neuropeptide-y and Ischemic-Attack--Transient

The present paper reviews recent studies in monkey and man adding further to understanding of the role of perivascular peptides in the pathophysiology of subarachnoid haemorrhage. 1. The perivascular fibers, sympathetic fibers (storing noradrenaline, neuropeptide Y), parasympathetic fibers (storing acetylcholine, vasoactive intestinal peptide, peptide histidine methionine and neuropeptide Y) and sensory fibers (storing tachykinins, calcitonin gene-related peptide) were traced using True Blue in monkey. 2. Tracing studies of the monkey middle-cerebral artery (MCA) innervation confirmed earlier studies in rats and cats, with superior cervical and trigeminal ganglia as main immunostaining areas, and contralateral involvement in the superior cervical and trigeminal ganglia. Sphenopalatine immunostaining was scarce. 3. The release of neuropeptides in the external jugular vein in humans in the postoperative course after subarachnoid hemorrhage, using radioimmunoassay, was correlated to hemodynamical changes (vasoconstriction) monitored with Doppler ultrasound on middle cerebral (MCA) and internal carotid arteries (ICA)). 4. Neuropeptide Y-like immunoreactivity (NPY-LI) levels were increased compared to controls in patients with hemodynamic changes, and in some patients a relationship was found between velocities and NPY-LI. 5. Calcitonin gene-related peptide-LI levels were also increased in connection with vasospasm. In patients with MCA lesions a correlation of 0.61, p = 0.0002 was found between hemodynamic index (V MCA/V ICA) and CGRP-LI. The possible sympathetic and trigemino-cerebrovascular activation are discussed.

Topics: Animals; Benzofurans; Calcitonin Gene-Related Peptide; Cerebral Arteries; Cerebrovascular Circulation; Haplorhini; Hemodynamics; Humans; Ischemic Attack, Transient; Nerve Fibers; Neuropeptide Y; Neuropeptides; Subarachnoid Hemorrhage; Ultrasonography; Vasoconstriction

Modifications in the tissue concentration of vasoactive peptides (Endothelin, Calcitonin Gene Related Peptide, Atrial Natriuretic Peptide) and excitatory amino acids (glutamate, aspartate) were found in the nervous tissue of Mongolian gerbils after transient cerebral ischemia which was induced by unilateral occlusion of the common carotid artery for 30 min 4 h. In fact, immunostaining for these peptides was more intense in the ischemic tissue: the greatest increases of tissue immunoreactivity were observed for Endothelin; smaller differences were found for Calcitonin Gene Related Peptide and Atrial Natriuretic Peptide. Immunostaining for Neuropeptide Y, another vasoactive neuropeptide, was virtually unchanged. Infarct areas, when present, contained numerous Endothelin-immunoreactive cell bodies. On the contrary, the same areas were completely void of glutamate- or aspartate-immunostained neurons, normally present in the correspondent regions of the control tissue. The present results suggest that severe cerebral ischemia is paralleled by an unbalance of local vasoactive factors. The predominance of vasoconstrictor action of Endothelin might play a major role in the irreversible damage, together with the excitotoxic effect of the extracellular accumulation of excitatory amino acids, probably due to a leakage from neuronal cell somata, as suggested by the disappearance of glutamate- or aspartate-immunostained neurons.

Topics: Animals; Atrial Natriuretic Factor; Brain Damage, Chronic; Calcitonin Gene-Related Peptide; Carotid Stenosis; Endothelins; Excitatory Amino Acids; Gerbillinae; Ischemic Attack, Transient; Neurons; Neuropeptide Y; Vasoconstriction

