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Sample records for rat embolic stroke

  1. Characterization of the pattern of ischemic stroke induced by artificial particle embolization in the rat brain.

    PubMed

    Tsai, Ming-Jun; Tsai, Yi-Hung; Kuo, Yu-Min

    2011-09-01

    Embolism is responsible for half of cerebral infarctions, yet few animal models were developed due to the unpredictability of the embolus-induced infarcts. We manufactured artificial embolic particles by blending chitin and poly(D,L-Lactide-co-glycolide) (chitin/PLGA) for their good biocompatibility and rapid hydration expansion property. We subdivided the chitin/PLGA microparticles into 10 size groups (from 38-45 μm to 255-350 μm) and injected them through the external carotid artery toward the bifurcation of the common carotid artery in the rat. Reduced blood flow of the ipsilateral hemisphere was evident immediately after the injection of particles. The spherical appearance of the particle was critical in occluding the cerebral vessels. Particle(212-250 μm) produced the greatest diffuse infarction in the ipsilateral hemisphere, including the cortex, hippocampus, basal ganglion, thalamus, midbrain and cerebellum. Particle(75-90 μm) induced single or sparse isolated infarcts mainly located in the subcortical region, resembling lacunar stroke observed in humans. Particle(38-45 μm) frequently crossed to the contralateral hemisphere and induced diffuse infarctions in both hemispheres. The cortex infarct volumes were positively correlated to neurologic score and seizure incidence. In conclusion, we have established embolic stroke animal models, including a novel model that mainly expresses lacunar infarction, by intravenous injection of chitin/PLGA microparticles. PMID:21665272

  2. Effect of recombinant plasminogen activator timing on thrombolysis in a novel rat embolic stroke model.

    PubMed

    Ma, Yinzhong; Li, Li; Niu, Ziran; Song, Junke; Lin, Yihuang; Zhang, Huifang; Du, Guanhua

    2016-05-01

    The treatment of acute ischemic stroke (AIS) using thrombolysis with recombinant tissue-plasminogen activator (rtPA, alteplase) is limited by its narrow time window and the risk of hemorrhage. Recombinant plasminogen activator (rPA, reteplase) has been used clinically on coronary artery thrombosis and acute myocardial infarction. It is necessary to induce strokes experimentally as a means of validating the rPA timing on patients with AIS. However, current embolic models cannot mimic clinical situations well due to the embolus's composition of dried blood clots or artificial materials. In this paper, we used two novel rat thromboembolic models to determine the dosage-effect relationship and therapeutic time window of r-PA. Male rats were administered rPA or rtPA intravenously at 2-12h postischemia. Cerebral blood flow, behavioral outcomes and infarct volume within the same animal group were determined. Our results demonstrated that rPA (0.2 and 0.4mg/kg) or rtPA (0.2mg/kg) restored focal perfusion, reduced cerebral infarction, and improved behavioral outcomes at 2-4h postischemia. rPA but not rtPA significantly restored focal perfusion at 6h postischemia. However, delayed rPA-treatment neither decreased infarct volume nor improved the neurological disorder. Cerebral hemorrhage occurred at 6h postischemia detected by Evan's blue leakage and tissue hemoglobin content. Collectively, Thrombolysis with rPA may be beneficial in revascularization at an acceptable dosage of 0.2-0.4mg/kg within 6h after the cerebral infarct onset. PMID:27038532

  3. Efficacy of recombinant annexin 2 for fibrinolytic therapy in a rat embolic stroke model: A magnetic resonance imaging study

    PubMed Central

    Tanaka, Yoji; Ishii, Hideto; Hiraoka, Megumi; Miyasaka, Naoyuki; Kuroiwa, Toshihiko; Hajjar, Katherine A.; Nagaoka, Tsukasa; Duong, Timothy Q.; Ohno, Kikuo; Yoshida, Masayuki

    2010-01-01

    Efficacy of recombinant annexin 2 (rAN II) in a rat model of embolic stroke was examined using a magnetic resonance imaging (MRI) and histology. The right middle cerebral artery of male Wistar rats was occluded by autologous clots under anesthesia. Four doses of rAN II (0.125, 0.25, 0.5 and 1.0 mg/kg, n = 10 for each group) or saline (1 ml/kg, n = 10) were administrated intravenously within 5 min before clot infusion. Serial changes in apparent diffusion coefficient (ADC) and relative blood flow (CBF) were measured with the use of MRI in half of the animals in each group. The remaining half of the animals in each group was evaluated for hemorrhage and final infarct size by histology at 48 h after embolization. At 3 h after embolization, lesion volumes with ADC were abnormality and CBF in the peripheral lesion was improved in groups treated with 0.25, 0.5 and 1.0 mg/kg, but not 0.125 mg/kg, of rAN II in comparison with the saline-treated group (P < 0.05). Histological analyses were consistent with MRI findings. More importantly, no hemorrhagic transformation was documented in rats treated with 0.125 and 0.25 mg/kg of rAN II, whereas it was observed at higher doses. We concluded that rAN II at 0.25 mg/kg significantly reduced infarct size and improved CBF without hemorrhagic complications. rAN II is a novel compound that has the potential to be a promising fibrinolytic agent to treat embolic stroke. PMID:17651708

  4. Visualization of Clot Lysis in a Rat Embolic Stroke Model: Application to Comparative Lytic Efficacy

    PubMed Central

    Walvick, Ronn P.; Bråtane, Bernt T.; Henninger, Nils; Sicard, Kenneth M.; Bouley, James; Yu, Zhanyang; Lo, Eng; Wang, Xiaoying; Fisher, Marc

    2011-01-01

    Background and Purpose The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model, and to compare tissue plasminogen activator (tPA) based clot lysis with and without recombinant Annexin-2 (rA2). Methods Experiment 1: In vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50μL in 250μL blood. Experiment 2: In vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot imaging were conducted prior to and during treatment with vehicle (n=6), tPA (n=8) or rA2+tPA (n=8) at multiple time-points. Brains were removed for ex vivo clot localization. Results Clots created with 25μL Magnevist© were the most stable and provided the highest contrast-to-noise ratio. In the vehicle group, clot length as assessed by T1-weighted imaging correlated with histology (r=0.93). Clot length and CBF-derived ischemic lesion volume were significantly smaller than vehicle at 15 minutes post-treatment initiation in the rA2+tPA group, while in the tPA group no significant reduction from vehicle was observed until 30 minutes post-treatment initiation. The rA2+tPA group had a significantly shorter clot length than the tPA group at 60 and 90 minutes post-treatment initiation, and significantly smaller CBF deficit than the tPA group at 90 minutes post-treatment initiation. Conclusions We introduce a novel MRI based clot imaging method for in vivo monitoring of clot lysis. Lytic efficacy of tPA was enhanced by rA2. PMID:21372305

  5. A novel quantification of blood-brain barrier damage and histochemical typing after embolic stroke in rats.

    PubMed

    Michalski, Dominik; Grosche, Jens; Pelz, Johann; Schneider, Dietmar; Weise, Christopher; Bauer, Ute; Kacza, Johannes; Gärtner, Ulrich; Hobohm, Carsten; Härtig, Wolfgang

    2010-11-01

    Treatment strategies in acute ischemic stroke are still limited. Considering numerous translation failures, research is tending to a preferred use of human-like animal models, and a more-complex perspective of tissue salvaging involving endothelial, glial and neuronal components according to the neurovascular unit (NVU) concept. During ischemia, blood-brain barrier (BBB) alterations lead to brain edema and hemorrhagic transformation affecting NVU components. The present study aims on a novel quantification method of BBB damage and affected tissue following experimental cerebral ischemia, closely to the human condition. Wistar rats underwent embolic middle cerebral artery occlusion, followed by an intravenous application of fluorescein isothiocyanate (FITC)-tagged albumin (≈70kDa) and/or biotinylated rat IgG (≈150kDa) as BBB permeability markers. Both fluorescent agents revealed similar leakage and allow quantification of BBB permeability by fluorescence microscopy, and after immunohistochemical conversion into a permanent diaminobenzidine label at light-microscopical level. The following markers were identified for sufficient detection of NVU components: Rat endothelial cell antigen-1 (RECA) and laminin for vessels, Lycopersicon esculentum and Griffonia simplicifolia agglutinin for vessels and microglial subpopulations, ionized calcium binding adaptor molecule 1 (Iba1), CD68 and CD11b for macrophages, activated microglia, monocytes and neutrophils, S100β for astroglia, as well as NeuN and HuC/D for neurons. This is the first report confirming the usefulness of simultaneously applied FITC-albumin and biotinylated rat IgG as BBB permeability markers in experimental stroke, and, specifying antibodies and lectins for multiple fluorescence labeling of NVU components. Newly elaborated protocols might facilitate a more-complex outcome measurement in drug development for cerebral ischemia. PMID:20732314

  6. Angiogenesis and Improved Cerebral Blood Flow in the Ischemic Boundary Area Detected by MRI after Administration of Sildenafil to Rats with Embolic Stroke

    PubMed Central

    Li, Lian; Jiang, Quan; Zhang, Li; Ding, Guangliang; Zhang, Zheng Gang; Li, Qingjiang; Ewing, James R.; Lu, Mei; Panda, Swayamprava; Ledbetter, Karyn A.; Whitton, Polly A.; Chopp, Michael

    2007-01-01

    To dynamically investigate the long-term response of an ischemic lesion in rat brain to the administration of sildenafil, male Wistar rats subjected to embolic stroke were treated with sildenafil (n=11) or saline (n=10) at a dose of 10mg/Kg administered subcutaneously 24-hours after stroke and daily for an additional 6-days. Magnetic resonance images were acquired and functional performance was measured in all animals at 1-day, 2-days and weekly for 6-weeks post-stroke. All rats were sacrificed 6-weeks after stroke and endothelial barrier antigen immunostaining was employed for morphological analysis and quantification of cerebral vessels. Map-ISODATA was computed from T1, T2 and T1sat maps. ISODATA derived tissue signatures characterize the degree of ischemic injury. Based on the map-ISODATA calculated at 6-weeks, the ischemic lesion for each animal was divided into two specific regions, the ischemic boundary and ischemic core. The temporal profiles of cerebral blood flow (CBF) and tissue signature were retrospectively tracked in these two regions and were compared with histological evaluation and functional outcome. After 1-week of sildenafil treatment, the ischemic lesion exhibited two significantly different regions, with higher CBF level and correspondingly, lower tissue signature value in the boundary region than in the core region. Sildenafil treatment did not significantly reduce the lesion size, but did enhance angiogenesis. Functional performance was significantly increased after sildenafil treatment compared with the control group. Administration of sildenafil to rats with embolic stroke enhances angiogenesis and selectively increases the CBF level in the ischemic boundary, and improves neurological functional recovery compared to saline-treated rats. PMID:17188664

  7. Radiological Portrait of Embolic Strokes.

    PubMed

    Sachdeva, Gautam; Saeed, Ali; Jani, Vishal; Razak, Anmar

    2016-05-01

    Stroke is the leading cause of adult disability and the fifth leading cause of death in the United States. In 2010, the cost of stroke to the health care system in the United States was estimated to be $71.55 billion, and it is projected to double over the next 20 years. Cardioembolism is a leading pathophysiologic cause of stroke. Along with a careful review of the presenting history and clinical symptomatology, early radiographic studies including computed tomography (CT) and MRI, may demonstrate certain characteristics that may be suggestive of a cardioembolic origin to a stroke of concern. PMID:27150175

  8. Focal embolic cerebral ischemia in the rat

    PubMed Central

    Zhang, Li; Zhang, Rui Lan; Jiang, Quan; Ding, Guangliang; Chopp, Michael; Zhang, Zheng Gang

    2015-01-01

    Animal models of focal cerebral ischemia are well accepted for investigating the pathogenesis and potential treatment strategies for human stroke. Occlusion of the middle cerebral artery (MCA) with an endovascular filament is a widely used model to induce focal cerebral ischemia. However, this model is not amenable to thrombolytic therapies. As thrombolysis with recombinant tissue plasminogen activator (rtPA) is a standard of care within 4.5 hours of human stroke onset, suitable animal models that mimic cellular and molecular mechanisms of thrombosis and thrombolysis of stroke are required. By occluding the MCA with a fibrin-rich allogeneic clot, we have developed an embolic model of MCA occlusion in the rat, which recapitulates the key components of thrombotic development and of thrombolytic therapy of rtPA observed from human ischemic stroke. The surgical procedures of our model can be typically completed within approximately 30 min and are highly adaptable to other strains of rats as well as mice for both genders. Thus, this model provides a powerful tool for translational stroke research. PMID:25741989

  9. Patent Foramen Ovale: Is Stroke Due to Paradoxical Embolism?

    NASA Technical Reports Server (NTRS)

    Ranoux, D.; Cohen, A.; Cabanes, L.; Amarenco, P.; Bousser, M. G.; Mas, J. L.

