Experimental chronic lead poisoning.

In the peripheral nerve, the distal part of the nerve fibers was remarkably damaged--periaxial segmental demyelination--while the proximal part of nerve fibers was only slightly affected. In the CNS, perivascular edema of the small blood vessels and capillaries was observed in the cerebral cortex and cerebellar cortex. All endothelial cells of these blood vessels showed a high electron density with many pinocytotic vesicles and ribosomes. Following these changes, the nerve fibers adjacent to the edema were destroyed. The above-mentioned findings seem to indicate that lead induces a toxic effect on the blood vessel and produces perivascular edema in the CNS of adult animals. This may induce brain dysfunction.     

5'-nucleotidase localization in the brains and spinal cords of adult normal and dysmyelinating mutant (shiverer) mice

Immunocytochemical staining with the antibody against mouse liver 5'-nucleotidase revealed 5'-nucleotidase antigenicity in myelinated fibers in the brains and in myelinated fibers and some interfascicular oligodendroglia in the spinal cords of normal adult mice. Although the 5'-nucleotidase specific activity in adult shiverer mouse CNS tissue homogenates had been shown to be normal, immunocytochemical staining with anti-mouse-5'-nucleotidase could be demonstrated in CNS tissue sections from only 2 out of 10 of the mutant animals. In tissue from these animals the staining, which was relatively faint, was localized specifically to cell-bodies, usually arranged in rows, and to material oriented parallel to nerve fibers. This pattern of immunostaining with anti-5'-nucleotidase resembled the immunostaining with anti-carbonic anhydrase but not with anti-glial-fibrillary-acidic-protein. This suggested that the rows of cells were oligodendrocytes, not astrocytes, and that the material parallel to nerve fibers might consist of oligodendrocyte processes wrapped loosely around axons. The antibody against rat 5'-nucleotidase, as distinguished from mouse, immunostained only the blood vessels in the shiverer mouse CNS, a finding similar to a previous observation in the normal mouse CNS. From these findings it was inferred that the primary loci of 5'-nucleotidase in the shiverer mouse CNS were interfascicular oligodendrocytes, their processes, and blood vessels, and in the normal mouse CNS, the myelin in some tracts, the blood vessels, and some interfascicular oligodendrocytes.     

Quantitative image analysis of the density and pattern of adrenergic innervation of blood vessels of rat spinal cord

The density and pattern of the noradrenergic innervation of the main extramedullary blood vessels of the rat spinal cord was studied using combined glyoxylic acid histofluorescence and quantitative image analysis techniques. The anterior spinal artery has a perivascular plexus of fine noradrenergic nerves rich in varicosities; the central artery has nerve fibers of various sizes; and the posterior spinal vein has a limited plexus of noradrenergic nerve fibers. The possible significance of the noradrenergic innervation of extramedullary spinal cord blood vessels is discussed.     

Subcellular localization of nitric oxide synthase in the cerebral ventricular system,subfornical organ,area postrema,and blood vessels of the rat brain

The distribution of neuronal nitric oxide synthase (nNOS) has been studied in the more rostral portion of the lateral ventricle, subfornical organ, area postrema and blood vessels of the rat central nervous system. nNOS was located by means of a specific polyclonal antibody, by using light and electron microscopy. Light microscopy showed immunoreactive varicose nerve fibers and terminal boutons-like structures in the lateral ventricle, positioned in supra- and subependimal areas. The spatial relationships between immunoreactive neuronal processes and the wall of the intracerebral blood vessels were studied. Electron microscopy showed numerous nerve fibers in the wall of the lateral ventricle; many were nNos-immunoreactive and established very close contact with ependymal cells. Immunoreactive neurons and processes were found in the subependymal plate of the ventricular wall, the subfornical organ, the area postrema, and the circularis nucleus of the hypothalamus. In these last three areas, the immunoreactive neurons were found close to the perivascular space of fenestrated and nonfenestrated blood vessels. The nNOS immunoreactivity was localized to the endoplasmic reticulum, cisterns, ribosomes, neurotubules, and in the inner part of the external membrane. In the terminal boutons, the reaction product was found surrounding the vesicle membranes. This distribution showed nNOS as a predominantly membrane-bound protein. The nitrergic nerve fibers present in the wall of the ventricular system might regulate metabolic functions as well as neurotransmission in the subfornical organ, area postrema and circularis nucleus of the hypothalamus. J Comp Neurol 378:522–534, 1997. © 1997 Wiley-Liss, Inc.     

