labyrinth except those innervating the saccular macula were transected and allowed to degenerate. 23–53 days after the initial surgery the central connections of the remaining saccular nerve were studied under chloralose anesthesia. Stimulation of the saccular nerve evoked N₁ field potentials in the ipsilateral lateral and descending vestibular nuclei; little or no field potential activity was seen in the superior nucleus. The distribution of field potentials overlapped with that of neurons of origin of the vestibulospinal tracts. Forty-two neurons in the ipsilateral vestibular nuclei, many in the lateral nucleus, responded, often monosynaptically, to stimulation of the saccular nerve with single or double shocks; some of the neurons projected to the spinal cord. All saccular-fired neurons were tested for commissural actions by stimulation of the contralateral vestibular nerve. Many were facilitated, almost none were inhibited. In agreement with earlier work, we conclude that commissural inhibition may be a property of the canal system only.     

Spiral and vestibular ganglion estimates in archival temporal bones obtained by design based stereology and Abercrombie methods

The objective of this study was to make direct comparisons of the estimates of spiral and vestibular neuronal number in human archival temporal bone specimens using design-based stereology with those using the assumption-based Abercrombie method. Archival human temporal bone specimens from subjects ranging in age from 16 to 80 years old were used. The number of spiral and vestibular ganglia neurons within the counting areas was estimated using the stereology-optical disector technique and compared with estimates obtained using the assumption-based Abercrombie method on the same specimens. Using the optical disector method, there was an average of 41,480 (coefficient of variation=0.12) spiral ganglia neurons and 28,930 (coefficient of variation=0.15) vestibular ganglia neurons. The mean coefficient of error was 0.076 for the spiral ganglion estimates, and 0.091 for the vestibular ganglion estimates. Using the Abercrombie correction method of two-dimensional analysis, an average of 23,110 (coefficient of variation of 0.08) spiral ganglia neurons, and 16,225 vestibular ganglia neurons (coefficient of variation of 0.15) was obtained. We found that there was a large disparity between the estimates with a significant 44% underestimation of the spiral and vestibular ganglion counts obtained using the Abercrombie method when compared with estimates using the optical disector method.     

The vestibular system and cerebellum in organic mercury intoxication; an otolaryngological and neuropathological investigation on 14 autopsy cases in Niigata

The vestibular system consisting of vestibular ganglion, nerve and inferior, medial, lateral and superior nuclei and fastigial nucleus, cerebellar vermis, flocculus and hemisphere in 14 autopsy cases of methyl mercury intoxication in Niigata and 12 age-matched controls were examined neuropathologically. The findings were evaluated semiquantitatively, that is, -; normal, +/-; gliosis alone, +; loss of neurons or myelinated fibers less than about 40%, ++; loss of neurons from about 41 to 80%, ; loss of neurons more than about 81%. The results were compared to the records of the equilibrium function of those patients. The examinations on the equilibrium function revealed positive findings in the optokinetic and positional nystagmus, eye tracking, Mann or Stepping test in many of the patients. There were no remarkable histological alterations in the vestibular ganglion and nerve of the patients. Moderate and diffuse gliosis with slight shrinkage of neurons were observed in the vestibular and fastigial nuclei of all the patients. Slight loss of neurons in various vestibular nuclei was examined in only 4 patients. The fastigial nucleus showed no evident loss of neurons. In contrast, the cerebellum showed diffuse loss of Purkinje and granule cells, the degree of which was higher in the vermis than in the hemisphere and the flocculus. In the controls, the vestibular nerve and nuclei showed no remarkable alteration even in eight decade subjects. However, the Purkinje cells in the vermis seemed to have a tendency to decrease in aging. The dysequilibrium in the patient of methyl mercury intoxication did not seem to be correspond to the degeneration of the vestibular ganglion, nerve or nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)     

Localization of substance P-like immunoreactivity in guinea pig vestibular endorgans and the vestibular ganglion.