    1993-01-01

    Background and Purpose: A patent foramen ovale has been reported to be significantly more frequent in young stroke patients than in matched control subjects, and paradoxical embolism has been suggested as the main mechanism of stroke in-this situation. The present study was designed to test this hypothesis. Methods: Sixty-eight consecutive patients under 55 years of age presenting with an ischemic stroke had an extensive workup, including transesophageal echocardiography with contrast. We compared the prevalence of criteria for the diagnosis of paradoxical embolism in patients with and without a patent foramen ovale. Results: A patent foramen ovale was found in 32 patients (47%). A Valsalva-provoking activity was present at stroke onset in six patients with a patent foramen ovale and in eight patients with no patent foramen ovale (X(sup 2)=0.1, nonsignificant). Clinical/radiological features suggestive of an embolic mechanism were not more frequent in patients with a patent foramen ovale. Clinical evidence of deep vein thrombosis was present in one patient with a patent foramen ovale and in none of the others. No occult venous thrombosis was found in a subgroup of patients with a patent foramen ovale and no definite cause for stroke who underwent venography (n=13). Conclusions. Our results do not support the hypothesis that paradoxical embolism is the primary mechanism of stroke in patients with a patent foramen ovale. (Stroke 1993;24:31-34) KEY WORDS e cerebral ischemia e embolism foramen ovale, patent

  10. Rate and extent of leakage of a magnetic resonance contrast agent tend to be lower under isoflurane anesthesia in comparison to halothane in a rat model of embolic stroke.

    PubMed

    Bezerra, Francisco J; Brown, Morris; Alarcon, William; Karki, Kishor; Knight, Robert A; Keenan, Kelly A; Nagaraja, Tavarekere N

    2014-09-01

    Cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability by arterial spin labeling (ASL)- and dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI), respectively were repeatedly measured under either halothane (N  =  5) or isoflurane (N  =  5) anesthesia in a rat stroke model of embolic occlusion of middle cerebral artery (MCA). Cerebral blood flow measurements were made after MCA embolization, following intravenous recombinant tissue plasminogen activator (rtPA) treatment at 3 hours post-ictus and again at 48 hours. Blood-brain barrier opening was examined after rtPA infusion and again at 48 hours. Data were analyzed using paired t-tests and significance considered at P < 0·05. The extent and magnitude of CBF reduction due to stroke did not differ between the two groups. Blood-to-brain forward rate constant, K(trans), a measure of BBB permeability, for an MRI contrast agent gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), was elevated in the ipsilateral hemisphere in both cohorts. However, isoflurane-anesthetized rats exhibited a trend of lower K(trans) values at 48 hours (P  =  0·06) indicating reduced BBB damage in the ipsilateral hemisphere. The area of BBB opening followed a similar trend with the isoflurane-anesthetized group exhibiting a smaller area of BBB damage acutely and at 48 hours compared to the halothane-anesthetized group. PMID:24601723

  11. Embolic Strokes of Unknown Source and Cryptogenic Stroke: Implications in Clinical Practice

    PubMed Central

    Nouh, Amre; Hussain, Mohammed; Mehta, Tapan; Yaghi, Shadi

    2016-01-01

    Up to a third of strokes are rendered cryptogenic or of undetermined etiology. This number is specifically higher in younger patients. At times, inadequate diagnostic workups, multiple causes, or an under-recognized etiology contributes to this statistic. Embolic stroke of undetermined source, a new clinical entity particularly refers to patients with embolic stroke for whom the etiology of embolism remains unidentified despite through investigations ruling out established cardiac and vascular sources. In this article, we review current classification and discuss important clinical considerations in these patients; highlighting cardiac arrhythmias and structural abnormalities, patent foramen ovale, paradoxical sources, and potentially under-recognized, vascular, inflammatory, autoimmune, and hematologic sources in relation to clinical practice. PMID:27047443

  12. Early embolic events complicating intravenous thrombolysis for acute ischemic stroke.

    PubMed

    Chou, Ping Song; Lin, Chien Hung; Chao, Hai Lun; Chao, A Ching

    2012-11-01

    Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke. However, secondary embolism after IV rt-PA for acute ischemic stroke is recognized as an uncommon complication, and the pathophysiology is unclear. We describe a 72-year-old man with acute infarction in the territory of left anterior cerebral artery who developed new infarction in the territory of right middle cerebral artery and acute peripheral arterial occlusion after IV rt-PA therapy. It suggested a central embolic source. Because the patient has paroxysmal atrial fibrillation (Af), the possible embolic sources may come from fragmentation of pre-existing intra-atrial clot. Although Af and the presence of cardiac thrombus are not contraindication for IV rt-PA in acute ischemic stroke, our case and review suggested that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated. PMID:22205004

  13. Ischemic stroke related to an amniotic fluid embolism during labor.

    PubMed

    Woo, Yeon-Sun; Hong, Soon-Cheol; Park, Seong-Mi; Cho, Kyung-Hee

    2015-04-01

    We report a young woman who survived multiple cerebral infarctions related to an amniotic fluid embolism (AFE) during labor. To our knowledge, an embolic stroke due to the coexistence of an AFE and patent foramen ovale (PFO) has not been reported. We describe the patient's clinical and radiological features and discuss the stroke mechanism in relation to our AFE hypothesis. A 32-year-old woman presented to the emergency room after experiencing convulsions during labor (blood pressure, 64/28mmHg; oxygen saturation, 67%). She was in a stupor, and her response to painful stimuli on the right side was weaker than on the left side. Acute stroke was considered as a possible cause. Additionally, an AFE was suspected due to cardiopulmonary arrest during labor. Brain MRI revealed multiple territory embolic infarctions. The transcranial Doppler with bubble study demonstrated a right-to-left shunt during the Valsalva maneuver. A transesophageal echocardiogram revealed a PFO with a right-to-left shunt. The elevated intrathoracic pressure during labor may have caused blood to flow backward through the heart, shunting blood from the right side to the left through the PFO. In cases such as this, an amniotic fluid embolus may travel directly from the venous to the arterial circulation via the PFO, leading to multiple cerebral infarctions. PMID:25709056

  14. Neurological Assessment Scores in Rabbit Embolic Stroke Models

    PubMed Central

    Brown, Aliza; Woods, Sean; Skinner, Robert; Hatton, Jeff; Lowery, John; Roberson, Paula; Hennings, Leah; Culp, William C

    2013-01-01

    Background: Neurological outcomes and behavioral assessments are widely used in animal models of stroke, but assessments in rabbit models are not fully validated. The wryneck model of neurological assessment scores (NAS) was compared to percent infarct volume (%IV) values (infarct volume is a proven clinical indicator of stroke severity) and arterial occlusion localization in three rabbit angiographic stroke models. Hypothesis: NAS values will correlate with percent infarct volume values. Methods: Anesthetized New Zealand White rabbits (N=131, 4-5 kg) received internal carotid artery emboli by angiographic catheter introduced into the femoral artery and occlusions were characterized. Rabbits were evaluated at 24 hours post embolism using the NAS test of 0 (normal) to 10 (death). Deficit criteria included neck twist, righting reflex, extension reflex in hind paw and forepaw, and posture. Brain sections stained with triphenyltetrazolium chloride (TTC) were analyzed for %IV. Volume of the infarct was measured and calculated as a percent of the total brain volume. Results: The aggregate correlation for NAS values vs. %IV values was R=0.61, p<0.0001, a strong positive relationship, while correlations of the NAS components ranged from R=0.28-0.46. Occlusionsof the posterior cerebral artery vs. the middle cerebral artery alone produced significantly greater deficit scores at p<0.0001. Conclusions: These positive results validate the NAS system in the rabbit angiographic embolic stroke model. PMID:24265650

  15. The Influence of Acute Hyperglycemia in an Animal Model of Lacunar Stroke That Is Induced by Artificial Particle Embolization

    PubMed Central

    Tsai, Ming-Jun; Lin, Ming-Wei; Huang, Yaw-Bin; Kuo, Yu-Min; Tsai, Yi-Hung

    2016-01-01

    Animal and clinical studies have revealed that hyperglycemia during ischemic stroke increases the stroke's severity and the infarct size in clinical and animal studies. However, no conclusive evidence demonstrates that acute hyperglycemia worsens post-stroke outcomes and increases infarct size in lacunar stroke. In this study, we developed a rat model of lacunar stroke that was induced via the injection of artificial embolic particles during full consciousness. We then used this model to compare the acute influence of hyperglycemia in lacunar stroke and diffuse infarction, by evaluating neurologic behavior and the rate, size, and location of the infarction. The time course of the neurologic deficits was clearly recorded from immediately after induction to 24 h post-stroke in both types of stroke. We found that acute hyperglycemia aggravated the neurologic deficit in diffuse infarction at 24 h after stroke, and also aggravated the cerebral infarct. Furthermore, the infarct volumes of the basal ganglion, thalamus, hippocampus, and cerebellum but not the cortex were positively correlated with serum glucose levels. In contrast, acute hyperglycemia reduced the infarct volume and neurologic symptoms in lacunar stroke within 4 min after stroke induction, and this effect persisted for up to 24 h post-stroke. In conclusion, acute hyperglycemia aggravated the neurologic outcomes in diffuse infarction, although it significantly reduced the size of the cerebral infarct and improved the neurologic deficits in lacunar stroke. PMID:27226775

  16. Proinflammatory cytokines in the embolic model of cerebral ischemia in rat.

    PubMed

    Jafarinaveh, Hamid Reza; Allahtavakoli, Mohammad; Rezazadeh, Hossein; Kazemi Arababadi, Mohammad; Taghavi, Mohammad Mohsen; Shamsizadeh, Ali; Rahmani, Mohammad Reza

    2014-04-01

    Increased levels of proinflammatory cytokines have been recorded after the onset of transient or permanent brain ischemia and are usually associated with exacerbation of ischemic injury. Embolic stroke model is more relevant to the pathophysiological situation in such patients, because the majority of ischemic injuries in humans are induced by old thrombi that originate from the heart and carotid arteries. Therefore, the aim of the present study was to investigate changes of inflammatory cytokines after embolic stroke. Rats were subjected to embolic stroke, induced by a natural old clot which was injected in Middle Cerebral Artery (MCA), or sham stroke, which the same volume of saline was injected into the MCA. At 48 h after stroke induction, the levels of 5 cytokines (IL-1α and β, IL-6, IFN-γ and TNF-α) were determined in 500 µg of total protein using the Bio-Plex Rat Cytokine Array (BioRad), according to the manufacturer's instructions in ischemic and non-ischemic cortices. While stroke animals showed infarctions and neurological deficits, we did not observe any cerebral infarction and neurological deficits in sham-operated animals. The levels of IL-1α (p=0.000) and -β (p =0.004), IL-6 (p =0.008), TNF-α (p =0.000) and IFN-γ (p =0.044) were significantly increased compared to sham treated animals. The findings of the present study suggest that part of ischemic injury in the embolic stroke may be mediated through the increased levels of inflammatory cytokines. PMID:24338258

  17. Recurrent Embolic Strokes of Undetermined Source in a Patient with Extreme Lipoprotein(a) Levels

    PubMed Central

    Bulwa, Zachary; Kim, Audrey; Singh, Karandeep; Kantorovich, Alexander; Suhail, Faten

    2016-01-01

    Lipoprotein(a) is a plasma lipoprotein and known cardiovascular risk factor, most recently implicated in the development of high-risk carotid atherosclerotic plaques without significant carotid stenosis. We present a case of a young African-American female with recurrent embolic strokes of undetermined source. After our thorough investigation, we identified the link between a small, irregular plaque in the right internal carotid artery, and an extremely elevated plasma level of lipoprotein(a) as the source of her embolic strokes.