Development of the blood vessels and extracellular spaces during postnatal maturation of rat cerebral cortex

As part of a larger study of the development of postnatal rat cerebral cortex, this report deals with the maturation of the cortex as a tissue from birth to twenty-one days of age. The changes in the numerical density of cells and blood vessels and the thickness of the cortex at successive ages were followed on light micrographs, and both were related to the ultrastructural observations on routine electron microscopic preparations. The maturation of the cortex is divided into two periods: The first ten days during which the growth to adult dimensions occurs and few patent blood vessels but large extracellular spaces are to be found, and the second ten days in which the majority of the vessels develop patent lumina, the perivascular sheath of astrocyte end-feet develops, and the large extracellular spaces disappear concomitant with the maturation of the neuropil. The blood vessels appear to develop during the first ten days as solid cords of mesodermal elements which form a network of primordial vessels with thick walls and slit-like lumina containing a flocculent material. The formation of a blood filled, patent lumen apparently occurs synchronously over a brief period of time for the majority of the vessels during the early part of the second ten-day period. The basal lamina is ill-defined initially but takes on mature appearance parallel with the development of the perivascular glial sheath. The volume of the extracellular space was found to be largest during the phase of rapid growth of axons and dendrites when few patent vessels exist. The disappearance of these large extracellular spaces during maturation of the blood vessels and neuropil is discussed in terms of the possible artifactitious nature of these spaces in both immature and mature cortex.     

Distribution of adrenergic innervation of blood vessels in peripheral nerve

The distribution of adrenergic innervation of microvessels in the extrafascicular and endoneurial compartments of rat tibial nerve was examined with glyoxylic acid-induced and formaldehyde-induced histofluorescence methods. Periarterial and arteriolar adrenergic nerves were present in the epineurium-perineurium suggesting that blood flow in the extrafascicular connective tissue is under neurogenic influence. In contrast, blood vessels in the nerve endoneurium were not associated with histofluorescent nerve fibers. The absence of perivascular adrenergic innervation in the endoneurium suggests that regulation of vascular function within the endoneurium is not under neurogenic control.     

Neuropeptide Y-immunoreactive primary afferents in the dental pulp and periodontal ligament following nerve injury to the inferior alveolar nerve in the rat

The distribution of neuropeptide Y (NPY)-immunoreactive (IR) primary afferents in the dental pulp and periodontal ligament of the rat mandible were examined following combined chronic constriction injury (CCI) of the inferior alveolar nerve (IAN) and sympathectomy of the superior cervical ganglion (SCG). NPY-IR nerve fibers were observed around the blood vessels in the trigeminal ganglion, dental pulp and periodontal ligament in normal animals. Following combined CCI of the IAN and sympathectomy of SCG (SCGx), perivascular NPY-IR nerve fibers originating from SCG disappeared completely, but many NPY-IR nerve fibers coming from the trigeminal ganglion appeared in the dental pulp and periodontal ligament. In the molar dental pulp, thick NPY-IR nerve fibers were observed within the nerve bundle, and some thin NPY-IR nerve fibers ran towards the odontoblast layer; very few NPY-IR nerve fibers were observed in the incisor pulp. In the periodontal ligament of molar, thick NPY-IR nerve fibers appeared at the alveolar part following combined CCI of IAN and SCGx. In the lingual portion of the periodontal ligament of the incisor, many thick NPY-IR nerve fibers were observed. These occasionally showed a tree-like appearance, resembling immature Ruffini endings; slowly adapting mechanoreceptors. The present results indicate that periodontal mechanoreceptors are among the main targets of injury-evoked NPY following IAN injury.     