The immunocytochemical distribution of substance P (SP) in guinea pig vestibular endorgans and the vestibular ganglion was investigated. Two kinds of SP-immunoreactive fibers were distinguished. Most were thick, and found around or beneath sensory hair cells. These SP-immunoreactive fibers were distributed predominantly on the slope of the crista and the peripheral region of the macula. By electron microscopy, we confirmed this type of SP-like immunoreactivity to be restricted within primary afferent neurons. Some vestibular ganglion cells also showed SP-like immunoreactivity, suggesting that SP is present in some primary afferent neurons, and is involved in afferent neurotransmission. The characteristic distribution of SP may indicate functional differences within each endorgan. The other group of immunoreactive nerve fibers, varicous thin fibers, could be found in the stroma of vestibular endorgans, nerve trunk, vestibular ganglion, and along blood vessels of the vestibular ganglion. These fibers may have a different origin, and have an influence on blood flow and certain other functions.     

Location of abducens afferent neurons in the cat.

The sites of afferent neurons to the abducens nucleus were determined by the use of horseradish peroxidase hydraulically placed into the VIth nucleus in nine cats. Labeled neurons were found bilaterally in the medial vestibular nuclei, the prepositus nucleus of the hypoglossus, the contralateral dorsomedial gigantocellular tegmental field, the contralateral reticular formation, and the ipsilateral vestibular nerve ganglion.     

Unbiased stereological quantification of neurons in the human vestibular ganglion

Vestibular ganglion (VG) neurons are bipolar neurons that relay peripheral vestibular information to the CNS. Neuron counts in normal humans provide a basis for quantitative studies on the effects of aging or pathological conditions in the audiovestibular systems. No prior study has employed unbiased stereological technique to count human VG neurons. This study used unbiased stereology in the form of the optical fractionator to estimate the total number of human VG neurons in archival temporal bone specimens. An average (+/- s.d.) of 27330+/-2593 neurons was found in specimens from five patients with no history of vestibular pathology. This result, a significant departure from results of past studies, provides the first unbiased baseline value to compare with future stereologically based studies on the human VG.     

Intravitreal macrophage activation enables cat retinal ganglion cells to regenerate injured axons into the mature optic nerve

In mature mammals, retinal ganglion cells (RGCs) are generally unable to regenerate injured axons into the optic nerve. Here, we report that an intravitreal injection of either of two macrophage activators, oxidized galectin-1 or zymosan, strongly enhanced the regeneration of transected RGC axons beyond an optic nerve crush site in adult cats. Using WGA-HRP as an anterograde tracer, we found that injection of either macrophage activator caused many axons to grow into the distal optic nerve when evaluated 14 days later, with the strongest effects seen after injecting 100 ng of galectin-1. Elongation continued for at least another 2 weeks. Control eyes injected with saline contained very few labeled axons extending across the crush site. Elevation of intracellular cAMP levels using forskolin also enhanced regeneration beyond the crush site to some extent, but this treatment did not augment the effect of galectin-1 any further. These results indicate that RGCs of adult cats are capable of reverting to an active growth state and at least partially overcoming an inhibitory CNS environment as a result of intravitreal macrophage activation.     

Quantitative analysis of the retinal ganglion cell layer and optic nerve of the barn owl Tyto alba

The visual capacity of the common barn owl (Tyto alba) was studied by quantitative analysis of the retina and optic nerve. Cell counts in the ganglion cell layer of the whole-mounted retina revealed a temporal area centralis with peak cell density of 12,500 cells/mm2 and a horizontal streak of high cell density extending from the area centralis into the nasal retina. Integration of the ganglion cell density map gave an estimated total of 1.4 million cells for the ganglion cell layer. Electron microscopy of a single, complete section of the optic nerve revealed a bimodal fiber diameter spectrum (modes at 0.3 and 0.9 microns; bin width = 0.2 microns), with diameters ranging from 0.15 microns (unmyelinated) to 6.05 microns (myelinated, sheath included). The total axon count for the optic nerve was estimated from sample counts to be about 680,000 axons (25% unmyelinated). Therefore, roughly half of the cells in the retinal ganglion cell layer do not send axons into the optic nerve. With certain assumptions, the data predict a visual spatial acuity for barn owls on the order of 8 cycles/degree, a value similar to the known behaviorally measured acuities of masked owls (10 cycles/degree) and domestic cats (6 cycles/degree).     

