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Biomedical subjects

M A Moskowitz

Publications and source records attributed to M A Moskowitz.

At least 325 records · Page 18Linked to original sources
PubMed1984

Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry.

Anatomical and clinical observations suggest that supratentorial vascular structures contain afferent projections from the trigeminal ganglia. To characterize this innervation, horseradish peroxidase (HRP) and HRP conjugated to wheat germ agglutinin were applied to the pial and dural arteries and sinuses of 33 cats. HRP was restricted to the site of interest by applying it dissolved in a viscous polymer, polyvinyl alcohol (PVA), to achieve slow release and minimize diffusion. The ganglia of cranial nerves V, VII, IX, and X and the superior cervical ganglia (SCGs) were examined bilaterally for the presence of retrogradely transported protein. Horseradish peroxidase applied to the proximal middle cerebral artery was located in cell bodies occupying the portion of the ipsilateral trigeminal ganglion corresponding to the ophthalmic division and throughout both SCGs. When the tracer was applied to the right anterior or posterior superior sagittal sinus, HRP-positive cells were present as above, predominantly in the ipsilateral trigeminal ganglia corresponding to the ophthalmic division and throughout both SCG. When applied to the right middle meningeal artery, HRP was observed within neurons of ipsilateral SCG and in the ophthalmic division of trigeminal ganglia; a few enzyme-containing cells were present in ipsilateral regions corresponding to the second and third divisions. These observations support the concept that supratentorial vascular structures receive afferent nervous projections from trigeminal neurons.

Afferent Pathways↗
PubMed1984

The neurobiology of vascular head pain.

Nervous connections between the trigeminal ganglia and cerebral blood vessels have recently been identified in experimental animals and have been termed the trigeminovascular system. Existence of this system in humans is inferential. Trigeminovascular neurons and their peripheral unmyelinated nerve fibers contain the neurotransmitter peptide substance P. Most newly synthesized substance P is transported from ganglion cell bodies to afferent nerve fibers, where depolarization-induced release of neurotransmitter into the wall of the cerebral blood vessel occurs. Substance P dilates pial arteries, increases vascular permeability, and activates cells that participate in the inflammatory response. The relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.

Afferent Pathways↗
PubMed1984

Vasoactive intestinal polypeptide and acetylcholine are responsible for neurovasodilation in the head of the cat.

There is reason to believe that the dilator innervation to blood vessels of many of the tissues of the head may be part of a common outflow from the central nervous system. Part of the effect of its activation is due to the release of acetylcholine and evidence is presented that, in addition, vasoactive intestinal polypeptide (VIP) release also plays a role. The non-cholinergic part of the dilator response to nerve activity can in a series of blood vessels be correlated with the level of VIP in their wall and is selectively reduced by VIP antiserum. In addition, VIP has suitable characteristics as a vasodilator. Whereas substance P which is present in the walls of many arteries of the head, does not qualify as a putative dilator transmitter. Despite the fact that the physiological role of dilator innervation to the circulation as a whole is not understood, the powerful consequences of the activation of the system in particular blood vessels suggests that this innervation should be seriously considered when studying the regulation of peripheral resistance.

Acetylcholine↗
PubMed1984

Inhibition of stimulated prostaglandin biosynthesis by retinoic acid in smooth muscle cells.

Bovine aorta smooth muscle cells (SMC) incubated with a tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), released increased levels of prostaglandin I2 [measured as its stable hydrolytic product, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha)], and this response was inhibited by all-trans-retinoic acid (RA) at concentrations as low as 17 nM. Retinol and retinyl acetate, at concentrations as high as 1.7 and 1.5 microM, respectively, did not inhibit the TPA-stimulated 6-keto-PGF1 alpha production. RA was not cytotoxic at 1.7 microM, as assayed by exclusion of trypan blue dye. Inhibition by RA was increased after preincubation of the SMC with RA prior to TPA stimulation. The inhibition of arachidonic acid (AA) metabolism by RA was not specific for TPA stimulation; RA inhibited prostaglandin production after SMCs were stimulated by serotonin; melittin; the Ca2+ ionophore, A23187; and fetal calf serum. RA had no effect on phorbol ester binding to SMC, nor did it inhibit increased 6-keto-PGF1 alpha production in SMC treated with exogenous AA. While RA inhibited TPA-stimulated production of 14C-labeled 6-keto-PGF1 alpha from [14C]AA-labeled cells, it did not inhibit the accumulation of [14C]AA in the culture medium. The data suggest that RA inhibits stimulated, rather than basal, levels of prostaglandin production. RA does not seem to act by inhibiting the deacylation of AA from cellular phospholipid pools, insofar as this is reflected in the accumulation of AA in the media, but may inhibit reactions at, or after, the generation of endoperoxides by cyclooxygenase.