Transient cerebral ischemia causes extensive cell death in hippocampal CA1 pyramidal cells and selective loss of interneurons in the dentate hilus. Many hippocampal interneurons can be classified by their contents of somatostatin (SS) and/or neuropeptide Y (NPY). Following ischemia in the rat, most of the NPY immunoreactivity is permanently lost in hippocampus. Furthermore, SS interneurons in the dentate hilus die, whereas CA1 interneurons survive and their expression of SS mRNA and peptide returns to preischemic levels within 16 days after ischemia. We have addressed the following questions: (1) Does the loss of NPY involve a specific downregulation in surviving CA1 interneurons that pre-ischemically expressed both SS and NPY? (2) Can the subpopulation of dying interneurons in hilus be identified from their preischemic coexpression of SS and NPY? We investigated the coexpression of SS mRNA and NPY peptide using combined in situ hybridization and immunocytochemistry. Cells containing one or both markers were counted in control sections and sections taken 2-16 days after ischemia from the hippocampal formation. In CA1, a decrease in the number of neurons containing NPY alone as well as a decrease in the number of neurons coexpressing NPY and SS was observed, whereas the number of neurons containing SS alone increased 16 days after ischemia. We conclude that neurons coexpressing SS and NPY before ischemia added to the number of neurons containing SS alone after ischemia, because NPY expression was selectively down regulated in the coexpressing population. In hilus, we demonstrated both survival and ischemic cell death of neurons expressing either SS, NPY or both, indicating that hilar interneurons dying from ischemia cannot unequivocally be identified from their preischemic colocalization of SS and NPY.

Topics: Animals; Cell Count; Hippocampus; Immunohistochemistry; In Situ Hybridization; Interneurons; Ischemic Attack, Transient; Male; Neuropeptide Y; Rats; Rats, Wistar; Somatostatin

Previously, using a middle cerebral artery occlusion model in Wistar rat, we showed autonomic disturbances similar to those seen clinically and observed striking neurochemical changes in cortical and subcortical sites at 5 days following stroke. The neurochemical changes may account for functional recovery and/or autonomic disturbances after focal ischemia. To understand the possible mechanisms and to facilitate future studies, it is necessary to define the time-courses of these changes. Using immunohistochemical staining with the peroxidase-antiperoxidase reaction, the changes in several neuropeptides over the peri-ischemic region and the ipsilateral central and basolateral nucleus of the amygdala were investigated at different times after middle cerebral artery occlusion. In the experimental group, neuropeptide Y immunoreactivity appeared to increase by 6 hours in the peri-ischemic region. Using image analysis to quantify the staining intensity, the change became statistically significant at 1 day, peaked around 3 days, and subsided at 10 days. There was a delayed increase in neuropeptide Y in the ipsilateral basolateral nucleus of the amygdala with a peak around 3 days. Immunoreactive staining for leucine-enkephalin, dynorphin, and neurotensin demonstrated an increase that was localized to the ipsilateral central nucleus of the amygdala with a peak around 3 days and a return to baseline levels by 10 days. The results support a specific time-course for each of the neuropeptides studied and indicate that a survival time of 3 days after focal ischemia is the critical period for examining the relationship between neuropeptide responses and neuronal or functional recovery.

Topics: Amygdala; Animals; Cerebral Cortex; Dynorphins; Enkephalin, Leucine; Ischemic Attack, Transient; Male; Neuropeptide Y; Neuropeptides; Neurotensin; Rats; Rats, Wistar; Time Factors; Tyrosine 3-Monooxygenase

The effect of acute cerebral occlusion on the distribution of cerebral perivascular nerves containing catecholamine, neuropeptide Y, and vasoactive intestinal peptide was studied in the three commonly used rat models of cerebral ischemia: Unilateral permanent middle cerebral artery (MCA) occlusion induced with an intraluminal thread technique; unilateral MCA occlusion produced by extraluminal electrocoagulation of the MCA; and transient arterial occlusion of the whole brain induced extracranially by the four-vessel clasp occlusion method for 30 minutes. Animals were sacrificed 3 days after occlusion and the distribution of the perivascular nerves of the MCA studied. Intraluminally occluded MCAs showed a similar distribution of perivascular nerves to those of contralateral and sham-operated MCAs. Extraluminally occluded MCAs demonstrated a marked decrease in perivascular nerves containing catecholamine and peptides while the contralateral MCAs showed normal distribution of the nerves. Extracranial occlusion caused no discernible change in the distribution of perivascular nerves in occluded and sham-operated animals. This study indicates that the different methods of cerebral arterial occlusion have variable effects on the perivascular innervation. Arterial occlusion induced by intraluminal or transient extracranial procedures does not impair cerebral perivascular innervation at least up to 3 days post-occlusion. In contrast, cerebral arterial occlusion by extraluminal electrocoagulation diminishes the perivascular nerves around the occluded cerebral artery.

