Triptans disrupt brain networks and promote stress-induced CSD-like responses in cortical and subcortical areas.

A number of drugs, including triptans, promote migraine chronification in susceptible individuals. In rats, a period of triptan administration over 7 days can produce "latent sensitization" (14 days after discontinuation of drug) demonstrated as enhanced sensitivity to presumed migraine triggers such as environmental stress and lowered threshold for electrically induced cortical spreading depression (CSD). Here we have used fMRI to evaluate the early changes in brain networks at day 7 of sumatriptan administration that may induce latent sensitization as well as the potential response to stress. After continuous infusion of sumatriptan, rats were scanned to measure changes in resting state networks and the response to bright light environmental stress. Rats receiving sumatriptan, but not saline infusion, showed significant differences in default mode, autonomic, basal ganglia, salience, and sensorimotor networks. Bright light stress produced CSD-like responses in sumatriptan-treated but not control rats. Our data show the first brain-related changes in a rat model of medication overuse headache and suggest that this approach could be used to evaluate the multiple brain networks involved that may promote this condition.

Analogous responses in the nucleus accumbens and cingulate cortex to pain onset (aversion) and offset (relief) in rats and humans.

In humans, functional magnetic resonance imaging (fMRI) activity in the anterior cingulate cortex (ACC) and the nucleus accumbens (NAc) appears to reflect affective and motivational aspects of pain. The responses of this reward-aversion circuit to relief of pain, however, have not been investigated in detail. Moreover, it is not clear whether brain processing of the affective qualities of pain in animals parallels the mechanisms observed in humans. In the present study, we analyzed fMRI blood oxygen level-dependent (BOLD) activity separately in response to an onset (aversion) and offset (reward) of a noxious heat stimulus to a dorsal part of a limb in both humans and rats. We show that pain onset results in negative activity change in the NAc and pain offset produces positive activity change in the ACC and NAc. These changes were analogous in humans and rats, suggesting that translational studies of brain circuits modulated by pain are plausible and may offer an opportunity for mechanistic investigation of pain and pain relief.

Structural heterogeneity of apoB-containing serum lipoproteins visualized using cryo-electron microscopy.

Cryo-electron microscopy was used to analyze the structure of lipoprotein particles in density gradient subfractions of human very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL). Lipoproteins from a normolipidemic subject with relatively large and buoyant LDL (pattern A) and from a subject with a predominance of small dense LDL (pattern B) were compared. Projections of VLDL in vitreous ice were heterogeneous in size, but all were circular with a relatively even distribution of contrast. Selected projections of LDL, on the other hand, were circular with a high density ring or rectangular with two high density bands. Both circular and rectangular LDL projections decreased in average size with increasing subfraction density, but were found in all of 10 density gradient subfractions, both in pattern A and in pattern B profiles. Preparations of total IDL contained particles with the structural features of VLDL as well as particles resembling LDL. IDL particles resembling LDL were observed in specific density gradient subfractions in the denser region of the VLDL;-IDL density range. Within the group of IDL particles resembling LDL considerable heterogeneity was observed, but no structural features specific for the pattern A or pattern B lipoprotein profile were recognized. The observed structural heterogeneity of the apolipoprotein B-containing serum lipoproteins may reflect differences in the composition of these particles that may also influence their metabolic and pathologic properties.

Increased calcium/calmodulin protein kinase activity in astrocytes chronically exposed to ethanol: influences on glutamate transport.

The effects of ethanol exposures on calcium/calmodulin-dependent protein kinase activity as well as its influence on glutamate uptake were determined in astrocytes prepared from neonatal rat cerebral cortex. Acute 15-min exposure to 100 mM ethanol had no effect on Ca2+/CaM-dependent protein kinase activity. However, chronic exposure to 100 mM ethanol for 4 days elicited a significant increase in the activity of this enzyme with no parallel increase in its expression. Ca2+/CaM-independent kinase activity was less than 1% of the Ca2+/CaM-dependent kinase activity and was unaffected by any of the ethanol exposures. Exposure to 100 mM ethanol for four days also resulted in a significant increase in Na+-dependent [3H]glutamate uptake which was reversed when ethanol-exposed astrocytes were co-incubated with KN-93, a specific inhibitor of Ca2+/CaM kinase. These results suggest that the effects of ethanol on glutamate transport may be mediated in part, by the level of Ca2+/CaM kinase activity.