Animals↗
PubMed1983

Do intracranial and extracranial trigeminal afferents represent divergent axon collaterals?

Trigeminal nerves provide the principal afferent pathways for the transmission of intracranial and extracranial head pain. This study, using two retrograde axonal tracers, demonstrated that first division afferents projecting to intracranial and extracranial targets are not commonly axon collaterals of the same neuron. Therefore, divergent axon collaterals probably are not responsible for the phenomenon of referred pain within the first trigeminal division.

Afferent Pathways↗
PubMed1983

Pia arachnoid contains substance P originating from trigeminal neurons.

Immunoreactive substance P is present in measurable amounts in pia arachnoid from rat, cat, dog and calf. Levels of substance P in this tissue are comparable to those found in peripheral structures receiving innervation from dorsal root or trigeminal ganglia. Separation and measurement of bovine pia-arachnoid extract by reverse phase high performance liquid chromatography and radioimmunoassay reveals a single peak of activity with a retention time identical to that of substance P. Unilateral lesions of the trigeminal ganglia decrease substance P levels within cat pia arachnoid and accompanying blood vessels ipsilaterally by greater than 50%. These data indicate that most of the substance P surrounding pial blood vessels resides within afferent nerve fibres from trigeminal ganglion cells.

Animals↗
PubMed1983

In vitro release of immunoreactive substance P from putative afferent nerve endings in bovine pia arachnoid.

The release of substance P-like immunoreactivity was examined using bovine pia arachnoid and its attendant blood vessels in vitro. At concentrations of 20,51, and 100 mM, potassium ions evoked the release of substance P-like immunoreactivity in a dose-dependent manner. The drug capsaicin released substance P at concentrations greater than 10(-8) M. Both potassium- and capsaicin-induced release were abolished by omitting calcium ions from the superfusion buffer. When subjected to separation by reverse phase high performance liquid chromatography, the superfusate from capsaicin perfused tissues contained a peak of immunoreactivity which migrated at the retention time corresponding to substance P. During basal and stimulated states, the percent endogenous substance P released ranged between 0.4-6.5 X 10(-2) and 1.3-11.6 X 10(-2) per minute, rates comparable to those previously reported by others using slices of dorsal horn or spinal cord segments. The immunoreactivity measurable in the conditioned buffer probably reflected release from afferent nerve endings in as much as most of the substance P immunoreactivity in pia arachnoid arises from trigeminal ganglia. Release of substance P, a cerebrovasodilating peptide from perivascular nerve endings in pia arachnoid suggests a possible role for substance P in the pathophysiology of disorders associated with pain of cerebrovascular origin.

Animals↗
PubMed1982

Conditioned media from activated lymphocytes maintain sympathetic neurons in culture.

Nerve growth factor (NGF) is vital for the development and maintenance of sympathetic neurons. In the present report, we demonstrate that NGF maintenance activity can be substituted by lymphoid cells. Indeed, coculturing lymphoid cells with sympathetic neurons in the absence of exogenous NGF resulted in neuronal survival, as measured by morphological and biochemical criteria. In addition, conditioned media from concanavalin A-activated lymphoid cells could replace NGF. The lymphoid secreted factor differs from NGF in its inability to induce neuronal differentiation, and in its lack of cross-reactivity with NGF in radioimmunoassays. We thus discovered a potential novel source for a factor essential for neuronal survival.

Animals↗
PubMed1981

Perivascular meningeal projections from cat trigeminal ganglia: possible pathway for vascular headaches in man.

