High-flow angiopathy: cerebral blood vessel changes in experimental chronic arteriovenous fistula.

Profound vascular damage secondary to high-flow extracranial states has been well characterized. However, changes in cerebral vasculature secondary to high-flow states have not been studied. To determine changes related to high-flow states in cerebral vessels, a rabbit model was developed in which torrential flow was created in the vertebrals, carotids, basilar, and vessels of the circle of Willis by means of a carotid-jugular shunt after ligation of the proximal carotid. The clinical, angiographic, and histologic changes noted in the animal model include: abrupt clinical deterioration after a variable interval with some animals developing ptosis, afferent vessel dilatation and the development of prominent anastomotic channels, variable cerebral vessel histopathology--related to duration and relative proximity to the shunt--affecting all three vessel layers, plump, irregular, and clumped endothelium, denuded with adherent platelets, irregular, duplicated, and thinned internal elastic membrane, frayed with invasion of the intima by mesenchymal cells, vacuolization and necrosis of the media muscle, and invasion of adventitia by foreign cells and small blood vessels. The high-flow angiopathy seen in this model may help explain vascular changes associated with high-flow cerebral vascular lesions, as well as other types of vascular damage.

Amygdalospinal projections in the cat.

Spinal cord injections of rhodamine-labeled fluorescent latex microspheres in the cat resulted in retrograde labeling of a dense, well-defined group of neurons within the central nucleus of the amygdala and a modest number of neurons in the medial nucleus. Amygdalospinal neurons were found to be large cells of variable shape and orientation that were distributed bilaterally with an ipsilateral predominence.

Limbic influence on the periaqueductal gray: a single unit study in the awake squirrel monkey.

Single neurons of the periaqueductal gray (PAG) were studied during electrical stimulation of the amygdala and hippocampus. Fifty-one percent (34/67) of the units sampled throughout the rostrocaudal extent of the PAG were found to have a limbic influence. PAG neurons were characterized by low spontaneous firing rates (means = 4.94 spikes/sec). Units responded to basolateral amygdala stimulation primarily with short duration excitatory responses having a mean latency of 30 ms (range: 13.3-110 ms). Responses to corticomedial and lateral amygdala stimulation produced different patterns of activation including complex excitatory and inhibitory sequences. Only 10 units (15%) sampled in PAG responded to hippocampal stimulation with excitatory or tonic-inhibitory responses. The majority of responsive units (8) were to anterior hippocampal stimulation (latency range: = 20-75 ms). High frequency (9 Hz) basolateral amygdala stimulation recruited responses with increases in the probability of firing and a decrease in initial latency and latency variability.

Pontomedullary raphe neurons: intracellular responses to central and peripheral electrical stimulation.

The responses of pontomedullary raphe neurons to electrical stimulation of the medullary reticular formation (MRF) and the mesencephalic ventral periaqueductal gray region (PAG) were studied using intracellular methods in chloralose-anesthetized cats. Single shock stimulation of PAG at the level of the trochelear nucleus evoked short latency, monosynaptic excitatory postsynaptic potentials (EPSPs) in antidromically identified raphe-spinal neurons. Similar large EPSPs were produced by medullary reticular stimulation of either side. The large majority of raphe-spinal neurons responded to sciatic nerve shock, and most responded to tooth pulp or forepaw shock as well; these responses were always bilateral. The responses of cells that could not be antidromically invaded from spinal cord were similar to those of raphe-spinal neurons, but tended to be more variable. Intracellular injection of horseradish peroxidase into electrophysiologically characterized cells revealed that most recordings were made from large and medium sized raphe neurons. These findings are discussed in the context of a potential role for pontomedullary raphe neurons in nociception.

Edinger-Westphal neurons that project to spinal cord contain substance P.

Combined retrograde transport and immunocytochemical methods were used to determine whether Edinger-Westphal neurons projecting to spinal cord also demonstrate substance P-like immunoreactivity (SPLI). Large injections of horseradish peroxidase (HRP) into cervical and lumbar enlargements retrogradely labeled cells throughout the length of the Edinger-Westphal complex (EW). Nearly all HRP-labeled EW neurons also stained for SPLI, evidence that EW is the origin of a direct substance P pathway linking rostral mesencephalon with spinal cord.

Central hypotensive action of alpha-methyldopa: an iontophoretic study in the cat.

The central site and mechanism of alpha-methyldopa-induced hypotension were examined with the microiontophoretic technique which permits the topical application of drugs to single neurons of the bulbar vasomotor center in decerebrate cats. Cardiovascular neurons were identified by their response to an increase in arterial blood pressure following a small intravenous pressor dose of norepinephrine. Microiontophoretic application of alpha-methyldopa was found to have an inhibitory effect on the spontaneous firing rate of cardiovascular neurons. Furthermore, alpha-methyldopa was found to completely block the excitatory response of cardiovascular neurons to iontophoretically applied norepinephrine. Non-cardiovascular neurons, recorded from the same brain area, were unaffected by iontophoretic application of alpha-methyldopa at the same or greater doses that produced responses in cardiovascular neurons. While peripheral factors cannot be entirely ruled out, the present findings are contrary to the postulate that alpha-methyldopa lowers arterial blood pressure by stimulating central alpha-adrenoceptors, causing a reduction of sympathetic outflow to the periphery. Rather, the data indicate that alpha-methyldopa or its metabolites act directly on central alpha-adrenoceptors in a manner which results in reduced activity.

CNS site of clonidine induced hypotension: a microiontophoretic study of bulbar cardiovascular neurons.

To localize the central site and mechanism of clonidine induced hypotension, the drug was applied by the technique of microiontophoresis to neurons of the bulbar cardiovascular center in decerebrate cats. The excitatory and inhibitory cardiovascular neurons (CVN) were identified by their response to an increase in the arterial blood pressure induced by intravenous injections of small doses of norepinephrine (NE). Clonidine had an inhibitory effect on the spontaneous firing rate of excitatory CVN but had no effect on the firing rate of inhibitory CVN. At the same doses, it had no effect on the firing rate of NCVN recorded from the same area. Furthermore, clonidine had a blocking action on the excitatory response of CVN induced by microiontophoretic application of NE. It is concluded that clonidine produces its hypotensive response by acting on alpha-adrenergic receptors of bulbar CVN.

Electro-acupuncture analgesia in monkeys: a behavioral and neurophysiological assessment.

Monkeys were initially trained to press a lever to escape noxious electrical stimulation applied to one leg. They were then presented with electrical stimuli consisting of 40 successive intensity increments beginning at zero intensity and with random interstimulus intervals (ISIs). A lever press, initiated by the monkey during presentation of a stimulus, immediately terminated stimulation of the leg, triggering another sequence of the same increasing stimuli with a new series of ISIs. After establishment of a stable threshold measure of lever pressing, 45 min of electro-acupuncture was applied to traditional points on both legs. The results show that electro-acupuncture dramatically increased (300-400 %) the lever pressing threshold for approximately 20 min after electro-acupuncture stimulation was terminated. In acute monkey preparations, spike activity of single neurons in N. Parafascicularis of the thalamus, evoked by noxious electrical stimulation to the sciatic nerve, was recorded. The evoked activity of only nociceptive specific neurons was either eliminated or markedly reduced for at least one hour following 45 min of electro-acupuncture applied to traditional points on both legs. The observations made by these two experimental approaches suggest that electro-acupuncture exerts an analgesic effect on artificially induced nociception.