Origin of the v. portae and variability of its tributaries in laboratory animals. VI. The laboratory mouse (Mus musculus var. alba).

The authors studied the origin and variability of the tributaries of the v. portae in 30 adult laboratory mice (Mus musculus var. alba) of both sexes, after first injecting the portal bed with bluedyed latex. In 19 cases (63.3%) the v. portae was formed by the union of three tributaries and in 11 cases (36.7%) by the union of four to eight. The v. mesenterica cranialis was a constant tributary in every case (100%). The v. lieanalis was a tributary in 27 cases (90.0%) and the next most frequent tributary was the v. pancreaticoduodenalis (14 cases--46.7%) A v. gastrica sinistra was found in every case (100.0%), in 24 cases (80.0%) it joined the v. lienalis and in the other six (20.0%) it was a direct tributary of the v. portae. A v. cardiaca was also observed in every case (100%). In 28 cases (93.3%) it was a tributary of the v. gastrica sinistra and in the remaining two (6.7%) it was a direct tributary of the v. portae. A v. pylorica was found in 27 mice (90.0%). Most often it was a tributary of the v. gastroepiploica dextra (11 cases--36.7%) or the v. gastrica sinistra (9 cases--30.0%). In only one case was it a direct tributary of the v. portae. A v. pancreaticoduodenalis cranialis was present in a total of 28 cases (93.3%). In 12 cases (40.0%) of already originated in the region of the cauda pancreatis and in 16 cases (53.3%) it arose only from the corpus and caput pancreatis.(ABSTRACT TRUNCATED AT 250 WORDS)

Variability of the v. cava caudalis and its tributaries in some laboratory animals. II. The laboratory rat (Rattus norvegicus v. alba).

Duplication of the v. renalis was found in 11 of the regions examined (18.3%), when it was more frequent on the right side. A v. capsularis was found in 35 regions (58.3%), usually as a single vein. There were 1-3 vv. suprarenales (but mostly two; on the right they usually joined the v. cava caudalis and on the left the v. renalis sinistra). A v. spermatica was present on the right side in every case, but on the left side in 11 cases only; in one case it was duplicated. In the rat, the v. spermatica was rather thin; if absent, it was replaced by the v. deferentialis. In nine cases (60.0%) the v. uterina cranialis dextra opened into the v. cava caudalis, while in 12 cases (80.0%) the left vein opened into the v. renalis sinistra. A v. uterina media, draining blood from the caudal third of the cornu uteri, was found in only five cases (16.7%). The v. uterina caudalis drained blood from the corpus and cervix uteri. The v. ovarica was a constant finding; it was mostly joined by the v. lumbalis--and on the left side by the v. phrenica sinistra. In males, the vv. lumbales occurred mostly as a pair of veins lying just below the vv. renales. In females, they were present on both sides. As a rule, the v. iliolumbalis occurred as a single vein on both sides. The v. cava caudalis originated at the level of the transition between the lumbar and the sacral spine, usually at the confluence of the two vv. iliacae communes, which in 14 cases (46.7%) were joined by the v. sacralis mediana. Duplication of the v. cava caudalis was found in only one case (a female). Comparison of the morphology of the v. cava caudalis and its tributaries in the rat and the guinea pig showed more slight differences between the two species.

Variability of the v. cava caudalis and its tributaries in some laboratory animals. I. The guinea pig (Cavia aperea f. porcellus).