The Relationship of Microglial Cells to Dying Neurons During Natural Neuronal Cell Death and Axotomy-induced Degeneration of the Rat Retina

The interactions between dying neurons and phagocytotic cells within the developing and injured retina remain controversial. The present work explored the role of microglia and investigated whether so-called resident microglial cells are permanently responsible for removing cell debris whenever it is produced. As a first goal, I characterized some quantitative and morphometric features of the small ipsilateral retinocollicular projections and analysed the permanent function of phagocytosing microglia with these projections as a paradigm. To achieve this, I combined the fluorescent dyes Dil and 4Di-10ASP, both of which persist in the labelled ganglion cells after injection into the superior colliculus (SC), and retrograde labelling. After neuronal degradation, the dyes accompany the degradation products, become interiorized and then persist within the phagocytosing microglia. Consequently, early labelling of microglial cells can be assessed by injecting one dye into the SC during the first postnatal day of life, that is, prior to advanced natural neuronal cell death. Labelling of the remaining ipsilaterally projecting neurons with the second dye following intraorbital axotomy in adulthood and during subsequent neuronal death would therefore result in double labelling of some microglial cells, if these were involved in phagocytosis during both the natural and the induced phases of neuronal degradation. The ganglion cells which survived natural neuronal cell death remained fluorescent for 3 months after labelling with either dye on the day of the animal's birth, indicating that both fluorescent probes persisted within neurons. Quantitatively, 1770+/-220 ganglion cells/mm2 were labelled within the contralateral retina and a total population of 1442+/-120 cells/retina were observed within the periphery of the inferior/temporal quadrant of the ipsilateral retina. A smaller, ipsilateral projection of 150+/-24 cells/retina was uniformly scattered throughout the rest of the retinal surface. Transient projections of ganglion cells to either the contralateral or the ipsilateral colliculi and death of labelled ganglion cells during the first postnatal days resulted in labelling of 210+/-36 microglial cells/mm2 within the contralateral retina and a total number of 800+/-120 cells/retina within the inferior/temporal and 200+/-22 cells/retina within the rest of the retina. These labelled microglial cells were observed in adulthood and indicated that after taking away the neuronal cell debris they persisted within the retinal tissue. The small number of prelabelled ganglion cells which formed persistent ipsilateral projections until adulthood were axotomized by transecting the optic nerve, and resulted in additional labelling of microglial cells with the second fluorescent dye as well. Double-labelled microglia were observed within the inferior/temporal quadrant (3500+/-240 cells/retina) and to a lesser extent (340+/-40 cells/retina) scattered over the entire retinal surface. The chronotopological sequence of microglial labelling paralleled that of ganglion cell degeneration. Injection of protease inhibitors into the vitreous body during optic nerve transection retarded retrograde glial cell degeneration, probably by blocking microglial proteases. The results directly proved that the same microglial cells which remove neuronal cell debris in the postnatal retina were reactivated later in life to proteolytically degrade and then phagocytose neurons which had altered because of the axotomy.     