  18. Cardio-embolic stroke following remote blunt chest trauma.

    PubMed

    Arora, Sonali; Atreya, Auras R; Penumetsa, Srikanth C; Hiser, William L

    2013-03-01

    A cardio-embolic stroke as a sequela of remote blunt chest trauma is a rare clinical presentation. Blunt chest trauma can cause various acute cardiac complications like arrhythmias, cardiac contusion etc. However, delayed consequences such as left ventricular thrombus resulting in thromboembolic phenomena are reported infrequently. A 30-year-old healthy man presented to an outside facility with transient neurological deficits. An MRI brain showed lesions suggestive of embolic etiology. A trans-thoracic echocardiogram (TTE) showed a 1.5 × 1.5 cm mass present in the left ventricular (LV) apex. Patient was transferred to our institution for cardiac surgery evaluation. On detailed questioning, he reported an incident of blunt chest trauma during a martial arts exhibition fight that took place 2 years back. Given this history, a cardiac catheterization was done, which showed 30% stenosis in mid-left anterior descending artery (LAD) without any other significant obstructive lesion. A trans-esophageal echocardiogram (TEE) showed akinesis of the LV apex and confirmed TTE finding of a mass, consistent with an apical thrombus. Surgery was deferred and patient was started on anticoagulation. A cardiac MRI done 2 weeks later showed evidence of apical infarction in the LAD territory. LAD is the most commonly affected coronary vessel by blunt traumatic injuries, likely due to its vulnerable anatomical position on the anterior aspect of the heart. A variety of mechanisms including intimal tear, rupture and spasm have been implicated in the pathogenesis of myocardial infarction after blunt chest trauma. PMID:24023477

  19. Numerical investigation of fluid-particle interactions for embolic stroke

    NASA Astrophysics Data System (ADS)

    Mukherjee, Debanjan; Padilla, Jose; Shadden, Shawn C.

    2016-04-01

    Roughly one-third of all strokes are caused by an embolus traveling to a cerebral artery and blocking blood flow in the brain. The objective of this study is to gain a detailed understanding of the dynamics of embolic particles within arteries. Patient computed tomography image is used to construct a three-dimensional model of the carotid bifurcation. An idealized carotid bifurcation model of same vessel diameters was also constructed for comparison. Blood flow velocities and embolic particle trajectories are resolved using a coupled Euler-Lagrange approach. Blood is modeled as a Newtonian fluid, discretized using the finite volume method, with physiologically appropriate inflow and outflow boundary conditions. The embolus trajectory is modeled using Lagrangian particle equations accounting for embolus interaction with blood as well as vessel wall. Both one- and two-way fluid-particle coupling are considered, the latter being implemented using momentum sources augmented to the discretized flow equations. It was observed that for small-to-moderate particle sizes (relative to vessel diameters), the estimated particle distribution ratio—with and without the inclusion of two-way fluid-particle momentum exchange—were found to be similar. The maximum observed differences in distribution ratio with and without the coupling were found to be higher for the idealized bifurcation model. Additionally, the distribution was found to be reasonably matching the volumetric flow distribution for the idealized model, while a notable deviation from volumetric flow was observed in the anatomical model. It was also observed from an analysis of particle path lines that particle interaction with helical flow, characteristic of anatomical vasculature models, could play a prominent role in transport of embolic particle. The results indicate therefore that flow helicity could be an important hemodynamic indicator for analysis of embolus particle transport. Additionally, in the presence

  20. Deep Crater in Heavily Calcified Aortic Valve Leaflet: A "Smoking Gun" for Embolic Stroke.

    PubMed

    Xu, Sarah Chaoying; Canter, Lisa; Zeeshan, Ahmad; Elefteriades, John A

    2015-10-01

    The association of severe calcific aortic stenosis with clinically significant stroke has not been well established. This case vividly describes the relationship with clinical and pathological (gross and microscopic) findings in a 62-year-old man with a severely calcified bicuspid aortic valve. Eleven months prior to aortic valve surgery, the patient had stigmata of cerebral embolic events in the absence of any other embolic source. During the aortic valve replacement surgery for aortic stenosis, he was found to have a large atheroma on the aortic valve cusp with a crater containing friable debris in its center. These findings support the potential for embolic stroke in patients with severe calcific aortic stenosis. We recommend that the aortic valve be considered as an embolic source in patients with an otherwise cryptogenic cerebrovascular accident. PMID:27175368

  1. Ischemic stroke due to paradoxical embolism arising from a popliteal vein aneurysm.

    PubMed

    Auboire, Laurent; Palcau, Laura; Mackowiak, Elise; Viader, Fausto; Le Hello, Claire; Berger, Ludovic

    2014-04-01

    Popliteal vein aneurysm (PVA) is a very uncommon cause of stroke. We present the case of a 63-year-old, right-handed man who presented to the emergency department with transitory ischemic accident (left superior extremity regressive monoplegia). Complete etiologic work-up led to the discovery of both a patent foramen ovale associated with an septum interauricular aneurysm, and of a PVA without mural thrombus. The diagnosis of brain paradoxical embolism was retained. The unique potentially embolic cause was the presence of the PVA. We decided to treat the PVA surgically to avoid a further cerebral vascular episode. Although uncommon, venous etiology must be considered for stroke. PMID:24360944

  2. Acute ischemic non-embolic stroke and serum level of uric acid

    PubMed Central

    Sheykholeslami, Nazanin Zia; Gadari, Faranak; Ahmady, Jafar

    2012-01-01

    Background Impact of high level of uric acid on stroke is still controversial. We conducted this study to investigate the relationship between acute ischemic non-embolic stroke and serum levels of uric acid. Methods This was a case-control study on patients with acute ischemic non-embolic stroke in Rafsanjan, Iran. The control group consisted of normal persons who were similar to the case group in terms of age and gender. Serum level of uric acid in the first 24 hours of admission was measured with photometry method. Results In a total of 130 patients (59 mens), hyperuricemia was seen in 13.0% of subjects in the control group and 10.7% of subjects in the case group. Nine patients in case group and 7 patients in control group with hyperuricemia were women. No significant relationship was found between acute ischemic non-embolic stroke and serum level of uric acid. Conclusion There was no relationship between uric acid and acute ischemic non-embolic stroke. PMID:24250850

  3. A novel method to promote behavioral improvement and enhance mitochondrial function following an embolic stroke.

    PubMed

    Lapchak, Paul A; Boitano, Paul D

    2016-09-01

    Tissue plasminogen activator (tPA) is the only FDA-approved treatment for stroke; tPA increases cerebral reperfusion, blood flow and improved behavior. Novel transcranial laser therapy (TLT) also enhances cerebral blood flow and activates mitochondrial function. Using the rabbit small clot embolic stroke model (RSCEM), we studied the effects of continuous wave TLT (7.5mW/cm(2)) alone or in combination with standardized intravenous (IV) tPA (3.3mg/kg) applied 1h post-embolization on 3 endpoints: 1) behavioral function measured 2 days [effective stroke dose (P50 in mg) producing neurological deficits in 50% of embolized rabbits], 2) intracerebral hemorrhage (ICH) rate, and 3) cortical adenosine-5'-triphosphate (ATP) content was measured 6h following embolization. TLT and tPA significantly (p<0.05) increased P50 values by 95% and 56% (p<0.05), respectively over control. TLT-tPA increased P50 by 136% over control (p<0.05). Embolization reduced cortical ATP content by 39%; decreases that were attenuated by either TLT or tPA treatment (p<0.05). TLT-tPA further enhanced cortical ATP levels 22% above that measured in naïve control. TLT and tPA both effectively and safely, without affecting ICH rate, improved behavioral outcome in embolized rabbits; and there was a trend (p>0.05) for the TLT-tPA combination to further increase P50. TLT and tPA both attenuated stroke-induced ATP deficits, and the combination of tPA and TLT produced an additive effect on ATP levels. This study demonstrates that the combination of TLT-tPA enhances ATP production, and suggests that tPA-induced reperfusion in combination with TLT neuroprotection therapy may optimally protect viable cells in the cortex measured using ATP levels as a marker. PMID:27180104

  4. Segmental Transarterial Embolization in a Translational Rat Model of Hepatocellular Carcinoma

    PubMed Central

    Gade, Terence P.F.; Hunt, Stephen J.; Harrison, Neil; Nadolski, Gregory J.; Weber, Charles; Pickup, Stephen; Furth, Emma E.; Schnall, Mitchell D.; Soulen, Michael C.; Simon, M. Celeste

    2016-01-01

    Purpose To develop a clinically relevant, minimally invasive technique for transarterial embolization in a translational rat model of hepatocellular carcinoma (HCC). Materials and Methods Oral diethylnitrosamine was administered to 53 male Wistar rats ad libitum for 12 weeks. Tumor induction was monitored using magnetic resonance imaging. Minimally invasive lobar or segmental transarterial embolization was performed through a left common carotid artery approach. Necropsy was performed to evaluate periprocedural mortality. Histologic analysis of tumors that received embolization was performed to assess percent tumor necrosis. Results Severe cirrhosis and autochthonous HCCs were characterized in a cohort of rats composed of two groups of rats identically treated with diethylnitrosamine with median survival times of 101 days and 105 days (n = 10/group). A second cohort was used to develop minimally invasive transarterial embolization of HCCs (n = 10). In a third cohort, lobar embolization was successfully performed in 9 of 10 rats and demonstrated a high rate of periprocedural mortality (n = 5). Necropsy performed for periprocedural mortality after lobar embolization demonstrated extensive tissue necrosis within the liver (n = 3) and lungs (n = 2), indicating nontarget embolization as the likely cause of mortality. In a fourth cohort of rats, a segmental embolization technique was successfully applied in 10 of 13 rats. Segmental embolization resulted in a reduction in periprocedural mortality (P = .06) relative to selective embolization and a 19% increase in average tumor necrosis (P = .04). Conclusions Minimally invasive, segmental embolization mimicking the currently applied clinical approach is feasible in a translational rat model of HCC and offers the critical advantage of reduced nontarget embolization relative to lobar embolization. PMID:25863596