Peripheral nerve pathological findings in familial amyloid polyneuropathy: a correlative study of proximal sciatic nerve and sural nerve lesions

To analyze the peripheral nerve pathological abnormalities in familial amyloid polyneuropathy, a correlative pathological study was carried out on the spinal nerve roots, proximal sciatic nerves, sural nerves, and brachial plexuses from 3 patients with the disease in Japan. The spinal nerve roots appeared to be unaffected except for amyloid deposition on the epineurium. In sciatic nerves and brachial plexuses the nerve lesions had a multifocal distribution, showing prominent interstitial edema in the endoneurium frequently adjacent to deposits of amyloid; in these regions the nerve fibers were severely depleted. A teased-fiber study revealed that segmental demyelination was the predominant type of nerve fiber abnormality. However, these findings were not seen in the sural nerves; instead a diffuse fiber loss with axonal degeneration was observed. It is suggested that multifocal lesions in the proximal portions of the long extremity nerves could summate distally to produce a symmetrical polyneuropathy in the disease. In addition to a space-occupying effect of amyloid deposits in the endoneurium, severe endoneurial edema associated with amyloid deposition in blood vessels and the endoneurial interstitium may induce ischemia in nerve fibers, thus causing the progressive polyneuropathy in this disorder.     

SIV-induced impairment of neurovascular repair: a potential role for VEGF

Peripheral nerves and blood vessels travel together closely during development but little is known about their interactions post-injury. The SIV-infected pigtailed macaque model of human immunodeficiency virus (HIV) recapitulates peripheral nervous system pathology of HIV infection. In this study, we assessed the effect of SIV infection on neurovascular regrowth using a validated excisional axotomy model. Six uninfected and five SIV-infected macaques were studied 14 and 70 days after axotomy to characterize regenerating vessels and axons. Blood vessel extension preceded the appearance of regenerating nerve fibers suggesting that vessels serve as scaffolding to guide regenerating axons through extracellular matrix. Vascular endothelial growth factor (VEGF) was expressed along vascular silhouettes by endothelial cells, pericytes, and perivascular cells. VEGF expression correlated with dermal nerve (r=0.68, p=0.01) and epidermal nerve fiber regrowth (r=0.63, p=0.02). No difference in blood vessel growth was observed between SIV-infected and control macaques. In contrast, SIV-infected animals demonstrated altered length, pruning and arborization of nerve fibers as well as alteration of VEGF expression. These results reinforce earlier human primate findings that vessel growth precedes and influences axonal regeneration. The consistency of these observations across human and non-human primates validates the use of the pigtailed-macaque as a preclinical model.     

Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages

Production of prostaglandins is a critical step in transducing immune stimuli into central nervous system (CNS) responses, but the cellular source of prostaglandins responsible for CNS signalling is unknown. Cyclooxygenase catalyzes the rate-limiting step in the synthesis of prostaglandins and exists in two isoforms. Regulation of the inducible isoform, cyclooxygenase 2, is thought to play a key role in the brain's response to acute inflammatory stimuli. In this paper, we report that intravenous lipopolysaccharide (LPS or endotoxin) induces cyclooxygenase 2-like immunoreactivity in cells closely associated with brain blood vessels and in cells in the meninges. Neuronal staining was not noticeably altered or induced in any brain region by endotoxin challenge. Furthermore, many of the cells also were stained with a perivascular microglial/macrophage-specific antibody, indicating that intravenous LPS induces cyclooxygenase in perivascular microglia along blood vessels and in meningeal macrophages at the edge of the brain. These findings suggest that perivascular microglia and meningeal macrophages throughout the brain may be the cellular source of prostaglandins following systemic immune challenge. We hypothesize that distinct components of the CNS response to immune system activation may be mediated by prostaglandins produced at specific intracranial sites such as the preoptic area (altered sleep and thermoregulation), medulla (adrenal corticosteroid response), and cerebral cortex (headache and encephalopathy). J. Comp. Neurol. 381:119-129, 1997. © 1997 Wiley-Liss, Inc.     

A cholinergic innervation of the bovine pineal gland visualized by immunohistochemical detection of choline acetyltransferase-immunoreactive nerve fibers

An immunohistochemical investigation of the bovine pineal gland was performed using both a rabbit polyclonal antibody and a rat monoclonal antibody against choline acetyltransferase (ChAT). A network of ChAT-immunoreactive (IR) nerve fibers was located throughout the pineal gland, both in the perivascular spaces and between the pinealocytes. Most of the intrapineal ChAT-IR nerve fibers were endowed with varicosities. In addition, some ChAT-IR intrapineal neurons were found, often located at the base of the gland near the pineal recess. Within the habenular nucleus and pineal stalk, ChAT-IR perikarya and nerve fibers were also present. Some of these fibers projected towards the pineal gland. A number of ChAT-IR nerves were also located in the posterior commissure and could be followed into the gland. At the caudal tip of the pineal gland, a bundle of ChAT-IR nerve fibers was observed to penetrate into the gland together with blood vessels. The presence of a cholinergic innervation of the bovine pineal gland, together with previous demonstration of the presence of choline acetyltransferase and muscarinic receptor binding sites in the bovine pineal gland, indicates a functional influence of a cholinergic nervous system on the pinealocyte.     