Topics: Animals; Catecholamines; Cerebral Arteries; Cerebral Infarction; Ischemic Attack, Transient; Male; Microscopy, Fluorescence; Nerve Fibers; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Vasoactive Intestinal Peptide

In eight patients carotid angiography was required for evaluation of transient neurological attacks. Cerebral blood flow results, angiography and clinical observations subsequently suggested the diagnosis of migraine. We measured plasma concentrations of substance P(SP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in repeated blood samples obtained from the carotid artery and the internal jugular vein in conjunction with cerebral angiography followed by 4 to 6 repeated recordings of regional cerebral blood flow (rCBF) with the intracarotid Xenon-133 injection technique. This technique is known to induce attacks of migraine with aura in many sufferers. Four patients developed aura symptoms. In three this was succeeded by throbbing headache. Typical, migraine-related, focal hypoperfusion occurred in conjunction with the aura symptoms. The remaining four patients had no symptoms or rCBF changes. There were no systematic or statistically significant changes over time in arterial-venous plasma concentrations or in the release rates of any of the peptides. All migraineurs had an overall elevated mean CGRP value compared to control values from the literature. The overall plasma levels of the potent vasoconstrictor NPY were higher (p < 0.10) in the group that developed symptoms and rCBF changes (136 pmol/l) than in the non-symptomatic group (97 pmol/l). The difference in NPY levels could perhaps be associated with the focal rCBF decrease seen in the attack group.

Topics: Adult; Calcitonin; Calcitonin Gene-Related Peptide; Carotid Artery, Internal; Cerebral Angiography; Cerebrovascular Circulation; Female; Hemiplegia; Humans; Ischemic Attack, Transient; Jugular Veins; Male; Middle Aged; Migraine Disorders; Neuropeptide Y; Neuropeptides; Paresthesia; Radionuclide Imaging; Substance P; Vasoactive Intestinal Peptide; Vision Disorders; Xenon Radioisotopes

INTRODUCTION--Cerebral blood vessels are innervated by sympathetic nerve fibres storing neuropeptide Y (NPY), parasympathetic nerves storing acetylcholine, vasoactive intestinal peptide (VIP) and sensory afferent fibres containing calcitonin gene-related peptide (CGRP), substance P (SP) and neurokinin A. In experimental studies on subarachnoid haemorrhage (SAH) there are indications that perivascular peptides are involved. In the present study we have in man measured the levels of NPY, VIP, SP and CGRP in brain vessels of patients that have suffered a fatal SAH and compared this with the levels encountered in subjects that died of an extracerebral cause. MATERIAL AND METHODS--Vessels from patients who have died from SAH or nonSAH were obtained during autopsy performed within 24 hrs after death. The peptides were extracted and fractionated with reversed phase liquid chromatography (HPLC). The levels of NPY, VIP, SP, and CGRP were measured with radioimmunoassay. Vasomotor responses of human cerebral arteries were performed using a sensitive in vitro system. RESULTS--Human cerebral vessels contained NPY, VIP, CGRP and SP which eluted at the same positions as the authentic peptides. The level of CGRP was significantly lower (p < 0.01) in arteries removed from SAH patients as compared to control subjects. The level of SP was not changed, if anything it tended to be increased after SAH. The levels of NPY and VIP were not significantly altered after SAH. In isolated brain vessels alpha-CGRP was a potent vasodilator of arteries precontracted with whole blood, prostaglandin F2 alpha or endothelin. It had a poor effect on vessels precontracted with 60 mM potassium. CONCLUSION--The evidence suggest that the trigemino-cerebrovascular system, storing CGRP and SP, is to a differential degree involved in the pathophysiology of SAH in man and supports the hypothesis of an exhaustion of CGRP as one important factor in the development of late spasm occurring after SAH.