  5. Embolic Stroke Caused by Staphylococcus lugdunensis Endocarditis Complicating Vasectomy in a 36-Year-Old Man

    PubMed Central

    Loftsgaarden, Megan; Chukwudelunzu, Felix

    2015-01-01

    Staphylococcus lugdunensis is part of the native flora in the inguinal region of the body. Inguinal surgeries, such as vasectomy, place carriers of this aggressive pathogen at risk for contamination. Native-valve endocarditis caused by coagulase-negative S. lugdunensis has a rapid and complicated clinical course. The pathogenicity of this organism is not limited to cardiac valvular destruction. We report the case of a 36-year-old man who presented with S. lugdunensis endocarditis, dysarthria, and hemiparesis 5 weeks after a vasectomy. To our knowledge, this is the first report of embolic stroke caused by S. lugdunensis endocarditis. In addition, we discuss the relevant medical literature. PMID:26664319

  6. Embolic Stroke Caused by Staphylococcus lugdunensis Endocarditis Complicating Vasectomy in a 36-Year-Old Man.

    PubMed

    David, Manova; Loftsgaarden, Megan; Chukwudelunzu, Felix

    2015-12-01

    Staphylococcus lugdunensis is part of the native flora in the inguinal region of the body. Inguinal surgeries, such as vasectomy, place carriers of this aggressive pathogen at risk for contamination. Native-valve endocarditis caused by coagulase-negative S. lugdunensis has a rapid and complicated clinical course. The pathogenicity of this organism is not limited to cardiac valvular destruction. We report the case of a 36-year-old man who presented with S. lugdunensis endocarditis, dysarthria, and hemiparesis 5 weeks after a vasectomy. To our knowledge, this is the first report of embolic stroke caused by S. lugdunensis endocarditis. In addition, we discuss the relevant medical literature. PMID:26664319

  7. Embolic Stroke as the Initial Manifestation of Systemic Lupus Erythematosus.

    PubMed

    Khan, Reshma M; Namas, Rajaie; Parikh, Sachin; Rubin, Bernard

    2015-01-01

    We present a case of a 21-year-old African-American female with no significant medical history, who presented to the emergency department with a one-week history of blurry and double vision. Ophthalmology evaluation revealed bilateral retinal artery occlusion. Further workup with imaging of the brain was consistent with an ischemic stroke. Hereditary hypercoagulable workup was unremarkable and initial testing for antiphospholipid syndrome was positive. She underwent transesophageal echocardiogram (TEE), which showed severe mitral regurgitation and thickening of mitral valve leaflets consistent with Libman-Sacks endocarditis. Autoimmune workup was positive for IF-ANA, anti-RNP, and anti-Smith antibody. She fulfilled 4/11 of the ACR criteria and met 5 of the SLICC (Systemic Lupus International Collaborating Clinics) criteria for lupus (nonscaring alopecia, thrombocytopenia, positive ANA, and positive anti-Smith and positive anti-phospholipid antibodies). This case highlights the importance of early recognition of underlying connective tissue diseases and timely management of these diseases in young patients with no previous manifestations of diseases. PMID:26266073

  8. Prevention of deep venous thrombosis and pulmonary embolism following stroke: a systematic review of published articles.

    PubMed

    André, C; de Freitas, G R; Fukujima, M M

    2007-01-01

    We performed a systematic review of the literature on venous thromboembolism (VTE) prophylaxis following cerebral infarct (CI) and haemorrhagic stroke. MEDLINE, Cochrane, LILACS and SciELO databases were scanned, and the Abstracts from Brazilian, American and European Neurology and Stroke Congresses were scrutinized for clinical trials. Moreover, the reference lists of articles and reviews were searched. A pooled analysis of two large studies with aspirin was made. Both unfractionated heparin and low molecular weight heparins/heparinoids (LMWH) are partially effective for VTE prophylaxis after CI, and should be routinely used in patients with motor deficit and reduced mobility and no contraindications. Reduction of deep venous thrombosis is better established than the effect over pulmonary embolism or mortality. Some evidence points to a greater efficacy of LMWH. The available evidence does not support the use of mechanical methods or dextran. Aspirin may have a mild protective effect. Low-dose Warfarin might be useful in the rehabilitation setting. Strict recommendations cannot be made in patients with haemorrhagic stroke but intermittent pneumatic compression merits further study. There are important limitations of current VTE preventive strategies following stroke. Additional studies on the combination of methods after CI and of low doses of anticoagulants following cerebral haemorrhage are urgently needed. PMID:17222109

  9. Pulmonary Embolism in Ischemic Stroke: Clinical Presentation, Risk Factors, and Outcome

    PubMed Central

    Pongmoragot, Jitphapa; Rabinstein, Alejandro A.; Nilanont, Yongchai; Swartz, Richard H.; Zhou, Limei; Saposnik, Gustavo

    2013-01-01

    Background Limited information is available on the frequency of pulmonary embolism (PE) in patients with an acute ischemic stroke (AIS). We evaluated clinical characteristics, predisposing factors, and outcomes in AIS patients with PE. Methods and Results We included all AIS patients admitted to participating institutions in the Registry of the Canadian Stroke Network. Clinically PE was documented by a physician and confirmed by computed tomography pulmonary angiography within 30 days of the stroke case index. The primary outcome was death or disability at discharge. Secondary outcomes included disposition, length of hospital stay, mortality at 3 months and 1 year. Among 11 287 patients with AIS, PE was found in 89 (0.78%) patients. History of cancer, deep vein thrombosis (DVT)/PE, and DVT during the hospitalization were associated with PE. PE was associated with higher risk of death at 30 days (25.8% versus 13.6%; P<0.001), at 1 year (47.2% versus 24.6%; P<0.001), and disability at discharge (85.4% versus 63.6%; P<0.001). Mean length of stay was longer in stroke patients with PE (36 versus 16 days; P=0.001). After adjusting for age, sex, and stroke severity, PE remained associated with lower survival at 30 days and 1 year, and death or disability at discharge (OR 3.02; 95% CI 1.56 to 5.83). Conclusions In this large cohort study, PE occurred in nearly 1% of AIS patients. PE was more common in patients with severe stroke, history of cancer, previous DVT/PE or acute DVT and associated with lower short‐ and long‐term survival, greater disability, and longer length of stay. PMID:24275627

  10. Acute stroke from paradoxical embolism of dense fibrous tissue following pacemaker lead extraction: salvation by mechanical thrombectomy.

    PubMed

    Dayal, Nicolas B; Narata, Ana Paula; Burri, Haran

    2016-02-01

    Systemic embolization is a dreaded complication of transvenous lead extraction (TLE), even without visible vegetations. Preoperative patent foramen ovale evaluation is important, justifying neurological surveillance or consideration of surgical extraction in selected cases. In case of stroke after TLE, mechanical thrombectomy is a successful therapy, and should be readily available. PMID:26862414

  11. When Coughing Can Cause Stroke - A Case-Based Update on Cerebral Air Embolism Complicating Biopsy of the Lung

    SciTech Connect

    Kau, Thomas Rabitsch, Egon; Celedin, Stefan; Habernig, Sandra M.; Weber, Joerg R.; Hausegger, Klaus A.

    2008-09-15

    Introducing gas to the circulation is a largely iatrogenic problem which can result in serious morbidity and even death. We report a case of CT-guided needle biopsy of a pulmonary lesion complicated by acute stroke. The English literature on cerebral air embolism is reviewed, including an update of current opinions on its pathomechanism, diagnostic findings, therapeutic strategies, and means of prevention.

  12. Piperlonguminine is neuroprotective in experimental rat stroke.

    PubMed

    Yang, Tiansong; Sun, Shixiao; Wang, Tiegang; Tong, Xin; Bi, Junhui; Wang, Yulin; Sun, Zhongren

    2014-12-01

    Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Piperlonguminine (PE) has been proved to have anti-inflammatory actions. In this study, we investigated the effects of PE on cultured neuronal cell line, SH-SY5Y in vitro and experimental rat ischemic stroke in vivo. For oxygen-glucose deprivation (OGD) and tumor necrosis factor-α (TNF-α) stimulated SH-SY5Y cell line in vitro, SH-SY5Y cells were incubated with PE. In vivo, rats were subjected to middle cerebral artery occlusion (MACO) for 1h, followed by reperfusion for 23 h. The results of this study showed that treatment of SH-SY5Y cells with PE reduced the OGD-induced cytotoxicity and apoptosis and blocked TNF-α-induced activation of NF-κB and MAPK. Intraperitoneal injection of PE (2.4 mg/kg) produced a significant neuroprotective potential in rats with cerebral ischemia. PE attenuated neurological deficit scores, brain infarct volume and brain water content in rats, and inhibited activation of NF-κB and MAPK. These data show that PE protects the brain against ischemic cerebral injury via alleviating blood-brain barrier (BBB) breakdown, which may be mediated via inhibiting NF-κB and MAPK signaling pathways. PMID:25257731

  13. Computational Assessment of the Relation Between Embolism Source and Embolus Distribution to the Circle of Willis for Improved Understanding of Stroke Etiology.

    PubMed

    Mukherjee, Debanjan; Jani, Neel D; Selvaganesan, Kartiga; Weng, Christopher L; Shadden, Shawn C

    2016-08-01

    Stroke caused by an embolism accounts for about a third of all stroke cases. Understanding the source and cause of the embolism is critical for diagnosis and long-term treatment of such stroke cases. The complex nature of the transport of an embolus within large arteries is a primary hindrance to a clear understanding of embolic stroke etiology. Recent advances in medical image-based computational hemodynamics modeling have rendered increasing utility to such techniques as a probe into the complex flow and transport phenomena in large arteries. In this work, we present a novel, patient-specific, computational framework for understanding embolic stroke etiology, by combining image-based hemodynamics with discrete particle dynamics and a sampling-based analysis. The framework allows us to explore the important question of how embolism source manifests itself in embolus distribution across the various major cerebral arteries. Our investigations illustrate prominent numerical evidence regarding (i) the size/inertia-dependent trends in embolus distribution to the brain; (ii) the relative distribution of cardiogenic versus aortogenic emboli among the anterior, middle, and posterior cerebral arteries; (iii) the left versus right brain preference in cardio-emboli and aortic-emboli transport; and (iv) the source-destination relationship for embolisms affecting the brain. PMID:27367268

  14. Angiotensin receptor antagonists delay nitric oxide-deficient stroke in stroke-prone rats.

    PubMed

    Ahmad, S

    1997-08-20

    We investigated whether chronic deficiency of nitric oxide (NO) in stroke-prone spontaneously hypertensive rats (SHRSP) precipitates stroke and whether exogenous nitrates and other pharmacological agents can prevent stroke. Groups of five-week-old male SHRSP rats chronically received saline, L-nitro-arginine methyl ester (L-NAME) in saline, L-NAME along with pharmacological agents (L-arginine, isosorbide dinitrate, enalapril maleate and L-158,809; angiotensin receptor antagonist; 5,7-dimethyl-2-ethyl-3(-)[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]meth yl]-imidazo[4,5-b]pyridine) in saline to drink. The development of visible neurological deficits following various treatments was considered as an occurrence of stroke. Within hours following onset of stroke, the rats were anesthetized, catheterized and attached to a Cardiomax blood pressure recorder. SHRSP treated with L-NAME (10+/-2 mg/day) developed stroke in 11+/-2 days while no neurological deficit was seen in animals receiving saline till the end of the study period (35 days). Blockade of the renin-angiotensin system with enalapril or L-158,809 significantly delayed the onset of stroke (19+/-2 and 20+/-2 days, respectively), but caused only slight reductions in mean arterial blood pressure. These results suggest that chronic inhibition of NO synthase in SHRSP is associated with the development of stroke and such stroke appears to be renin-angiotensin system-dependent. PMID:9311659