Coexistence of nitric oxide synthase and neuropeptides in the mouse vomeronasal organ demonstrated by a combination of double immunofluorescence labeling and a multiple dye filter

Nitric oxide synthase (NOS)-immunofluorescence techniques were applied to the mouse vomeronasal organ. Immunoreactivity for NOS was found in the nerve fibers distributed in the receptor-free epithelium, and around the blood vessels and glands in the cavernous tissue. No NOS fibers were seen in the receptor area. A combination of double immunofluorescence labeling and multiple dye filter revealed that a part of the substance P (SP)-immunoreactive nerve fibers in the cavernous tissue contained NOS and that all the vasoactive intestinal polypeptide (VIP)-immunoreactive nerve fibers around the blood vessels and glands in the cavernous tissue contained NOS. A few SP-immunoreactive cell bodies in the trigeminal ganglion showed coexistence with NOS, and almost all VIP-immunoreactive cell bodies in the sphenopalatine ganglion showed coexistence with NOS. Immunoreactivity for NOS without VIP in the cell bodies in the sphenopalatine ganglion was also found. These results suggest that NOS-immunoreactive nerve fibers in the mouse vomeronasal organ originate from the trigeminal and the sphenopalatine ganglia, and may modulate the vascular tone and the glandular secretion. In addition, these functions may be controled in part by the interaction of nitric oxide and neuropeptides.     

A light and electron microscopic immunohistochemical study of vasoactive intestinal polypeptide- and substance P-containing nerve fibers along the cerebral blood vessels: comparison with aminergic and cholinergic nerve fibers

Vasoactive intestinal polypeptide (VIP)- and substance P-containing nerve fibers were observed in the cerebral blood vessels using an immunohistochemical technique. VIP-containing nerve fibers distributed in a spiral pattern, similar to that of muscle cells. Under electron microscopic observation, VIP-immunoreactive terminals lay close to a muscle cell in the inner layer of the adventitia. In contrast, substance P-containing nerve fibers showed a meshwork pattern in the outer layer of the adventitia. Using both acetylcholinesterase (AChE) staining and VIP immunohistochemistry, AChE-positive and VIP-immunoreactive nerve fibers revealed almost the same distribution in the same specimen. The present data suggest that VIP-containing nerve fibers may play a role in the smooth muscle control of the blood vessels, whereas substance P-containing nerve fibers may not take part in muscle control.     

Peptidergic innervation of the cerebral blood vessels--an immunohistochemical study

By an immunohistochemical technique, vasoactive polypeptide (VIP)-and substance P-containing nerve fibers are observed in the cerebral blood vessels. VIP-containing nerve fibers distribute in a spiral pattern, similar to the muscle cell distribution pattern. Under an electron microscopic observation, VIP-immunoreactive terminals lie just near to a muscle cell in the inner layer of the adventitia. In contrast, substance P-containing nerve fibers show a meshwork pattern in the outer layer of the adventitia. In combination of acetylcholinesterase (AChE) staining and VIP immunohistochemistry, AChE-positive and VIP-immunoreactive nerve fibers reveal almost same distribution in the same specimen. The present data suggest that VIP-containing nerve fibers may play a role of smooth muscle control of the blood vessels, while substance P-containing nerve fibers may not take part in muscle control.     

