Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enhanced contractile responsiveness to the calcium channel agonist Bay K 8644 has been documented in large conduit arteries and small muscular arteries from hypertensive rats. The present study examined the effects of Bay K 8644 on the intracellular calcium concentration ([Ca2+]i) in microvessels from stroke-prone spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Using microspectrofluorometry of fura-2, [Ca2+]i was measured in smooth muscle cells localized on arteriolar fragments (15-35 microns external diameter) isolated after collagenase digestion of the pancreas. Resting [Ca2+]i in hypertensive arterioles (94 +/- 6 nM, n = 29) did not differ from that in normotensive vessels (81 +/- 4 nM, n = 40). KCl (50 mM), applied alone and in the presence of Bay K 8644 (30 nM), stimulated increases in [Ca2+]i that were reversed in calcium-free solution and with nifedipine (10 microM), consistent with activation of potential-operated calcium channels. Potassium-induced calcium transients were consistently potentiated by Bay K 8644. The change in [Ca2+]i evoked by KCl alone or in combination with Bay K 8644 did not differ between arterioles from hypertensive and normotensive rats. In 24% of the vessels from hypertensive rats and in 29% of those from normotensive rats, Bay K 8644 evoked an increase in [Ca2+]i that did not differ significantly between the two strains. The findings indicate that, in contrast to observations made in larger arteries, there is no evidence of a functional abnormality in potential-operated calcium channels in very small arterioles from genetically hypertensive rats.
 ...
PMID:Calcium channel activation in arterioles from genetically hypertensive rats. 138 37

Intracranial bleeding is an important cause of brain masses and edema. To study the pathophysiology of intracerebral hemorrhage, we produced experimental hemorrhages in 53 rats and characterized the lesion by histology, brain water content, and behavior. Adult rats had 2 microliters saline containing 0.5 unit bacterial collagenase infused into the left caudate nucleus. Histologically, erythrocytes were seen around blood vessels at the needle puncture site within the first hour. By 4 hours there were hematomas, the size of which depended on the amount of collagenase injected. Necrotic masses containing fluid, blood cells, and fibrin were seen at 24 hours. Lipid-filled macrophages were observed at 7 days and cysts at 3 weeks. Water content was significantly increased 4, 24, and 48 hours after infusion at the needle puncture site and for 24 hours in posterior brain sections. Behavioral abnormalities were present for 48 hours, with recovery of function occurring during the first week. Brain tissue contains Type IV collagen in the basal lamina. Collagenase, which occurs in an inactive form in cells, is released and activated during injury, leading to disruption of the extracellular matrix. Collagenase-induced intracerebral hemorrhage is a reproducible animal model for the study of the effects of the hematoma and brain edema.
Stroke 1990 May
PMID:Collagenase-induced intracerebral hemorrhage in rats. 216 Jan 42

Viable Hepatocytes were isolated from adult canine liver by in situ collagenase perfusion, and cultured on collagen coated borosilicate glass plates (100 X 200mm) at confluent cell density. The medium of hepatocytes in the primary culture was L-15 supplemented with aprotinin 5000U/L, proline 30mg/L, insulin 10(-8)M, dexamethasone 10(-8)M, glucagon 10(-8)M, and h-EGF 10ng/ml. Long-stroke type bioartificial liver module consisted of 200 glass plates with hepatocytes. It contained 6 billion primary cultured cells in total, that is almost equivalent to 30% of the normal canine liver. All hepatocytes in the module were quite viable during 2 weeks in the perfusion culture, and maintained various liver functions at a high level. Gluconeogenesis was 368.0 +/- 15.4mg/module/hr, albumin synthesis was 19.1 +/- 2.5mg/module/day, ureogenesis was 3.7 +/- 0.1mg/module/hr, and ammonia metabolism was 8.4mg/module/hr. Moreover, those functions were maintained at least 2 weeks in the canine plasma as well as in the culture medium with hormones. This hybrid bioartificial liver may exert various liver functions like a liver in situ.
 ...
PMID:[Hybrid bioartificial liver using canine hepatocytes in primary culture]. 276 24

Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.
 ...
PMID:Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats. 1040 16

Because free radical mechanisms may contribute to brain injury in hemorrhagic stroke, the effect of the free radical trapping agent disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059) was investigated on outcome following intracerebral hemorrhage (ICH) in rat. ICH was induced in 20 adult rats by infusion of collagenase into the caudate-putamen. Thirty minutes later rats were treated with NXY-059 (50 mg/kg subcutaneous plus 8.8 mg/kg/h for 3 days subcutaneous delivered via implanted osmotic pumps) or saline (equivalent volumes). Magnetic resonance imaging 24 h after ICH confirmed that the hemorrhage was uniform in the two groups, and subsequent imaging at 7 and 42 days post-ICH showed that the hematoma resolved similarly in the two groups. Behavioral testing on days 1, 3, 7, 14, and 21 after ICH showed that rats treated with NXY-059 had significantly decreased neurological impairment at all times. Deficits in skilled forelimb use 4-5 weeks post-ICH, and in striatal function 6 weeks post-ICH, were not reduced by treatment with NXY-059. Treatment with NXY-059 significantly reduced the neutrophil infiltrate observed 48 h post-hemorrhage in the vicinity of the hematoma, and the number of TUNEL-positive cells 48 h post-hemorrhage at the hematoma margin. However, by 6 weeks there were no differences in neuronal densities in treated and control rats.
 ...
PMID:Efficacy of disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059), a free radical trapping agent, in a rat model of hemorrhagic stroke. 1116 36