  15. Molecular MRI of intracranial thrombus in a rat ischemic stroke model

    PubMed Central

    Uppal, Ritika; Ay, Ilknur; Dai, Guangping; Kim, Young Ro; Sorensen, A. Gregory; Caravan, Peter

    2010-01-01

    Background and Purpose Intracranial thrombus is a principal feature in most ischemic stroke, and thrombus location and size may correlate with outcome and response to thrombolytic therapy. EP-2104R, a fibrin-specific molecular MR agent, was previously shown to enhance extracranial thrombi in animal models and recently, in clinical trials. The purpose of this work was to determine if a fibrin-specific molecular MR probe could noninvasively characterize intracranial thrombi. Methods Embolic stroke was induced in adult rats by occlusion of the right internal carotid artery with an aged thrombus. Diffusion weighted imaging, time of flight angiography, and high resolution three dimensional T1-weighted MRI were performed at 4.7T prior to and following contrast agents EP-2104R (10 µmol/kg, n=6) or Gd-DTPA (200 µmol/kg, control, n=5). Gd levels in thrombus, brain, and blood were determined by ex vivo elemental analysis. Results In all animals, MR angiography revealed a flow deficit and diffusion-weighted imaging showed a hyperintensity consistent with ischemia. EP-2104R-enhanced MRI resulted in visualization of all occlusive thrombi (6/6) as well as vessel wall enhancement in all 6 animals with high contrast to noise relative to blood (10.7 post EP-2104R vs. 0.54 pre, p<0.0001). Gd-DTPA injected animals showed no occlusive thrombus or vessel wall enhancement (0/5). The concentration of Gd in the thrombus post-EP2104 was 18 times that in the blood pool. Conclusions EP-2104R enhanced MRI successfully identifies intracranial thrombus in a rat embolic stroke model. PMID:20395615

  16. Posterior Circulation Stroke After Bronchial Artery Embolization. A Rare but Serious Complication

    SciTech Connect

    Laborda, Alicia; Tejero, Carlos; Fredes, Arturo; Cebrian, Luis; Guelbenzu, Santiago; Gregorio, Miguel Angel de

    2013-06-15

    Bronchial artery embolization (BAE) is the treatment of choice for massive hemoptysis with rare complications that generally are mild and transient. There are few references in the medical literature with acute cerebral embolization as a complication of BAE. We report a case of intracranial posterior territory infarctions as a complication BAE in a patient with hemoptysis due to bronchiectasis.

  17. Alpha 1-Antitrypsin Therapy Mitigated Ischemic Stroke Damage in Rats

    PubMed Central

    Moldthan, Huong L.; Hirko, Aaron C.; Thinschmidt, Jeffrey S.; Grant, Maria; Li, Zhimin; Peris, Joanna; Lu, Yuanqing; Elshikha, Ahmed; King, Michael A.; Hughes, Jeffrey A.; Song, Sihong

    2014-01-01

    Currently, the only effective therapy for acute ischemic stroke is the thrombolytic agent recombinant tissue plasminogen activator. α1-Antitrypsin, an endogenous inhibitor of serine proteinases and a primary acute phase protein with potent anti-inflammatory, anti-apoptotic, antimicrobial and cytoprotective activities, could be beneficial in stroke.. The goal of this study was to test whether α1-antitrypsin could improve ischemic stroke outcome in an established rat model. Middle cerebral artery occlusion was induced in male rats via intracranial microinjection of endothelin-1. Five to ten minutes following stroke induction rats received either intracranial or intravenous delivery of human α1-antitrypsin. Cylinder and vibrissae tests were used to evaluate sensorimotor function before and 72 hours after middle cerebral artery occlusion. Infarct volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or magnetic resonance imaging 72 hours after middle cerebral artery occlusion. Despite equivalent initial strokes, at 72 hours the infarct volumes of the human α1-antitrypsin treatment groups (local and systemic injection) were statistically significantly reduced by 83% and 63% (p<0.0001 and p < 0.05 respectively) compared with control rats. Human α1-antitrypsin significantly limited sensory motor systems deficits. Human α1-antitrypsin could be a potential novel therapeutic drug for the protection against neurodegeneration following ischemic stroke, but more studies are needed to investigate the protective mechanisms and efficacy in other animal models. PMID:24582784

  18. Continual Gram-negative bacterial challenge accelerates stroke onset in stroke-prone spontaneously hypertensive rats.

    PubMed

    Kawato, Takayuki; Tanaka, Hideki; Tabuchi, Masaki; Ooshima, Kana; Nakai, Kumiko; Yamashita, Yoshihisa; Maeno, Masao

    2013-01-01

    This study examined the effects of continual Gram-negative bacterial challenge on stroke onset. Stroke onset occurred significantly earlier in stroke-prone spontaneously hypertensive rats (SHRSP) injected with a bacterial cell suspension of Gram-negative rods or lipopolysaccharides (LPSs) than in uninjected controls. Paralysis of the hindlimb, piloerection, hypokinesis, and hyperkinesis were observed in LPS-injected SHRSP but not in uninjected controls during stroke onset. The serum levels of NOx, thiobarbituric acid reactive substance, and 8-hydroxydeoxyguanosine increased in LPS-injected SHRSP. These results suggest that continual Gram-negative bacterial challenge induces accelerated stroke onset in SHRSP, probably caused by oxidative stress responses derived from LPSs. PMID:22630606

  19. Increased Visceral Adipose Tissue as a Potential Risk Factor in Patients with Embolic Stroke of Undetermined Source (ESUS)

    PubMed Central

    Muuronen, Antti T.; Taina, Mikko; Hedman, Marja; Marttila, Jarkko; Kuusisto, Johanna; Onatsu, Juha; Vanninen, Ritva; Jäkälä, Pekka; Sipola, Petri; Mustonen, Pirjo

    2015-01-01

    Purpose The etiology of an ischemic stroke remains undetermined in 20–35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke. Methods Altogether 58 patients (mean age 57.7±10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered. Results Mean VAT area was significantly higher in stroke patients (205±103 cm2 for men and 168±99 cm2 for women) compared to all reference populations (P<0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors. Conclusion Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients. PMID:25756793

  20. The macrosphere model—an embolic stroke model for studying the pathophysiology of focal cerebral ischemia in a translational approach

    PubMed Central

    Rueger, Maria Adele

    2015-01-01

    The main challenge of stroke research is to translate promising experimental findings from the bench to the bedside. Many suggestions have been made how to achieve this goal, identifying the need for appropriate experimental animal models as one key issue. We here discuss the macrosphere model of focal cerebral ischemia in the rat, which closely resembles the pathophysiology of human stroke both in its acute and chronic phase. Key pathophysiological processes such as brain edema, cortical spreading depolarizations (CSD), neuroinflammation, and stem cell-mediated regeneration are observed in this stroke model, following characteristic temporo-spatial patterns. Non-invasive in vivo imaging allows studying the macrosphere model from the very onset of ischemia up to late remodeling processes in an intraindividual and longitudinal fashion. Such a design of pre-clinical stroke studies provides the basis for a successful translation into the clinic. PMID:26207251

  1. Stroke

    MedlinePlus

    ... Stay Connected Home » Stroke Heath and Aging Stroke What Is a Stroke? Stroke Is an Emergency. ... IGNORE THE SIGNS OF STROKE! What Is a Stroke? A stroke happens when something changes how blood ...

  2. Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study

    PubMed Central

    Dalichampt, Marie; Raguideau, Fanny; Ricordeau, Philippe; Blotière, Pierre-Olivier; Rudant, Jérémie; Alla, François; Zureik, Mahmoud

    2016-01-01

    Objective To assess the risk of pulmonary embolism, ischaemic stroke, and myocardial infarction associated with combined oral contraceptives according to dose of oestrogen (ethinylestradiol) and progestogen. Design Observational cohort study. Setting Data from the French national health insurance database linked with data from the French national hospital discharge database. Participants 4 945 088 women aged 15-49 years, living in France, with at least one reimbursement for oral contraceptives and no previous hospital admission for cancer, pulmonary embolism, ischaemic stroke, or myocardial infarction, between July 2010 and September 2012. Main outcome measures Relative and absolute risks of first pulmonary embolism, ischaemic stroke, and myocardial infarction. Results The cohort generated 5 443 916 women years of oral contraceptive use, and 3253 events were observed: 1800 pulmonary embolisms (33 per 100 000 women years), 1046 ischaemic strokes (19 per 100 000 women years), and 407 myocardial infarctions (7 per 100 000 women years). After adjustment for progestogen and risk factors, the relative risks for women using low dose oestrogen (20 µg v 30-40 µg) were 0.75 (95% confidence interval 0.67 to 0.85) for pulmonary embolism, 0.82 (0.70 to 0.96) for ischaemic stroke, and 0.56 (0.39 to 0.79) for myocardial infarction. After adjustment for oestrogen dose and risk factors, desogestrel and gestodene were associated with statistically significantly higher relative risks for pulmonary embolism (2.16, 1.93 to 2.41 and 1.63, 1.34 to 1.97, respectively) compared with levonorgestrel. Levonorgestrel combined with 20 µg oestrogen was associated with a statistically significantly lower risk than levonorgestrel with 30-40 µg oestrogen for each of the three serious adverse events. Conclusions For the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial

  3. Sleep deprivation attenuates experimental stroke severity in rats.

    PubMed

    Moldovan, Mihai; Constantinescu, Alexandra Oana; Balseanu, Adrian; Oprescu, Nicoleta; Zagrean, Leon; Popa-Wagner, Aurel

    2010-03-01

    Indirect epidemiological and experimental evidence suggest that the severity of injury during stroke is influenced by prior sleep history. The aim of our study was to test the effect of acute sleep deprivation on early outcome following experimental stroke. Young male Sprague-Dawley rats (n=20) were subjected to focal cerebral ischemia by reversible right middle cerebral artery occlusion (MCAO) for 90 min. In 10 rats, MCAO was performed just after 6-h of total sleep deprivation (TSD) by "gentle handling", whereas the other rats served as controls. Neurological function during the first week after stroke was monitored using a battery of behavioral tests investigating the asymmetry of sensorimotor deficit (tape removal test and cylinder test), bilateral sensorimotor coordination (rotor-rod and Inclined plane) and memory (T-maze and radial maze). Following MCAO, control rats had impaired behavioral performance in all tests. The largest impairment was noted in the tape test where the tape removal time from the left forelimb (contralateral to MCAO) was increased by approximately 10 fold (p<0.01). In contrast, rats subjected to TSD had complete recovery of sensorimotor performance consistent with a 2.5 fold smaller infarct volume and reduced morphological signs of neuronal injury at day 7 after MCAO. Our data suggest that brief TSD induces a neuroprotective response that limits the severity of a subsequent stroke, similar to rapid ischemic preconditioning. PMID:20045410