The authors studied variability of the v. caudalis and its tributaries in 30 guinea pigs (Cavia aperea f. porcellus--15 males and 15 females) after injecting the relevant venous system with blue-dyed latex. Since the largest lobe of the guinea pig's liver (the lobus sinister) is situated on the left, the right kidney lies further cranially than the left one. In males, as a rule, the right v. renalis opens into the v. cava caudalis further cranially than the left one. The number of vv. renales showed no sex-related differences, although in 17 regions (i.e. in 29%) there was more than one. The increase most often concerned the v. renalis dextra (the ratio in relation to the left vein was 15:2). The tributaries of the vv. renales are the v. spermatica or v. uterina cranialis a v. lumbalis and a v. or vv. suprarenales. There are usually two tributaries, (the commonest of which is the v. spermatica or v. uterina cranialis) on both the right and the left side, though somewhat more frequently on the left (23:19). Blood is drained from the surface or capsule of the kidney relatively often (in 75% of the cases) by the capsularis, which is the most frequent tributary of the v. spermatica or v. uterina cranialis of the corresponding side. Vv. suprarenales (1-4) are a constant finding on both sides. In males they open more often into the v. cava caudalis and in both sexes they also open into the v. renalis and v. lumbalis. The v. spermatica dextra opened into the v. renalis dextra in 10 cases and the v. spermatica sinistra into the v. renalis sinistra in 12 cases. The v. uterina cranialis dextra was a tributary of the v. renalis dextra in eight cases and the v. uterina cranialis sinistra joined the v. renalis sinistra in 13 cases. Drainage into the v. renalis can thus be regarded as the norm in both sexes and on both sides. The v. uterina caudalis leads from the corpus and cervix uteri and joins the v. uterina cranialis. It has a regular incidence and caudally it is most often a tributary of the v. iliaca communis. The v. ovarica is a constant tributary of the v. uterina cranialis; it is usually joined by several vv. lumbales or v. v. capsulares.(ABSTRACT TRUNCATED AT 400 WORDS)

Origin of the v. portae and variability of its tributaries in laboratory animals. V. The golden (Syrian) hamster (Mesocricetus auratus).

The authors studied the origin and variability of the v. portae in 30 adult golden hamsters (Mesocricetus auratus) of both sexes after injecting blue-dyed latex into their portal bed. In 16 cases (53.3%) the v. portae was formed from three tributaries and in 11 cases (36.7%) from four. The v. mesenterica cranialis was the only constant tributary, the v. lienalis was a tributary in 28 cases (93.3%) and the other most frequent tributaries were the v. gastroduodenalis and the v. pancreaticoduodenalis cranialis. In one case there was an anastomosis between the v. portae and the v. cava caudalis. In 25 cases (83.3%) the v. gastrica sinistra joined the v. lienalis, in four (13.3%) it was an independent tributary of the v. portae and in one case (3.3%) it was duplicated. A v. cardiaca was found in 25 cases (83.3%), when it was most frequently a tributary of the v. gastroepiploica sinistra and v. gastrica sinistra. In one case only it was an independent tributary of the v. portae. A v. pylorica was observed in 29 cases (96.7%), usually (in 17 cases--56.7%) as a tributary of the v. gastroepiploica dextra; in three cases it was an independent tributary of the v. portae (10.0%). A v. pancreaticoduodenalis cranialis was formed in 28 cases (93.3%). In 12 cases (40.0%), together with the v. gastroepiploica dextra, it was a tributary of the v. gastroduodenalis and in eight cases (26.7%) it was an independent tributary of the v. portae. In two cases (6.7%) the two vv. pancreaticoduodenales united to form v. pancreaticoduodenalis communis. In three cases (10.0%) this vein was duplicated and in one case it was triplicated. A v. gastroepiploica dextra was found in 26 cases (86.7%) and a v. gastroepiploica sinistra in 22 (73.3%). Both veins occurred simultaneously in 19 cases (63.3%). In no case, however, was there a continuous venous arc along the curvatura major ventriculi. A v. lienalis was present in 28 cases (93.3%). It was absent in two cases (6.7%), in which it was replaced by inter-organ anastomoses with the stomach and pancreas. In 19 cases (63.3%), the v. gastroepiploica sinistra and v. gastrica sinistra were both its main tributaries and in five cases (16.7%) its main tributary was the v. gastrica sinistra. In one case the v. lienalis was duplicated. Inter-organ anastomoses were formed in all 30 cases (100%). They occurred between the spleen and the stomach in 27 cases (90%) and between the spleen and the pancreas in 28 cases (93.3%).(ABSTRACT TRUNCATED AT 400 WORDS)

The v. portae of the domestic cat and variability of its tributaries.