[2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate (YM872 or zonampanel), an AMPA receptor antagonist, is in clinical development for acute ischemic cerebral infarction. Stroke patients are prone to have subsequent intracerebral hemorrhages. In order to predict potential adverse effects, YM872 was tested in a rat model with collagenase-induced intracerebral hemorrhage. The morphologically determined hematoma volumes after 24 h were compared between animal groups intravenously infused with 3600 U/kg/h heparin for 30 min, or with 20 or 40 mg/kg/h of YM872, or placebo for 4 h. Heparin enlarged hematoma volume, but neither dose of YM872 affected hematoma size. In a separate study, neurological deficits were scored at various days after intracerebral hemorrhage induction in animals with intravenous infusion for 24 h of 10 or 20 mg/kg/h YM872, or saline. The YM872 groups scored significantly better than the saline group at 14 days. These data suggest that YM872 does not exacerbate intracerebral hemorrhage and might accelerate recovery.
 ...
PMID:Effect of AMPA receptor antagonist YM872 on cerebral hematoma size and neurological recovery in the intracerebral hemorrhage rat model. 1270 61

The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.
 ...
PMID:Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model. 1271 30

Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, modulates cell death by interrupting classic pathways of apoptosis. Intracerebral hemorrhage (ICH) is a devastating acute neurological disorder, without effective treatment, in which a significant loss of neuronal cells is thought to occur by apoptosis. In this study, we evaluated whether TUDCA can reduce brain injury and improve neurological function after ICH in rats. Administration of TUDCA before or up to 6 h after stereotaxic collagenase injection into the striatum reduced lesion volumes at 2 days by as much as 50%. Apoptosis was approximately 50% decreased in the area immediately surrounding the hematoma and was associated with a similar inhibition of caspase activity. These changes were also associated with improved neurobehavioral deficits as assessed by rotational asymmetry, limb placement, and stepping ability. Furthermore, TUDCA treatment modulated expression of certain Bcl-2 family members, as well as NF-kappaB activity. In addition to its protective action at the mitochondrial membrane, TUDCA also activated the Akt-1protein kinase Balpha survival pathway and induced Bad phosphorylation at Ser-136. In conclusion, reduction of brain injury underlies the wide-range neuroprotective effects of TUDCA after ICH. Thus, given its clinical safety, TUDCA may provide a potentially useful treatment in patients with hemorrhagic stroke and perhaps other acute brain injuries associated with cell death by apoptosis.
 ...
PMID:Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats. 1272 62

Intracerebral hemorrhage (ICH) causes morbidity and mortality and commonly follows the reperfusion after an ischemic event. Tissue plasminogen activator (tPA), a fibrinolytic serine protease, is routinely given for the treatment of stroke. However, tPA also can promote neuronal death, suggesting that caution should be exercised when using it. Furthermore, tPA upon brain injury mediates microglial activation and modulates neuronal survival. To investigate the role of tPA and microglia during brain hemorrhage, we induced experimentally ICH by intracerebral injection of collagenase. Seven days after the introduction of ICH, it persisted in tPA-deficient (tPA(-/-)) mice but is drastically reduced in size in wild-type mice. Three weeks after ICH, there are still red blood cells in tPA(-/-) but not in wild-type animals. Activated microglia persist around the injury site. When microglial activation is inhibited by tuftsin fragment 1-3 macrophage/microglial inhibitory factor (MIF), the stroke injury volume is significantly reduced, and the neurobehavioral deficits exhibited by the mice are improved. Our results suggest that endogenous tPA assists in the clearance of intracerebral hemorrhage, presumably by affecting microglial activation, and MIF could be a valuable neuroprotective agent for the treatment of ICH.
 ...
PMID:Protective role of tuftsin fragment 1-3 in an animal model of intracerebral hemorrhage. 1459 55

Intracerebral hemorrhage is one of the most devastating types of stroke. This disease is known to cause severe neurological damage and also has a very high mortality rate. In this study, the effect of treadmill exercise on intrastriatal hemorrhage-induced neuronal cell death was investigated. Intrastriatal hemorrhage was caused by injection of collagenase into the striatum using a stereotaxic instrument. Animals of the exercise group were made to run on a treadmill for 30 min once a day during 10 consecutive days. In the present results, treadmill exercise was shown to suppress the increase in the size of hemorrhage-induced lesions and the increase in caspase-3 expression in the striatum. Based on these results, it is possible that treadmill exercise aids in the recovery from central nervous system sequelae following intracerebral hemorrhage.
 ...
PMID:Treadmill exercise decreases intrastriatal hemorrhage-induced neuronal cell death via suppression on caspase-3 expression in rats. 1461 43


1 2 3 4 5 6 7 8 9 10 Next >>