Topics: Adult; Aged; Brain; Calcitonin Gene-Related Peptide; Cerebral Arteries; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Neuropeptide Y; Subarachnoid Hemorrhage; Substance P; Vascular Resistance; Vasoactive Intestinal Peptide; Vasomotor System

Time-dependent changes in the tissue concentration of tyrosine hydroxylase (TH), adrenaline (A), noradrenaline (NA), and neuropeptide Y (NPY) in the early stages of cerebral ischemia were studied immunohistochemically in the amygdaloid complex of rats subjected to 1 h cerebral ischemia. Immunoreactivity to TH on the lesioned side reached a nadir at 12 h after cerebral ischemia, then gradually increased over 24 h to normal reactivity, but TH immunoreactivity between the ischemic side and the contralateral side was no different for up to 12 h after ischemia. The blood concentrations of NA and A were elevated to about twice the control concentration 12 h after ischemia, then gradually decreased back to normal. NPY immunoreactivity of both sides did not change for up to 6 h after ischemia, but NPY immunoreactivity on the lesioned side decreased over 12 h and maintained a plateau. These findings suggest that responses to cerebral ischemia between catecholamines and peptides are varied.

Topics: Animals; Epinephrine; Immunoenzyme Techniques; Ischemic Attack, Transient; Neuropeptide Y; Norepinephrine; Radioimmunoassay; Rats; Rats, Wistar; Time Factors; Tyrosine 3-Monooxygenase; Vasomotor System

Immunoreactivity for vasoactive peptides [endothelin (ET); calcitonin gene-related peptide (CGRP); atrial natriuretic peptide (ANP); neuropeptide Y (NPY)] was investigated in nervous tissue of Mongolian gerbils in which the common carotid artery (CCA) was temporarily occluded (30 min-4 h) on one side, provoking transient unilateral ischemia at the forebrain level. Observations were carried out in a group of animals that were perfused promptly after CCA reopening, and in a group of animals that were perfused 12 h later. In animals of the first group, darker immunostaining was usually observed for most peptides in the forebrain ipsilateral to the CCA occlusion. Computer-assisted densitometric analysis showed that the asymmetry was relevant for ET, CGRP, and ANP, and almost undetectable for NPY. In animals of the second group, areas of tissue degeneration were observed. In these areas, ET immunoreactivity was markedly denser, whereas immunoreactivity for the remaining peptides was about at the background level. It is concluded that ischemia induces an increase in both vasoconstrictor and vasodilator peptides that in areas of moderate ischemia might maintain a residual tissue perfusion. In areas of severe hypoxia, a predominant ET-induced vasoconstriction would contribute to tissue damage.

Topics: Animals; Atrial Natriuretic Factor; Brain Chemistry; Calcitonin Gene-Related Peptide; Carotid Arteries; Endothelins; Fluorescent Antibody Technique; Gerbillinae; Ischemic Attack, Transient; Neuropeptide Y

The cause of cerebral vasospasm after subarachnoid hemorrhage (SAH) remains unknown. Recently, an association between the potent vasoconstricting peptide, neuropeptide Y, and delayed cerebral vasospasm after SAH has been postulated. This was based on the findings of increased neuropeptide Y levels in the cerebrospinal fluid (CSF) and plasma after SAH in animals and humans. For this study, the primate model of SAH was used to assess the possible role of neuropeptide Y in delayed vasospasm after SAH. Fifteen cynomolgus monkeys underwent placement of a clot of either whole blood or red blood cells in the subarachnoid space around the middle cerebral artery (MCA). Sequential arteriography for assessment of MCA diameter and sampling of blood and CSF for neuropeptide Y were performed: before SAH (Day 0); 7 days after SAH, when signs of delayed cerebral vasospasm peak in this model and in humans; 12 days after SAH; and 28 days after SAH. Subarachnoid hemorrhage did not evoke changes in CSF or plasma levels of neuropeptide Y. Nine monkeys had arteriographic evidence of vasospasm on Day 7, but no change in neuropeptide Y levels occurred in plasma or CSF. In addition, neuropeptide Y levels did not change, even after resolution of vasospasm on Day 12 or Day 28. Neuropeptide Y levels were substantially higher in CSF than in arterial plasma (p less than 0.003 at each interval). No correlation was found between neuropeptide Y levels in CSF and in plasma. These results do not confirm a relationship between neuropeptide Y levels in the CSF or peripheral plasma and delayed cerebral vasospasm in SAH.