In the domestic cat the v. portae originates as a thick venous trunk below the liver through confluence of the v. gastrica sinistra, v. lienalis and v. mesenterica cranialis. It was formed in this way in 19 cases, i.e. in 63.3%. Among the aberrations found in the other cases, the most frequent was a common trunk for the v. gastrica sinistra and v. lienalis (6.7%). In 26 cases (86.6%), the v. gastrica sinistra was an independent tributary of the v. portae. A single v. lienalis was found in 27 cases (90.0%). Inter-organ anastomoses were found in the region of the v. lienalis. In 29 cases (96.7%) they connected the cranial part of the spleen with the fundus ventriculi. Inter-organ venous anastomoses between the caudal part of the spleen and the pancreas were found in four cases (13.4%). These anastomoses came from within the spleen and joined the veins of the stomach or the pancreas. In 14 cases (46.6%) the v. mesenterica cranialis originated as the v. colica dextra or v. caecalis. In nine cases (30.0%), in the concavity of the small intestine we found two trunks forming the v. mesenterica cranialis-one from the caecum and the other from the ileum and jejunum. Lastly, in five cases (16.7%) the v. mesenterica cranialis started only from the ileum and jejunum. The most frequent first tributary-in 19 cases (63.3%)-was a venous trunk of varying length formed by union of the v. mesenterica caudalis and the v. colica media, which started in 11 cases (36.7%) as the v. colica dextra.(ABSTRACT TRUNCATED AT 250 WORDS)

Origin of the v. portae and variability of its tributaries in laboratory animals. II. The guinea pig (Cavia aperea f. porcellus).

The authors investigated the origin of the v. portae and variability of its main tributaries in 30 adult guinea pigs (Cavia aperea f. porcellus). The venous bed was visualized by means of blue-dyed latex. The v. portae was formed the most frequently - in 17 cases (56.7%) - by the confluence of three veins - the v. mesenterica cranialis, the v. lienalis and the v. gastroepiploica dextra; less often it was formed from four or five tributaries and in one case only it was formed by union of the v. mesenterica cranialis and the v. lienalis. The v. gastrica sinistra was a tributary of the v. lienalis in 24 cases (80.0%). It arose on the ventral and the dorsal surface of the stomach, in the region adjacent to the curvatura minor ventriculi. In 21 cases (70.0%) it was joined by an independent v. cardiaca. The v. lienalis originated in the hilus lienis, usually as a result of the union of two venous trunks. Inter-organ anastomoses were found in 26 cases (86.7%); in 10 cases (33.3%) they occurred simultaneously between the spleen and the stomach and between the spleen and the pancreas, while in 16 cases (53.3%) they connected the superior pole of the spleen with the stomach. An independent v. gastroepiploica dextra was present in 19 cases (63.3%) as a tributary of the v. portae. In 22 cases it was joined by the v. pylorica. A v. pancreaticoduodenalis cranialis was present in 27 cases (90.0%). In 18 cases (60.0%) it united with the v. gastroepiploica dextra to form a common trunk, the v. gastroduodenalis, which joined the v. portae; in two cases (6.7%) it was an independent tributary of the v. portae. In six cases it was connected with the v. lienalis and in three cases (10.0%) it was replaced by a few vv. pancreaticae emptying into the v. lienalis. A typical v. pancreaticoduodenalis caudalis, as a tributary of the a. mesenterica cranialis, was found in 19 cases (63.3%). In two cases, together with the v. pancreaticoduodenalis cranialis, it formed a single trunk (the v. pancreaticoduodenalis communis). A comparison of the v. portae and its tributaries in the guinea pig and the cat has so far not brought to light any significant morphological differences relative to their different zoological classification and their different modes of life.