Influences of neck afferents on sympathetic and respiratory nerve activity

It is well established that the vestibular system influences the sympathetic nervous system and the respiratory system; presumably, vestibulosympathetic and vestibulorespiratory responses participate in maintaining stable blood pressure and blood oxygenation during movement and changes in posture. Many brainstem neurons that generate vestibulospinal reflexes integrate signals from the labyrinth and neck muscles to distinguish between head movements on a stable body and whole body movements. In the present study, responses were recorded from the splanchnic (sympathetic), hypoglossal (inspiratory) and abdominal (expiratory) nerves during stimulation of the C2 dorsal root ganglion or C2 or C3 nerve branches innervating dorsal neck muscles. Stimulation of neck afferents using low current intensities, in many cases less than twice the threshold for producing an afferent volley recordable from the cord dorsum, elicited changes in sympathetic and respiratory nerve activity. These data suggest that head rotation on a stable body would elicit both cervical and vestibular inputs to respiratory motoneurons and sympathetic preganglionic neurons. The effects of cervical afferent stimulation on abdominal, splanchnic and hypoglossal nerve activity were not abolished by transection of the brainstem caudal to the vestibular nuclei; thus, pathways in addition to those involving the vestibular nuclei are involved in relaying cervical inputs to sympathetic preganglionic neurons and respiratory motoneurons. Transection of the C1-3 dorsal roots enhanced responses of the splanchnic and abdominal nerves to pitch head rotations on a fixed body but diminished responses of the hypoglossal nerve. Thus, neck and vestibular afferent influences on activity of respiratory pump muscles and sympathetic outflow appear to be antagonistic, so that responses will occur during whole body movements but not head movements on a stationary trunk. In contrast, neck and vestibular influences on tongue musculature are complementary, presumably to produce tongue protrusion either during movements of the head alone or of the whole body.     

The contribution of the contralateral labyrinth to second order vestibular neuronal activity in the cat

Vestibular brain stem units of the horizontal canal in the awake C1 transected cat were examined in acute experiments before and after the contralateral vestibular nerve was cut. The latter procedure resulted in an immediate increase in mean resting rate from 19 to 45 spikes/sec and greater spontaneous fluctuations in firing rate. Mean sensitivity to constant accelerations from 2 to 16 degrees/sec2 was significantly reduced. In the 4-6 degrees/sec2 range, for example, mean sensitivity fell from 5.7 +/- 3.2 spike/sec/deg/sec2 (range 0.7-13.6, n = 107) to 2.8 +/- 1.4 (range 0.2-5.5, n = 29). Mean sensitivity to 4-6 degrees/sec2 deceleration was reduced from about 4.5 to 3.0. On the other hand, time constants and the ratio of adapting to non-adapting units was unchanged. Removal of the midline cerebellum, including the vermis and fastigial nuclei in a portion of the animals, did not materially alter the above results. It is concluded that the contralateral labyrinth, acting via the vestibular brain stem commissural pathway, not only exerts a powerful effect on the resting activity of brain stem canal vestibular neurons, but also on their response to acceleration.     

Effects of unilateral vestibular ganglionectomy on glutaminase activity in the vestibular nerve root and vestibular nuclear complex of the rat

The metabolism of glutamate, the most likely neurotransmitter of vestibular ganglion cells, includes synthesis from glutamine by the enzyme glutaminase. We used microdissection combined with a fluorometric assay to measure glutaminase activity in the vestibular nerve root and nuclei of rats with unilateral vestibular ganglionectomy. Glutaminase activity in the lesioned-side vestibular nerve root decreased by 62% at 4 days after ganglionectomy and remained at similar values through 30 days. No change occurred in the contralateral vestibular nerve root. Glutaminase activity changes in the vestibular nuclei were lesser in magnitude and more complex, including contralateral increases as well as ipsilateral decreases. At 4 days after ganglionectomy, glutaminase activity was 10-20% lower in individual lesioned-side nuclei compared with their contralateral counterparts. By 14 and 30 days after ganglionectomy, there were no statistically significant differences between the nuclei on the two sides. This transient asymmetry of glutaminase activities in the vestibular nuclei contrasts with the sustained asymmetry in the vestibular nerve root and suggests that intrinsic, commissural, or descending pathways are involved in the recovery of chemical symmetry. This recovery resembles our previous finding for glutamate concentrations in the vestibular nuclei and may partially underlie central vestibular compensation after peripheral lesions.     