Topics: Analysis of Variance; Animals; Cerebral Angiography; Disease Models, Animal; Female; Ischemic Attack, Transient; Macaca fascicularis; Male; Neuropeptide Y; Radioimmunoassay; Subarachnoid Hemorrhage

Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p less than 0.01). CBF returned to preischemic levels approximately 45 min after reperfusion and was reduced to approximately 65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p less than 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p less than 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 nM; 50 microliters) to the middle or posterior temporal branch of the MCA 10-14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (PaCO2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to red

Topics: Adenosine Triphosphate; Animals; Calcitonin Gene-Related Peptide; Capsaicin; Cats; Cerebrovascular Circulation; Female; Ganglionectomy; Hyperemia; Ischemic Attack, Transient; Male; Nerve Fibers; Neuropeptide Y; Pia Mater; Substance P; Trigeminal Ganglion; Vasoactive Intestinal Peptide

A possible role of platelet-derived 5-HT was examined concerning the pathogenesis of cerebral vasospasm. Intracisternal injection of 5 ml of platelet-rich plasma (PRP; approximately 7.5 x 10(8) platelets) induced not only acute (1 h) but also chronic (7 days) angiographically evident cerebral vasospasm in dogs. Sympathetic perivascular nerves on cerebral arteries showed no remarkable change following repeated injections of PRP, as the dense distribution of catecholamine-fluorescence and neuropeptide Y-like immunoreactive nerve fibers on Day 7 was comparable to findings in the preinjection controls. While there were no 5-HT-immunoreactive fibers in the cerebral arteries of control animals, numerous 5-HT-immunoreactive fibers were present in the PRP-injected animals. These results suggest that 5-HT, presumably released from extravasated platelets, may be taken up by nerve endings and act as a vasoconstrictor transmitter in the pathogenesis of chronic vasospasm.

Topics: Acute Disease; Animals; Basilar Artery; Blood Platelets; Catecholamines; Chronic Disease; Dogs; Female; Immunohistochemistry; Ischemic Attack, Transient; Male; Muscle, Smooth, Vascular; Neurons; Neuropeptide Y; Serotonin; Subarachnoid Hemorrhage

The involvement of noradrenaline (NA), neuropeptide Y, (NPY), 5-hydroxytryptamine (5-HT), acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) has been examined in the late phase of spasm after an experimental subarachnoid hemorrhage (SAH) in a rat model. Immunocytochemistry and radioimmunoassay of blood vessels from the circle of Willis did not show significant differences in NPY- and VIP-like immunoreactivity 2 days post SAH as compared to control vessels. The postjunctional effects of NA, NPY, 5-HT, ACh and VIP were studied two days after SAH using a sensitive in vitro system. NPY induced contractions were significantly (p less than 0.01) weaker (lower Emax) in SAH as compared to control rats while the relaxant responses to ACh and VIP were slightly increased after SAH. These observations reveal that in a rat model of SAH, with an approximately 20% in vivo constriction at two days, dynamic changes occur in cerebral artery reactivity despite any obvious change in sympathetic or parasympathetic perivascular nerve networks.

Topics: Acetylcholine; Animals; Basilar Artery; Fluorescent Antibody Technique; Ischemic Attack, Transient; Male; Neuropeptide Y; Norepinephrine; Radioimmunoassay; Rats; Rats, Inbred Strains; Serotonin; Subarachnoid Hemorrhage; Vasoactive Intestinal Peptide; Vasoconstriction