  4. Left atrial enlargement is an independent predictor of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

    PubMed

    Hamatani, Yasuhiro; Ogawa, Hisashi; Takabayashi, Kensuke; Yamashita, Yugo; Takagi, Daisuke; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru; Lip, Gregory Y H; Akao, Masaharu

    2016-01-01

    Controversy exists regarding whether left atrial enlargement (LAE) is a predictor of stroke/systemic embolism (SE) in atrial fibrillation (AF) patients. The Fushimi AF Registry, a community-based prospective survey, enrolled all AF patients in Fushmi-ku, Japan, from March 2011. Follow-up data and baseline echocardiographic data were available for 2,713 patients by August 2015. We compared backgrounds and incidence of events over a median follow-up of 976.5 days between patients with LAE (left atrial diameter > 45 mm; LAE group) and those without in the Fushimi AF Registry. The LAE group accounted for 39% (n = 1,049) of cohort. The LAE group was older and had longer AF duration, with more prevalent non-paroxysmal AF, higher CHADS2/CHA2DS2-VASc score, and oral anticoagulant (OAC) use. A higher risk of stroke/SE during follow-up in the LAE group was found (entire cohort; hazard ratio (HR): 1.92, 95% confidence interval (CI): 1.40-2.64; p < 0.01; without OAC; HR: 1.97, 95% CI: 1.18-3.25; p < 0.01; with OAC; HR: 1.83, 95% CI: 1.21-2.82; p < 0.01). LAE was independently associated with increased risk of stroke/SE (HR: 1.74, 95% CI: 1.25-2.42; p < 0.01) after adjustment by the components of CHA2DS2-VASc score and OAC use. In conclusion, LAE was an independent predictor of stroke/SE in large community cohort of AF patients. PMID:27485817

  5. Left atrial enlargement is an independent predictor of stroke and systemic embolism in patients with non-valvular atrial fibrillation

    PubMed Central

    Hamatani, Yasuhiro; Ogawa, Hisashi; Takabayashi, Kensuke; Yamashita, Yugo; Takagi, Daisuke; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru; Lip, Gregory Y. H.; Akao, Masaharu

    2016-01-01

    Controversy exists regarding whether left atrial enlargement (LAE) is a predictor of stroke/systemic embolism (SE) in atrial fibrillation (AF) patients. The Fushimi AF Registry, a community-based prospective survey, enrolled all AF patients in Fushmi-ku, Japan, from March 2011. Follow-up data and baseline echocardiographic data were available for 2,713 patients by August 2015. We compared backgrounds and incidence of events over a median follow-up of 976.5 days between patients with LAE (left atrial diameter > 45 mm; LAE group) and those without in the Fushimi AF Registry. The LAE group accounted for 39% (n = 1,049) of cohort. The LAE group was older and had longer AF duration, with more prevalent non-paroxysmal AF, higher CHADS2/CHA2DS2-VASc score, and oral anticoagulant (OAC) use. A higher risk of stroke/SE during follow-up in the LAE group was found (entire cohort; hazard ratio (HR): 1.92, 95% confidence interval (CI): 1.40–2.64; p < 0.01; without OAC; HR: 1.97, 95% CI: 1.18–3.25; p < 0.01; with OAC; HR: 1.83, 95% CI: 1.21–2.82; p < 0.01). LAE was independently associated with increased risk of stroke/SE (HR: 1.74, 95% CI: 1.25–2.42; p < 0.01) after adjustment by the components of CHA2DS2-VASc score and OAC use. In conclusion, LAE was an independent predictor of stroke/SE in large community cohort of AF patients. PMID:27485817

  6. MRI evaluation of BBB disruption after adjuvant AcSDKP treatment of stroke with tPA in rat.

    PubMed

    Ding, G; Zhang, Z; Chopp, M; Li, L; Zhang, L; Li, Q; Wei, M; Jiang, Q

    2014-06-20

    The primary limitation of thrombolytic treatment of ischemic stroke with tissue plasminogen activator (tPA) is the hemorrhagic risk. We tested AcSDKP (N-acetyl-seryl-aspartyl-lysyl-proline), as an auxiliary therapeutic agent, to reduce blood-brain barrier (BBB) disruption in a combination tPA thrombolytic treatment of stroke. Wistar rats subjected to embolic stroke were randomly assigned to either the tPA monotherapy group (n=9) or combination of tPA and AcSDKP treatment group (n=9) initiated at 4 h after ischemia. Magnetic resonance imaging (MRI) measurements were performed before and after the treatments. Immunohistochemical staining and measurements were performed to confirm MRI findings. Longitudinal MRI permeability measurements with gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) demonstrated that combination treatment of acute embolic stroke with AcSDKP and tPA significantly reduced BBB leakage, compared to tPA monotherapy, at 3 and 6 days (18.3±9.8 mm3 vs. 65.0±21.0 mm3, p<0.001) after the onset of stroke, although BBB leakage was comparable between the two groups prior to the treatments (6.8±4.4 mm3 vs. 4.3±3.3 mm3, p>0.18). The substantial reduction of BBB leakage observed in the combination treatment group was closely associated with reduced ischemic lesions measured by T2 maps (113.6±24.9 mm3 vs. 188.1±60.8 mm3, p<0.04 at 6 days). Histopathological analysis of the same population of rats showed that the combination treatment significantly reduced parenchymal fibrin deposition (0.063±0.059 mm2 vs. 0.172±0.103 mm2, p<0.03) and infarct volume (146.7±35.9 mm3 vs. 199.3±60.4 mm3, p<0.05) compared to the tPA monotherapy at 6days after stroke. MRI provides biological insight into the therapeutic benefit of combination treatment of stroke with tPA and AcSDKP 4h after onset, and demonstrates significantly improved cerebrovascular integrity with neuroprotective effects compared with tPA monotherapy. PMID:24769225

  7. High-Intensity Focused Ultrasound (HIFU) for Dissolution of Clots in a Rabbit Model of Embolic Stroke

    PubMed Central

    Burgess, Alison; Huang, Yuexi; Waspe, Adam C.; Ganguly, Milan; Goertz, David E.; Hynynen, Kullervo

    2012-01-01

    It is estimated that only 2–6% of patients receive thrombolytic therapy for acute ischemic stroke suggesting that alternative therapies are necessary. In this study, we investigate the potential for high intensity focused ultrasound (HIFU) to initiate thrombolysis in an embolic model of stroke. Iron-loaded blood clots were injected into the middle cerebral artery (MCA) of New Zealand White rabbits, through the internal carotid artery and blockages were confirmed by angiography. MRI was used to localize the iron-loaded clot and target the HIFU beam for treatment. HIFU pulses (1.5 MHz, 1 ms bursts, 1 Hz pulse repetition frequency, 20 s duration) were applied to initiate thrombolysis. Repeat angiograms and histology were used to assess reperfusion and vessel damage. Using 275 W of acoustic power, there was no evidence of reperfusion in post-treatment angiograms of 3 rabbits tested. In a separate group of animals, 415 W of acoustic power was applied and reperfusion was observed in 2 of the 4 (50%) animals treated. In the last group of animals, acoustic power was further increased to 550 W, which led to the reperfusion in 5 of 7 (∼70%) animals tested. Histological analysis confirmed thatthe sonicated vessels remained intact after HIFU treatment. Hemorrhage was detected outside of the sonication site, likely due to the proximity of the target vessel with the base of the rabbit skull. These results demonstrate the feasibility of using HIFU, as a stand-alone method, to cause effective thrombolysis without immediate damage to the targeted vessels. HIFU, combined with imaging modalities used to identify and assess stroke patients, could dramatically reduce the time to achieve flow restoration in patients thereby significantly increasing the number of patients which benefit from thrombolysis treatments. PMID:22870315

  8. Interleaved imaging of cerebral hemodynamics and blood flow index to monitor ischemic stroke and treatment in rat by volumetric diffuse optical tomography

    PubMed Central

    Lin, Zi-Jing; Ren, Ming; Li, Lin; Liu, Yueming; Su, Jianzhong; Yang, Shao-Hua; Liu, Hanli

    2013-01-01

    Diffuse optical tomography (DOT) has been used by several groups to assess cerebral hemodynamics of cerebral ischemia in humans and animals. In this study, we combined DOT with an indocyanine green (ICG)-tracking method to achieve interleaved images of cerebral hemodynamics and blood flow index (BFI) using two middle cerebral artery occlusion (MCAO) rat models. To achieve volumetric images with high-spatial resolution, we first integrated a depth compensation algorithm (DCA) with a volumetric mesh-based rat head model to generate three-dimensional (3D) DOT on a rat brain atlas. Then, the experimental DOT data from two rat models were collected using interleaved strategy for cerebral hemodynamics and BFI during and after ischemic stroke, with and without a thrombolytic therapy for the embolic MCAO model. The acquired animal data were further analyzed using the integrated rat-atlas-guided DOT method to form time-evolving 3D images of both cerebral hemodynamics and BFI. In particular, we were able to show and identify therapeutic outcomes of a thrombolytic treatment applied to the embolism-induced ischemic model. This paper demonstrates that volumetric DOT is capable of providing high-quality, interleaved images of cerebral hemodynamics and blood perfusion in small animals during and after ischemic stroke, with excellent 3D visualization and quantifications. PMID:23872158

  9. Interleaved imaging of cerebral hemodynamics and blood flow index to monitor ischemic stroke and treatment in rat by volumetric diffuse optical tomography.

    PubMed

    Lin, Zi-Jing; Ren, Ming; Li, Lin; Liu, Yueming; Su, Jianzhong; Yang, Shao-Hua; Liu, Hanli

    2014-01-15

    Diffuse optical tomography (DOT) has been used by several groups to assess cerebral hemodynamics of cerebral ischemia in humans and animals. In this study, we combined DOT with an indocyanine green (ICG)-tracking method to achieve interleaved images of cerebral hemodynamics and blood flow index (BFI) using two middle cerebral artery occlusion (MCAO) rat models. To achieve volumetric images with high-spatial resolution, we first integrated a depth compensation algorithm (DCA) with a volumetric mesh-based rat head model to generate three-dimensional (3D) DOT on a rat brain atlas. Then, the experimental DOT data from two rat models were collected using interleaved strategy for cerebral hemodynamics and BFI during and after ischemic stroke, with and without a thrombolytic therapy for the embolic MCAO model. The acquired animal data were further analyzed using the integrated rat-atlas-guided DOT method to form time-evolving 3D images of both cerebral hemodynamics and BFI. In particular, we were able to show and identify therapeutic outcomes of a thrombolytic treatment applied to the embolism-induced ischemic model. This paper demonstrates that volumetric DOT is capable of providing high-quality, interleaved images of cerebral hemodynamics and blood perfusion in small animals during and after ischemic stroke, with excellent 3D visualization and quantifications. PMID:23872158

  10. [Histostructural changes of rat cerebral cortex during hemorrhagic stroke modeling].