Peroxidase-containing cell bodies were found in the ipsilateral trigeminal ganglia after horseradish peroxidase was applied to the proximal segment of the middle cerebral artery in seven cats. Cell bodies containing the enzyme marker were located among clusters of cells that project via the first division. The existence of sensory pathways surrounding large cerebral arteries provides an important neuroanatomical explanation for the hemicranial distribution of headaches associated with certain strokes and migraine.

Afferent Pathways↗
PubMed1981

Serotonin receptor-mediated stimulation of bovine smooth muscle cell prostacyclin synthesis and its modulation by platelet-derived growth factor.

Serotonin (5-hydroxytryptamine; 0.5 microM and above) stimulated the synthesis of prostacyclin (as measured by radioimmunoassay of 6-ketoprostaglandin F1 alpha) by bovine aortic smooth muscle cells in culture. This effect was structurally specific; a similar response was not elicited by the other indoles (tryptophan, n-acetylserotonin, 5-hydroxytryptophan, melatonin, or 5-hydroxyindoleacetic acid) or by the amines phenylephrine, isoproterenol, dopamine, or histamine). The response was reversible and was saturable at serotonin concentrations of 10 microM or higher. An increase in prostacyclin synthesis was elicited by the addition of a serotonin agonist, quipazine (1 microM and above), and antagonized by the serotonin receptor blockers cyproheptadine, methysergide, or methiothepin but not by other aminergic receptor-blocking drugs (e.g., phentolamine or propranolol). This effect was selective for cell type because serotonin or quipazine (100 microM) did not increase prostacyclin synthesis by bovine aortic endothelial cells. The addition of platelet-derived growth factor (PDGF) to cultures of smooth muscle cells dramatically enhanced prostacyclin synthesis in response to the coadministration of serotonin. PDGF greatly increased the maximum response to serotonin without altering the half-maximal effective concentration for serotonin. This synergistic interaction was blocked by the addition of a serotonin-receptor blocking agent. Taken together, these data suggest that serotonin stimulates smooth muscle prostacyclin synthesis through a specific receptor-mediated mechanism that can be modulated by PDGF.

Animals↗
PubMed1981

Protein synthesis in rat brain microvessels decreases with aging.

The synthesis of protein by brain microvessels prepared from rats 4, 15, and 21 months of age was examined in organ culture. The rate of [35S]methionine incorporation into trichloroacetic acid-insoluble protein was lower in the vessels from older animals. These decreases were not dependent on the concentration of added methionine. Differences in protein synthesis could not be accounted for by specific peptidases in the incubation mixture. Polypeptide bands corresponding to actin and to the heavy and light chains of myosin were observed among the newly synthesized proteins following electrophoresis and autoradiography of the incubation mixture on polyacrylamide gels. The pattern of proteins synthesized, however, did not appear to vary significantly between young and old animals. Age-related decreases in the synthesis of vascular proteins may contribute, in part, to some of the changes in the mechanical and functional properties of blood vessels during aging.

Aging↗
PubMed1980

Platelet-dependent stimulation of prostacyclin synthesis by platelet-derived growth factor.

Prostacyclin (PGI2), an unstable metabolite of arachidonic acid synthesized by vascular endothelial and smooth muscle cells, is a potent vasodilator and endogenous inhibitor of platelet aggregation. Regulation of PGI synthesis by the vessel wall is not well understood. We have investigated the possibility that a product released from platelet granules during degranulation might modify vessel wall PGI2 biosynthesis. We report here that a non-dialysable, platelet-dependent factor in serum dramatically stimulates PGI2 synthesis by cultured bovine aortic endothelium aortic smooth muscle, and adrenal capillary endothelium. Platelet-derived growth factor (PDGF), a releasable peptide contained within platelet alpha granules, stimulates PGI2 synthesis by the above cell types as much as 100-fold. The concentrations of PDGF required to produce these effects are below the level reported in normal human serum. We postulate that in vivo released PDGF may increase vessel wall PGI2 production as part of a negative feedback mechanism controlling platelet aggregation.

Animals↗