In the present study we investigated the relative vulnerability of neuronal subsets in the striatum to ischemia that was induced by bilateral transient ligation of the common carotid arteries in gerbils. After 4 days of survival, brains were evaluated using histochemical methods (NADPH-diaphorase and silver degeneration procedures) and neurochemical methods with radioimmunoassays for somatostatin-, neuropeptide Y-, and substance P-like immunoreactivity and measurements of amino acids using high-pressure liquid chromatography with electrochemical detection. NADPH-diaphorase-positive neurons were strikingly preserved in the ischemic dorsolateral portion of the striatum, in which there was severe neuronal loss. There was no significant depletion of NADPH-diaphorase-positive neurons in the striatum or cerebral cortex. Concentrations of neuropeptide Y-like and somatostatin-like immunoreactivity were unchanged despite a significant 25% depletion of substance P-like immunoreactivity and gamma-aminobutyric acid. Ischemic brain damage may be mediated by a neurotoxic effect of glutamate acting at the N-methyl-D-aspartate (NMDA) receptor. Previous studies of NMDA excitotoxin lesions in rat striatum have shown a sparing of neurons containing NADPH-diaphorase, somatostatin, and neuropeptide Y. The similar sparing of these neurons following ischemic lesions in gerbil striatum provides further evidence that NMDA receptor activation may play a role in ischemic injury.

Topics: Animals; Corpus Striatum; Gerbillinae; Ischemic Attack, Transient; NADH, NADPH Oxidoreductases; NADPH Dehydrogenase; Neuropeptide Y; Radioimmunoassay; Somatostatin

The effects of transient (30') forebrain ischemia (4 vessel occlusion model) on peptidergic neurons and astroglial cells in various diencephalic and telencephalic areas have been analyzed. The study was performed at various time intervals of reperfusion, i.e. 4 h, 1, 7 and 40 days. Neuropeptide Y (NPY), somatostatin (SRIF), cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP) and arginine-vasopressin (AVP) immunoreactive (IR) neuronal systems and glial fibrillary acidic protein (GFAP)-IR glial cells have been visualized by means of the indirect immunoperoxidase procedure using the avidin-biotin technique. The analysis was performed by means of computer assisted microdensitometry and manual cell counting. At the hippocampal level a huge reduction of neuropeptide (CCK, SRIF, VIP) IR cell bodies was observed, still present 40 days after reperfusion. On the contrary, in the frontoparietal cortex the number of the neuropeptide (CCK, SRIF, VIP, NPY) IR neurons showed a decrease at 4 h, 1 and 7 days after reperfusion followed by a complete recovery at 40 days. A rapid reduction followed by an almost complete recovery (7 days after reperfusion) was also observed at striatal level where SRIF- and NPY-IR neurons were detected. A marked decrease of NPY-IR terminals was observed in the paraventricular and periventricular hypothalamic nuclei and in the paraventricular thalamic nucleus. AVP-IR was markedly reduced in the magnocellular part of the paraventricular nucleus throughout the analyzed period (7 days after reperfusion). GFAP-IR was increased in the hippocampal formation and neostriatum while a not consistent increase was observed at neocortical level. These data point to a differential recovery of peptide-IR and to a different astroglial response in the various brain areas after transient forebrain ischemia. Region-specific factors rather than factors related to neuronal chemical coding seems to play a major role in determining the vulnerability of neuronal populations to transient ischemia.

Topics: Animals; Arginine Vasopressin; Astrocytes; Cerebral Cortex; Cholecystokinin; Corpus Striatum; Electroencephalography; Glial Fibrillary Acidic Protein; Hippocampus; Immunohistochemistry; Ischemic Attack, Transient; Male; Neurons; Neuropeptide Y; Peptides; Rats; Rats, Inbred Strains; Somatostatin; Vasoactive Intestinal Peptide

NPY is a putative neurotransmitter mainly co-localized with noradrenaline in sympathetic fibers which innervate the cerebral vasculature. The origin of most of the perivascular NPY fibers seems to be in the superior cervical ganglion. To investigate involvement of Neuropeptide Y (NPY) mechanisms in subarachnoid haemorrhage (SAH), twenty patients with SAH were investigated. NPY-LI (-like immunoreactivity) levels in the external jugular vein were assessed using radioimmunoassay in blood samples collected post-operatively (or after SAH in non-surgical patients) on days 1,2,3, 5,7 and 9. These levels were compared with the clinical course and blood flow velocity changes monitored with ultrasonic Doppler equipment from both middle cerebral arteries (MCA) and both internal carotid arteries (ICA). Compared to NPY-LI levels in 14 controls (mean 116 +/- 3 pmol/1), increased levels (up to 253 pmol/l) and a close relationship between velocities and NPY-LI levels were found in a subpopulation of the SAH patients. When comparing the mean haemodynamic index (V MCA/ipsilateral V ICA) and mean NPY-LI levels in each of the 20 patients, a correlation of r = 0.75, p = 0.0001 was found. Increased NPY-LI were found (131 +/- 8 pmol/l) when simultaneous Doppler velocity recordings showed vasoconstriction (Haemodynamic index greater than 5) compared with samples taken when the haemodynamic index was less than 5, p less than 0.05. When MCA velocity exceeded 120 cm/sec. increased levels were found (129 +/- 9 pmol/l) compared with the conditions when MCA velocity was less than 120 cm/sec (113 +/- 5 pmol/l), p = 0.06. The results indicate a possible NPY involvement in cerebral vasoconstriction after SAH.