Origin of the v. portae and variability of its tributaries in laboratory animals. III. The laboratory rat (Rattus norvegicus var. alba).

The authors studied the origin of the v. portae and the variability of its tributaries in 30 adult laboratory rats (Rattus norvegicus v. alba) after injecting blue-dyed latex into the venous bed. In 21 cases (70.0%) the v. portae was formed from three tributaries. In 18 of these cases (60.0%) they were the v. mesenterica cranialis, v. lienalis and v. pancreaticoduodenalis cranialis. In eight cases the v. portae was formed from four or five tributaries and in only one case was it formed from two--the v. mesenterica cranialis and v. lienalis. In 21 cases (70.0%) the v. gastrica sinistra was a tributary of the v. lienalis. It collected blood from the anterior and posterior surface of the stomach and sometimes originated as far away as the curvatura major ventriculi. A v. cardiaca was present in all 30 cases (100%). As a rule (in 28 cases, i.e. 93.3%), it was a tributary of the v. gastrica sinistra. There was likewise a v. pylorica in every case; most frequently this united with the v. pancreaticoduodenalis cranialis, but was also connected with other veins in the vicinity. A v. pancreaticoduodenalis cranialis was always present. In 22 cases (73.3%) it was an independent tributary of the v. portae. In 11 cases (36.7%), there were no vv. gastroepiploicae or equivalent vessels and blood from the stomach was drained mainly by the v. gastrica sinistra. A v. gastroepiploica dextra was present in 11 cases (36.7%), mostly as a tributary of the v. lienalis; in two cases (6.7%) there was a v. gastroepiploica sinistra and in six cases (20%) the place of these veins was taken by vv. gastricae as tributaries of the v. lienalis. In 21 cases (70.0%) the v. lienalis was joined by the v. gastrica sinistra. In 22 cases (73.3%) inter-organ anastomoses between the spleen, stomach and pancreas were found. A v. pancreaticoduodenalis caudalis was always present and in 20 cases (66.7%) it was an independent tributary of the v. mesenterica cranialis. A comparison of the origin of the v. portae and the organization and variability of its tributaries in the rat, cat and guinea pig shows that, in agreement with their position in the zoological system and their mode of life, there was greater similarity between the rat and the guinea pig as regards practically all the veins examined.

Origin of the v. portae and variability of its tributaries in laboratory animals. IV. The domestic rabbit (Oryctolagus cuniculus f. domestica, breed large chinchilla).

The authors studied the origin and variability of the tributaries of the v. portae in 30 domestic rabbits (Oryctolagus cuniculus f. domestica, breed Large Chinchilla) following the injection of blue-dyed latex into their portal bed. In 16 cases (53.3%), the v. portae was formed from four tributaries and in nine cases (30.0%) from three. The only constant contributory veins were the v. mesenterica cranialis and v. lienalis; the other tributaries (the v. gastroduodenalis. v. pancreaticoduodenalis cranialis and v. gastroepiploica dextra, etc) were variable. In 26 cases (86.7%), the v. gastrica sinistra joined the v. lienalis. In six cases (20.0%) it was an independent tributary of the v. portae and in six cases (20.0%) it was doubled. A v. cardiaca was found in all 30 rabbits (100%). In 23 (76.7%) it was a tributary of the v. gastrica sinistra and in seven (23.3%) it was an independent tributary of the v. portae. A v. pylorica was also present in all 30 cases (100%). In 16 (53.3%) it united with the v. gastroepiploica dextra, in eight (26.7%) it joined the v. gastroduodenalis and in four (13.3%) it was a tributary of the v. pancreaticoduodenalis cranialis. A v. pancreaticoduodenalis cranialis was found in 29 cases (96.7%). In 17 cases (56.7%) it was one of the initial tributaries of the v. gastroduodenalis and in eight (26.7%) it participated in formation of the v. portae as an independent trunk. In two cases (6.7%) it was doubled, the more cranial vein being a tributary of the v. portae.(ABSTRACT TRUNCATED AT 250 WORDS)