Associations between neuropeptide Y nerve terminals and intraparenchymal microvessels in rat and human cerebral cortex

Neuropeptide Y (NPY) can influence local brain perfusion, possibly via direct relationships with the microvascular bed. To evaluate this possibility, the authors quantitatively analyzed by light and electron microscopy the morphological associations between immunostained NPY neuronal elements and intraparenchymal microvessels in the rat and human cerebral cortex. At the light microscopic level in the rat frontoparietal cortex, about 16% of NPY neurons and large proximal processes as well as a subset of nerve terminals not affected by double sympathectomy were associated with penetrating arterioles and local microvessels. In human temporal cortex, a dense network of NPY nerve fibers was observed, many of which approached and/or contacted intracortical vessels. At the ultrastructural level, 14% of NPY axonal varicosities in the rat cerebral cortex were considered perivascular and associated with capillaries (∼70%) or microarterioles (∼30%). They were particularly enriched in the immediate vicinity (<0.25 μm) of the microvessels, where the perivascular astrocytic leaflets represented a frequent target. In human cerebral cortex, NPY varicosities were observed in proximity to microvessels corresponding primarily to capillaries. Perivascular NPY varicosities never established synaptic junctions with vascular or astroglial elements. The results show that central NPY nerve terminals associate with microvessels and perivascular astroglial cells in the rat and human cerebral cortex. Thus, NPY released from these nerves could possibly influence (via a parasynaptic mode of action) vascular and/or astrocytic functions depending on the distribution of NPY receptors in these cellular compartments. These results provide morphological support for the effects of NPY on brain perfusion and homeostasis. J. Comp. Neurol. 388:444–453, 1997. © 1997 Wiley-Liss, Inc.     

Effects of spinal cord transection and MK-801 on CGRP immunostaining in the rat urinary bladder.

Numerous studies have demonstrated that lesions in the CNS can alter the density of sensory nerve processes in peripheral organs. In the present study, rat spinal cords were transected at the second lumbar segmental level and the density of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the urinary bladder was examined. Additional rats had spinal cord transections followed by 12 days of treatment with the N-methyl-D-aspartate receptor antagonist, MK-801. In the bladders of control rats, CGRP-immunoreactive fibers were present as thick nerve trunks, perivascular plexi, and a fine meshwork of varicose nerve fibers. Twelve days following a spinal cord transection, the density of CGRP-immunoreactive nerve fibers was markedly reduced; occasional fibers appeared primarily as nonvaricose fine fibers. In bladders from rats receiving a spinal cord transection and MK-801 treatment, CGRP-immunoreactive fibers were abundantly distributed throughout the detrusor muscle; these fibers exhibited numerous varicosities as well as some enlarged terminal varicosities. These data demonstrate that (i) an upper motor neuron-type lesion markedly decreases the density of CGRP-immunoreactive peripheral afferent nerve processes and (ii) following a spinal cord transection, MK-801 appears to enhance the density of CGRP immunostaining in the bladder.     

Novel sites of aldose reductase immunolocalization in normal and streptozotocin-diabetic rats

Glucose metabolism by aldose reductase (AR) is implicated in the pathogenesis of many diabetic complications, including neuropathy. We have re-evaluated the distribution of AR in the sciatic nerve and dorsal root ganglion (DRG) of normal rats, expanded these observations to describe the location of AR in the spinal cord and footpad skin, and investigated whether diabetes alters the distribution of AR. In sciatic nerve, AR was restricted to cytoplasm of myelinated Schwann cells and endothelial cells of epineurial, but not endoneurial, blood vessels. AR immunoreactivity (IR) was present in satellite cells in the DRG. In skin, AR-IR was detected in vascular endothelial cells, Schwann cells of myelinated fibers, and axons of perivascular sympathetic nerves. AR was localized selectively to oligodendrocytes of the white matter of spinal cord. The distribution of AR-IR in sciatic nerve, DRG, skin, and spinal cord was not altered by up to 12 weeks of streptozotocin-induced diabetes. Identification of perineuronal satellite cells, oligodendrocytes, and perivascular sympathetic nerves as AR-expressing cells reveals them as cellular sites with the potential to contribute to diabetic neuropathy.     

Neuropeptide FF in the Rat Adrenal Gland: Presence, Distribution and Pharmacological Effects