Topics: Adult; Aged; Blood Flow Velocity; Cerebrovascular Circulation; Echoencephalography; Female; Follow-Up Studies; Glasgow Coma Scale; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Jugular Veins; Male; Middle Aged; Neuropeptide Y; Radioimmunoassay; Subarachnoid Hemorrhage; Sympathetic Nervous System; Vasoconstriction

Topics: Animals; Blood Pressure; Cerebral Ventricles; Clonidine; Injections, Intraventricular; Ischemic Attack, Transient; Male; Neuropeptide Y; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta

The possible role of neuropeptide Y (NPY) as a vasoconstrictor substance contributing to the development of cerebral vasospasm after experimental subarachnoid hemorrhage was studied. Autologous blood was injected into the cisterna magna of control rabbits and rabbits that had received bilateral superior cervical ganglionectomy 2 days before blood injection. Three days after blood injection the concentration of NPY in cerebrospinal fluid (CSF) was 5971 +/- 551 pg/ml while CSF from control animals contained 992 +/- 162 pg/ml of NPY. The effects of porcine NPY on norepinephrine-induced contraction of rabbit cerebral arteries were also studied in vitro. NPY (1.2 nM) caused a 3-fold potentiation of norepinephrine-induced contraction of cerebral arteries. CSF from control rabbits diluted by 50% with Krebs solution had no significant effect on norepinephrine-induced contraction of cerebral arteries when compared to responses in Krebs solution only; however, diluted CSF from denervated blood-injected rabbits potentiated norepinephrine-induced contraction by 2.6-fold. Antiserum containing NPY specific antibodies was used to immunoprecipitate the peptide from CSF taken from denervated blood-injected rabbits. CSF treated with this antiserum contained less than 40 pg/ml of NPY and had no effect on norepinephrine-induced contraction of cerebral arteries. These results show that the concentration of NPY in CSF of rabbits is elevated after experimental subarachnoid hemorrhage. In addition, NPY in CSF can potentiate the vasoconstrictor effect of norepinephrine which may contribute to the development of cerebral vasospasm.

Topics: Animals; Cerebral Arteries; Ischemic Attack, Transient; Male; Muscle Contraction; Neuropeptide Y; Norepinephrine; Rabbits; Subarachnoid Hemorrhage; Time Factors; Vasoconstrictor Agents

Neuropeptide Y (NPY) has been demonstrated in the human circle of Willis by specific radioimmunoassay. Concentrations were similar in cadaver and peroperative specimens. NPY concentrations were highest around the basilar bifurcation (2.9 +/- 1.0 pmol/g), anterior cerebral artery (2.7 +/- 0.5 pmol/g), and carotid trifurcation (2.4 +/- 0.6 pmol/g). Concentrations were lowest in the basilar artery (1.0 +/- 0.4 pmol/g). Intracarotid administration of NPY (50 pmol to 2 nmol) to rats reduced mean cerebral cortical blood flow by 40-98%. This vasoconstriction lasted for at least 2 h. These findings suggest that NPY may be involved in the cerebral vasospasm which follows subarachnoid haemorrhage and in the maintenance of normal vascular tone.

Topics: Animals; Blood Pressure; Carotid Arteries; Cerebrovascular Circulation; Circle of Willis; Humans; Ischemic Attack, Transient; Male; Nerve Tissue Proteins; Neuropeptide Y; Radioimmunoassay; Rats; Rats, Inbred Strains