    PubMed

    Savos'ko, S I; Chaĭkovs'kyĭ, Iu B; Pogoriela, N Kh; Makarenko, O M

    2012-01-01

    Pathological changes during modeling of primary and secondary acute hemorrhagic stroke were studied in rats. We revealed differences in the activity of pharmacological action of medications under condition of acute stroke. The action of medications increased viability of neurons in both hemispheres of rat cerebrum at a right-side primary and secondary hemorrhagic stroke. Following secondary stroke, the amount of degenerative neurons amounted 25.5 +/- 0.8 cells/mm2, following the action ofcerebrolysin this value was 17.6 +/- 1.7 cells/ mm2 and after the action of cortexine and cerebral this value amounted 18.0 +/- 0.9 cells/mm2 and 10.7 +/- 0.4 cells/ mm2, respectively. In control animals the number of degenerative neurons did not exceed 2% and averaged 1.5 +/- 0.1 cells/mm2. Analysis of the morphological and statistical data showed that the most effective remedies under the primary and secondary hemorrhagic insult are cortexine and cerebral. Cerebral was found to be more effective. PMID:23233944

  11. Major ischaemic stroke caused by an air embolism from a ruptured giant pulmonary bulla.

    PubMed

    Gudmundsdottir, Johanna F; Geirsson, Arnar; Hannesson, Petur; Gudbjartsson, Tomas

    2015-01-01

    We report an extremely rare complication of a major ischaemic cerebral event caused by an air embolism due to spontaneous rupture of a giant pulmonary bulla that occurred during an airline flight. Shortly after take-off, the patient experienced sudden right-sided hemiplegia and dyspnoea. Following an emergency landing in Reykjavik, a CT scan of the brain showed minute air bubbles consistent with air emboli within the left-sided intracerebral arteries, and MRI showed signs of acute ischaemic cerebral infarction in the left hemisphere. The patient later underwent a pulmonary lobectomy and survived this life-threatening complication with relatively mild neurological sequelae. PMID:25743863

  12. Dynamics of neuroinflammation in the macrosphere model of arterio-arterial embolic focal ischemia: an approximation to human stroke patterns

    PubMed Central

    2010-01-01

    Background Neuroinflammation evolves as a multi-facetted response to focal cerebral ischemia. It involves activation of resident glia cell populations, recruitment of blood-derived leucocytes as well as humoral responses. Among these processes, phagocyte accumulation has been suggested to be a surrogate marker of neuroinflammation. We previously assessed phagocyte accumulation in human stroke by MRI. We hypothesize that phagocyte accumulation in the macrosphere model may resemble the temporal and spatial patterns observed in human stroke. Methods In a rat model of permanent focal ischemia by embolisation of TiO2-spheres we assessed key features of post-ischemic neuroinflammation by the means of histology, immunocytochemistry of glial activation and influx of hematogeneous cells, and quantitative PCR of TNF-α, IL-1, IL-18, and iNOS mRNA. Results In the boundary zone of the infarct, a transition of ramified microglia into ameboid phagocytic microglia was accompanied by an up-regulation of MHC class II on the cells after 3 days. By day 7, a hypercellular infiltrate consisting of activated microglia and phagocytic cells formed a thick rim around the ischemic infarct core. Interestingly, in the ischemic core microglia could only be observed at day 7. TNF-α was induced rapidly within hours, IL-1β and iNOS peaked within days, and IL-18 later at around 1 week after ischemia. Conclusions The macrosphere model closely resembles the characteristical dynamics of postischemic inflammation previously observed in human stroke. We therefore suggest that the macrosphere model is highly appropriate for studying the pathophysiology of stroke in a translational approach from rodent to human. PMID:21171972

  13. Choice of diet impacts the incidence of stroke-related symptoms in the spontaneously hypertensive stroke-prone rat model.

    PubMed

    Slemmer, Jennifer E; Shaughnessy, Kevin S; Scanlan, Adam P; Sweeney, Marva I; Gottschall-Pass, Katherine T

    2012-02-01

    The spontaneously hypertensive stroke-prone (SHRSP) rat is a commonly used model of cerebrovascular disease and hypertension. SHRSP rats have been shown to develop stroke-related symptoms (SRS) by age 14 weeks when fed a purified diet, such as AIN-93G, supplemented with 1% NaCl. We conducted a pathology pilot study to compare the incidence of SRS in SHRSP rats fed either AIN-93G (with 1% NaCl in drinking water) or commercially available rat chow (with 4% NaCl in the diet), starting at 8 weeks of age. These results prompted us to analyze data from 5 earlier feeding trials using SHRSP rats. Overall, we found that SHRSP rats fed AIN-93G purified diet for 8 or 17 weeks did not demonstrate SRS (n = 18), whereas all SHRSP rats fed lab chow exhibited SRS at age 15.1 ± 0.6 weeks (n = 23). In addition, SHRSP rats fed lab chow had decreased mass gain starting at age 13 weeks, as well as decreased feed efficiencies after the first 5 weeks of feeding (p < 0.05). In conclusion, our data suggest that diet composition is a major contributor to the onset of stroke in SHRSP rats and that diet choice should be critically evaluated based on endpoint measures in the SHRSP model. PMID:22316284

  14. Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

    PubMed

    Spencer, Ryan J; Amerena, John V

    2015-12-01

    Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF. PMID:26062914

  15. Stroke

    MedlinePlus

    ... the blockages that lead to ischemic strokes. A hemorrhagic stroke occurs if an artery in the brain leaks ... risms) are examples of conditions that can cause hemorrhagic strokes. (Aneurysms are balloon-like bulges in an artery ...

  16. Stroke

    MedlinePlus

    ... to a hospital quickly to begin treatment. Acute stroke therapies try to stop a stroke while it is ... rehabilitation helps individuals overcome disabilities that result from stroke damage. Drug therapy with blood thinners is the most common treatment ...

  17. Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI.

    PubMed

    Ding, Guangliang; Chen, Jieli; Chopp, Michael; Li, Lian; Yan, Tao; Li, Qingjiang; Cui, Chengcheng; Davarani, Siamak P N; Jiang, Quan

    2016-01-01

    Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x106, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05) decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T1-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T2 maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI. PMID:26900843

  18. Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI

    PubMed Central

    Ding, Guangliang; Chen, Jieli; Chopp, Michael; Li, Lian; Yan, Tao; Li, Qingjiang; Cui, Chengcheng; Davarani, Siamak P. N.; Jiang, Quan

    2016-01-01

    Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x106, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05) decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T1-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T2 maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI. PMID:26900843

  19. Effects of delayed treatment with nafronyl oxalate on microsphere embolism-induced changes in monoamine levels of rat brain regions.

    PubMed Central

    Takagi, N.; Miyake, K.; Ohiwa, A.; Nukaga, R.; Takeo, S.

    1996-01-01

    1. The present study was undertaken to examine the effects of delayed treatment with nafronyl oxalate (nafronyl), a cerebral vasodilator, on monoamine neurotransmitters of brain regions in the microsphere-embolized rat. 2. Microsphere embolism was induced by injecting 900 microspheres with a diameter of 48 microns into the right internal carotid artery of rats. Microsphere-embolized rats were treated with nafronyl, 15 mg kg-1, i.p., twice daily from the first to the 5th day. Levels of monoamines and their metabolites in the cerebral cortex, striatum, and hippocampus were measured on days 3 and 5 after the operation by a high-performance liquid chromatograph with electrochemical detection. In vivo tyrosine or tryptophan hydroxylation was estimated by measurement of the accumulation of 3, 4-dihydroxyphenylalanine or 5-hydroxy-1-tryptophan after administration of 3-hydroxybenzylhydrazine dihydrochloride, an inhibitor of aromatic L-amino acid decarboxylase. 3. Microsphere embolism induced decreases in dopamine, noradrenaline and 5-hydroxytryptamine in three brain regions of the right hemisphere on days 3 and 5. In the left hemisphere, the monoamines were reduced, but to a lesser degree than in the right hemisphere. On days 3 and 5, the decrease in the monoamines of the right hemisphere was attenuated by nafronyl treatment except for noradrenaline on day 3. The decrease in the monoamines levels in the left hemisphere was almost completely prevented by nafronyl treatment. 4. On day 3 after microsphere embolism, in vivo tyrosine and tryptophan hydroxylation was lower than the pre-embolic value in all three brain regions. Treatment of the embolized rats with nafronyl significantly attenuated the decrease in in vivo tyrosine and tryptophan hydroxylation in the ipsilateral hemisphere, but not hippocampal tryptophan hydroxylation. 5. The results suggested that treatment with nafronyl improves or attenuates changes in monoamine neurotransmitter metabolism of the brain regions

  20. SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats

    PubMed Central

    2012-01-01

    Background Stachybotrys microspora triprenyl phenols (SMTPs) are a novel family of small molecules that enhance both activation and fibrin-binding of plasminogen. While their effects on fibrinolysis have been characterized in vitro, little is known about their activity in vivo with respect to plasminogen activation and blood clot clearance. Results To select a potent SMTP congener for the evaluation of its action in vitro and in vivo, we tested several SMTP congeners with distinct structural properties for their effects on plasminogen activation. As a result, SMTP-7 (orniplabin) was found to have distinguished activity. Several lines of biochemical evidence supported the idea that SMTP-7 acted as a plasminogen modulator. SMTP-7 elevated plasma level of plasmin-α2-antiplasmin complex, an index of plasmin formation in vivo, 1.5-fold in mice after the intravenous injections at doses of 5 and 10 mg kg-1. In a rat pulmonary embolism model, SMTP-7 (5 mg kg-1) enhanced the rate of clot clearance ~3-fold in the absence of exogenous plasminogen activator. Clot clearance was enhanced further by 5 mg kg-1 of SMTP-7 in combination with single-chain urokinase-type plasminogen activator. Conclusions Our results show that SMTP-7 is a superior plasminogen modulator among the SMTP family compounds and suggest that the agent enhances plasmin generation in vivo, leading to clearance of thrombi in a model of pulmonary embolism. PMID:22230042

  1. Behavioral outcome measures used for human neural stem cell transplantation in rat stroke models

    PubMed Central

    Jensen, Matthew B.; Han, Dong Y.; Sawaf, Abdullah Al; Krishnaney-Davison, Rajeev

    2011-01-01

    Stroke is a leading cause of death and disability, leading to the development of various stroke models to test new treatments, most commonly in the rat. Human stroke trials focus on disability, related primarily to neurological deficits. To better model the clinical application of these treatments, many behavioral tests have been developed using the rat stroke model. We performed a systematic review of all the behavioral outcome measures used in published studies of human neural stem cell transplantation in rat stroke models. The reviewed tests include motor, sensory, cognitive, activity, and combination tests. For each test, we give a brief description, trace the origin of the test, and discuss test performance in the reviewed studies. We conclude that while many behavioral tests are available for this purpose, there does not appear to be consensus on an optimal testing strategy. PMID:22053257

  2. Effects of naftidrofuryl oxalate on microsphere embolism-induced decrease in regional blood flow of rat brain.

    PubMed Central

    Miyake, K.; Takagi, N.; Takeo, S.

    1994-01-01

    1. The purpose of the present study was to determine whether naftidrofuryl oxalate (naftidrofuryl), a vasodilator, is capable of improving brain regional blood flow of animals in sustained ischaemia. 2. Cerebral ischaemia was induced by injecting 900 microspheres (48 microns in diameter) into the right internal carotid artery of rats. Cerebral blood flow of brain regions was measured by a hydrogen clearance method on the 3rd, 7th and 28th days after the onset of ischaemia. Ischaemic animals were treated with naftidrofuryl, 15 mg kg-1 day-1 i.p., from the first to 28th day. 3. Microsphere-embolism caused a sustained decrease in cortical and striatal blood flow over a period of 28 days, whereas hippocampal blood flow was decreased on the 3rd day but not on the 7th or 28th day. On the 3rd day, the striatal and hippocampal but not cortical blood flow of naftidrofuryl-treated, microsphere-embolized rats was higher than untreated rats. On the 7th and 28th days, the cortical and striatal blood flow of the treated and untreated animals did not differ. 4. Brain slices from microsphere-embolized rats contained areas, which were not stained with triphenyltetrazolium chloride (TTC), to a similar degree on the 3rd, 7th and 28th days, indicating the genesis of cerebral infarction. TTC-unstained areas of microsphere-embolized rats that had received naftidrofuryl treatment were smaller than those of untreated rats on the 3rd and 7th days, but not on the 28th day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8032646

  3. Stroke

    MedlinePlus

    ... emergency. Strokes happen when blood flow to your brain stops. Within minutes, brain cells begin to die. There are two kinds ... blocks or plugs a blood vessel in the brain. The other kind, called hemorrhagic stroke, is caused ...