Vestibular influence on tongue activity

The vestibular system was electrically stimulated in cats anesthetized with ketamine. Peripheral stimulation by an electrode positioned in the vestibule evoked torsional contralateral eye deviations and an electromyogram (EMG) response in a contralateral dorsal neck extensor. Consistently associated with this well documented vestibular pattern was an EMG response in tongue protrusive muscles, at a latency of 13 +/- 5 (means +/- SD) ms. Stimulation in a specific part of the rostroventral lateral vestibular nucleus elicited the same combination of responses: torsional contralateral eye deviations, dorsal neck EMG, and tongue EMG at a latency of 14 +/- 3 ms. Possible tongue activation by current spread to peripheral and central neural structures was examined in detail. Cerebellar, V, VII, cochlear, IX, X, and XII nerve influences were considered. On the basis of combined evidence, it was concluded that the vestibular system does influence tongue activity.     

Endothelin acts in feline and canine cerebral arteries from the adventitial side

We investigated the in vivo vasoconstrictor effect of endothelin, a recently characterized vasoconstrictor peptide from vascular endothelium, in the basilar arteries of five cats and five dogs. Basilar artery caliber was angiographically measured under anesthesia before (control) and after either vertebral artery infusion or cisternal injection of the peptide. In cats, 5-500 pmol endothelin induced a dose-dependent basilar artery contraction in vivo when injected intracisternally; within 3 minutes after injection of 500 pmol endothelin, basilar artery caliber was decreased by 73 +/- 4% compared with control diameter before injection. The vasoconstriction was extremely long-lasting; no significant recovery of basilar artery caliber was observed for up to 2 hours after injection. In contrast, infusion of up to 3,000 pmol endothelin into the vertebral artery had no appreciable effect on basilar artery caliber. Similar results were obtained in dogs; vasoconstriction was maintained for as long as 12 hours. Our observations suggest that endothelin acts in cerebral vessels from the adventitial side, not from the luminal side, possibly due to the presence of the blood-arterial wall barrier. The long-lasting nature of endothelin-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.     

Distribution of herpes simplex virus type 1 in human geniculate and vestibular ganglia: implications for vestibular neuritis.

Vestibular neuritis is a common cause of partial unilateral vestibular paralysis, which usually spares posterior semicircular canal function. The cause is assumed to be a viral reactivation of latent herpes simplex virus type 1 (HSV-1) in human vestibular ganglia. The existence of an anastomosis between the intermediate nerve and the superior vestibular nerve suggests the question of whether selective affliction of the superior vestibular nerve is the result of migration of HSV-1 from the geniculate ganglion along this faciovestibular anastomosis. We determined the distribution of HSV-1 among geniculate ganglia, vestibular ganglia, and within Scarpa's ganglion by examining 35 human temporal bones by polymerase chain reaction. HSV-1 was found in 66% of geniculate ganglia and 60% of vestibular ganglia; all examined parts of vestibular ganglia were almost equally HSV-1 infected. Our data provided no support for viral migration along this anastomosis or for a preferential latency of HSV-1 in the superior vestibular nerve. We suggest that the common double innervation of the posterior ampulla by two nerves running in two separate bony canals could offer an alternative explanation for the regular sparing of posterior canal function in vestibular neuritis.     

Comparison between pial and intraparenchymal vascular responses to cervical sympathetic stimulation in cats. Part 1. Under normal resting conditions

To investigate the role of sympathetic regulation in both resistance and capacitance vessels in cerebral circulation, the response of pial and intraparenchymal vessels to sympathetic nerve stimulation were simultaneously examined in 14 cats by means of a newly developed video camera photoelectric system. The system consisted of a video camera system for measurement of pial vascular diameters and a photoelectric apparatus for estimating regional cerebral blood volume in the intraparenchymal vessels. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min. Initially, both the pial and intraparenchymal vessels constricted. The large pial arteries (173 +/- 25 micron, mean +/- SEM) remained constricted throughout the stimulation, whereas the intraparenchymal vessels began to dilate after the initial constriction and exceeded the control level at 175 +/- 25 s despite continued stimulation. In conclusion, such sympathetic nerve stimulation is considered to exert a constrictive effect on the intraparenchymal as well as the pial vessels at the early stage. The compensatory dilation of the intraparenchymal vessels was delayed 3 min after initiation of the stimulation.