Neuropeptide FF (NPFF, FLFQPQRFamide) is an FMRFamide-like octapeptide exhibiting antiopiate activity. The presence of both NPFF-immunoreactivity (NPFF-IR) and NPFF-specific receptors has been described in the mammalian central nervous system (CNS). The peripheral effects of NPFF indicate that NPFF-IR material is present outside the CNS. Biochemical and immunohistochemical methods enabled us to determine the presence and distribution of NPFF-IR in the rat adrenal gland. The amount of NPFF-IR material in whole gland was estimated by radioimmunoassay to be 19.00±4.00  fmol/gland. High performance liquid chromatography analysis of adrenal extracts revealed a single molecular form which coeluted with authentic NPFF. Demedullation decreased adrenal NPFF-IR content, indicating that NPFF-IR was present in both cortex and medulla. Light microscopy revealed NPFF-IR in beaded fibers confined in the outer part of the cortex and in medullary cells. Double-labeling with antityrosine-hydroxylase and anti-NPFF antibodies showed NPFF-IR in cortical catecholaminergic postganglionic fibers restricted to the subcapsular and glomerulosa zonae. NPFF-IR was also located in medullary chromaffin cells and in rays and islets of chromaffin cells dispersed throughout the cortex. Insulin-induced hypoglycemia did not alter NPFF-IR content. Denervation lowered adrenal NPFF-IR content. These data indicate that this peptide is present in nerve fibers of extrinsic origin. In vitro approaches using adrenal slices have shown that NPFF inhibited aldosterone release in a dose-dependent manner. Taken together, these data suggest that NPFF may participate in the control of aldosterone production and adrenal blood supply.     

Spread of malignant lymphoid cells into rat central nervous system with intact and disrupted blood–brain barrier

The pathways of spread of malignant lymphoid cells into the central nervous system (CNS) were studied using a T lymphoblastic leukaemia/lymphoma model of inbred PVG rats. The effects of intraperitoneal, intracarotid, intravenous, intrathecal and intracerebral routes of transplantation were analysed, and the significance of the blood–brain barrier (BBB) in preventing neoplastic cell invasion was studied by disrupting the BBB with focal cold injury. Extraneurally transplanted cells appeared first in the dura and subarachnoid space. From the latter they spread further into the perivascular space of penetrating cortical vessels. Parenchymal tumour cell foci were only seen in terminally ill rats, usually associated with damage to the vessel wall. Intrathecal transplantation did not accelerate the progression of the disease. Intracerebrally transplanted cells readily produced parenchymal infiltrates with diffuse invasion into the white matter, perivascular spreading into the cortex, and contralateral extension along the corpus callosum. Parenchymal invasion did not occur immediately after disruption of the BBB, but in the chronic phase neoplastic cells infiltrated the injured area. In conclusion, the model closely resembles human CNS leukaemia. Malignant cells appeared to enter the CNS through the deficient BBB of the subarachnoid vessels, whereas the BBB of the intracerebral vessels and perivascular glia limitans were very resistant to leukaemic cell invasion. This underlines the difference between the subarachnoid and perivascular v. intraparenchymal compartments. Preceding BBB damage may predispose to brain metastases. The parenchymal dissemination of malignant cells was similar to that in primary CNS lymphoma and it followed the same spreading pathways as the extracellular fluid.     

Uptake and release of serotonin in rat cerebrovascular nerves after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Serotonin released from platelets has been suggested as one substance causing the vasospasm following subarachnoid hemorrhage. We studied whether such serotonin is able to constrict pial vessels. METHODS: We studied the uptake of serotonin in pial perivascular nerves by immunohistochemistry. We measured the contractile response in rat basilar artery after in vitro incubation with serotonin and during electrical field stimulation of perivascular nerves following experimental subarachnoid hemorrhage. RESULTS: After incubation with serotonin, electrical field stimulation caused a tetrodotoxin- and ketanserin-blockable contractile response. We observed no such response in vessels from rats treated with 6-hydroxydopamine or after blockade of serotonin uptake. After subarachnoid hemorrhage, a pronounced network of serotonin-immunoreactive nerve fibers was demonstrated in the vessel wall. In vessels from control rats, no serotonin fibers were seen, and in vessels from 6-hydroxydopamine-treated animals with subarachnoid hemorrhage only a few such fibers were seen. Electrical field stimulation of the basilar artery from rats tested 2 or 16 hours (but not 10 minutes or 24 hours) after subarachnoid hemorrhage showed contractile responses that were prevented by tetrodotoxin, ketanserin, and prior 6-hydroxydopamine treatment. CONCLUSIONS: Our study demonstrates a capacity of the perivascular sympathetic nerves to take up serotonin both in vitro and during the early phase of subarachnoid hemorrhage. Such uptake may help to remove excess serotonin from the subarachnoid space. Only if serotonin is subsequently released upon nerve activation may minor smooth muscle contraction develop.