  4. Stroke

    MedlinePlus Videos and Cool Tools

    ... part of the body and lodges within an artery in the brain. When an internal arterial wall ... an embolism is formed in the internal carotid artery, breaks loose, travels towards the brain and lodges ...

  5. Stroke

    MedlinePlus

    ... a clot within a blood vessel of the brain or neck, called thrombosis the movement of a clot from ... body, such as from the heart to the neck or brain, called an embolism a severe narrowing of an ...

  6. Bone marrow stromal cells inhibits HMGB1-mediated inflammation after stroke in type 2 diabetic rats.

    PubMed

    Hu, J; Liu, B; Zhao, Q; Jin, P; Hua, F; Zhang, Z; Liu, Y; Zan, K; Cui, G; Ye, X

    2016-06-01

    High-mobility group box 1 (HMGB1), a ligand of receptor for advanced glycation endproducts (RAGE), functions as a proinflammatory factor. It is mainly involved in inflammatory activation and contributes to the initiation and progression of stroke. By using a model of transient middle cerebral artery occlusion (MCAo) in type 2 diabetic rats, we investigated the changes of pro-inflammation mediators, blood-brain barrier (BBB) leakage and functional outcome after stroke. Type 2 diabetic rats did not show an increased lesion volume, but exhibited significantly increased expression of HMGB1 and RAGE, BBB leakage, as well as decreased functional outcome after stroke compared with control rats. Injection of bone marrow stromal cells (BMSCs) into type 2 diabetic rats significantly reduced the expression of HMGB1 and RAGE, attenuated BBB leakage, and improved functional outcome after stroke. BMSCs-treated type 2 diabetic rats inhibited inflammation and improved functional outcome after stroke. Furthermore, in vitro data support the hypothesis that BMSCs-induced reduction of HMGB1 and RAGE in T2DM-MCAo rats contributed to attenuated inflammatory response in the ischemic brain, which may lead to the beneficial effects of BMSCs treatment. Further investigation of BMSCs treatment in type 2 diabetic stroke is warranted. PMID:26946264

  7. High b value DWI in evaluation of the hyperacute cerebral ischemia at 3T: A comparative study in an embolic canine stroke model

    PubMed Central

    Cheng, Qiguang; Xu, Xiaoquan; Zu, Qingquan; Lu, Shanshan; Yu, Jing; Liu, Xinglong; Wang, Bin; Shi, Haibin; Teng, Gaojun; Liu, Sheng

    2016-01-01

    Previous studies have indicated that the temporal change of relative diffusion weighted imaging (rDWI) signal intensity may help to determine the onset time of a stroke. Furthermore, several studies have indicated that high b value DWI offered improved detection rates for hyper-acute ischemic lesions compared with standard b value DWI. However, the temporal changes of the rDWI on high b value DWI remain unclear. Therefore, based on our embolic canine stroke model, we evaluated the temporal evolution of rDWI on high b value DWI, and further compared its diagnostic value in predicting the onset time of ischemic stroke with rDWI on standard b value DWI. Twelve canine MCAO models were established, and DWI was performed at 1, 2, 3, 4, 5 and 6 h after MCAO, with 3 b values of 1,000, 2,000 and 3,000. High b value DWI detected all ischemic lesions after 1 h, while standard b value did not detect the ischemic lesions in one dog at 1 h. With all three of the tested b values, rDWIs increased continuously within 6 h, while relative apparent diffusion coefficient (rADC) values rapidly decreased in 1 h, then became relatively stable. The area under the curve values for rDWI with b value of 1,000, 2,000 and 3,000, in predicting ischemic lesions within 3 h were 0.897, 0.929 and 0.938, while for rADC were 0.645, 0.583 and 0.599, respectively. Therefore, the results indicated that the rDWI was helpful in aging hyper-acute ischemic stroke, while rADC appeared not to be. High b value DWI had a higher detection rate for ischemic lesions and better predictive efficacy in determining the onset time of hyper-acute stroke. PMID:27446301

  8. Post-Operative Multiple Thrombosis Associated with Patent Foramen Ovale: Embolic Stroke, Right Atrial Thrombi, Pulmonary Embolism and Deep Vein Thrombosis

    PubMed Central

    Cho, Sun-Young; Park, Mi-Youn; Shim, Byung-Ju; Lee, Seung-Jae; Kim, Jeong-Ho; Park, Jung-Ku; Oh, Chang-Yul; Ahn, So-Hyun; Cho, Woo-Hyun

    2015-01-01

    Patients undergoing total joint arthroplasty frequently develop post-operative complication, such as deep vein thrombosis and pulmonary thromboembolism. However, it is not common coexisting deep vein thrombosis, pulmonary thromboembolisms, right atrial thrombus and acute cerebral infarction raised by thrombus through patent foramen ovale. We reported the patient who had multiple thrombi which were accompanied with a cryptogenic ischemic stroke and associated with patent foramen ovale after operation. PMID:26448826

  9. Dodecafluoropentane Emulsion (DDFPe) Decreases Stroke Size and Improves Neurological Scores in a Permanent Occlusion Rat Stroke Model

    PubMed Central

    Brown, A.T; Arthur, M.C; Nix, J.S; Montgomery, J.A; Skinner, R.D; Roberson, P.K; Borrelli, Michael; Culp, W.C

    2014-01-01

    Background: Dodecafluoropentane emulsion (DDFPe), given IV one hour after stroke, has been shown to greatly reduce the percent stroke volume (%SV) in rabbits. With repeated doses its effect continued for 24 hours. Purpose: Test DDFPe as neuroprotective agent in permanent occlusion rat stroke models in Sprague Dawley (SD) and Spontaneously Hypertensive Rats (SHR) measuring both %SV and neurological assessment scores (NAS). Methods: The male rats received either saline (control), or one or four doses (1x or 4x) of DDFPe (0.6ml/kg IV) one hour post stroke. Treatment groups were SD (n=26) (control, 1x and 4x; n=12, 7 and 7) and SHR (n=14) (control, 1x and 4x; n=7, 3 and 4). The 4x doses were given at 1.5 hour intervals. At six hours post stroke, the rats received a NAS using standard tests for balance, reflexes, and motor performance. Then rats were euthanized and brains removed for TTC evaluation of %SV. Results: For %SV analysis strain differences were not significant therefore strains were combined. DDFPe significantly decreased %SV in 1x and 4xDDFPe groups compared to control groups (2.59±1.81 and 0.98±0.88 vs. 9.24±6.06, p≤0.001 each; p≤0.0001 for the overall test for treatment effect). The 1x versus 4xDDFPe groups were not significantly different (p=0.40). In NAS analysis both strains showed significant improvement with 4xDDFPe therapy vs. controls, (SD: 5.00+2.45 vs. 9.36+3.56, p=0.01; SHR: 7.75+4.43 vs. 12.14+3.08, p=0.05). Differences between the 1x DDFPe group and controls were not significant (SD: 8.43+3.69; SHR: 9. 33+3.51). Conclusion: DDFPe treatment provides significant neuroprotection when assessed six hours post stroke. PMID:25674164

  10. Improved Therapeutic Benefits by Combining Physical Cooling With Pharmacological Hypothermia After Severe Stroke in Rats

    PubMed Central

    Lee, Jin Hwan; Wei, Ling; Gu, Xiaohuan; Won, Soonmi; Wei, Zheng Zachory; Dix, Thomas A.

    2016-01-01

    Background and Purpose— Therapeutic hypothermia is a promising strategy for treatment of acute stroke. Clinical translation of therapeutic hypothermia, however, has been hindered because of the lack of efficiency and adverse effects. We sought to enhance the clinical potential of therapeutic hypothermia by combining physical cooling (PC) with pharmacologically induced hypothermia after ischemic stroke. Methods— Wistar rats were subjected to 90-minute middle cerebral artery occlusion by insertion of an intraluminal filament. Mild-to-moderate hypothermia was induced 120 minutes after the onset of stroke by PC alone, a neurotensin receptor 1 (NTR1) agonist HPI-201 (formally ABS-201) alone or the combination of both. The outcomes of stroke were evaluated at 3 and 21 days after stroke. Results— PC or HPI-201 each showed hypothermic effect and neuroprotection in stroke rats. The combination of PC and HPI-201 exhibited synergistic effects in cooling process, reduced infarct formation, cell death, and blood-brain barrier damages and improved functional recovery after stroke. Importantly, coapplied HPI-201 completely inhibited PC-associated shivering and tachycardia. Conclusions— The centrally acting hypothermic drug HPI-201 greatly enhanced the efficiency and efficacy of conventional PC; this combined cooling therapy may facilitate clinical translation of hypothermic treatment for stroke. PMID:27301934

  11. Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke

    PubMed Central

    2013-01-01

    Background The human population mostly affected by stroke is more than 65 years old. This study was designed to meet the recommendation that models of cerebral ischemia in aged animals are more relevant to the clinical setting than young animal models. Until now the majority of the pre-clinical studies examining age effects on stroke outcomes have used rats of old age. Considering the increasing incidence of stroke among younger than old human population, new translational approaches in animal models are needed to match the rejuvenation of stroke. A better knowledge of alterations in stroke outcomes in middle-aged rats has important preventive and management implications providing clues for future investigations on effects of various neuroprotective and neurorestorative drugs against cerebrovascular accidents that may occur before late senescence. Methods We evaluated the impact of transient focal ischemia, induced by intracerebral unilateral infusion of endothelin-1 (Et-1) near the middle cerebral artery of conscious rats, on volume of brain damage and asymmetry in behavioral and electroencephalographic (EEG) output measures in middle-aged (11–12 month-old) rats. Results We did not find any age-dependent difference in the volume of ischemic brain damage three days after Et-1 infusion. However, age was an important determinant of neurological and EEG outcomes after stroke. Middle-aged ischemic rats had more impaired somatosensory functions of the contralateral part of the body than young ischemic rats and thus, had greater left-right reflex/sensorimotor asymmetry. Interhemispheric EEG asymmetry was more evident in middle-aged than in young ischemic rats, and this could tentatively explain the behavioral asymmetry. Conclusions With a multiparametric approach, we have validated the endothelin model of ischemia in middle-aged rats. The results provide clues for future studies on mechanisms underlying plasticity after brain damage and motivate investigations of

  12. Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats

    PubMed Central

    Su, Qiaoer; Cheng, Yifan; Jin, Kunlin; Cheng, Jianhua; Lin, Yuanshao; Lin, Zhenzhen; Wang, Liuqing; Shao, Bei

    2016-01-01

    The present study investigated the effect of exogenous estrogen on post-stroke depression. Rats were exposed to chronic mild stress following middle cerebral artery occlusion. The occurrence of post-stroke depression was evaluated according to the changes in preference for sucrose and performance in a forced swimming test. Estrogen therapy significantly improved these neurological symptoms, indicating that estrogen is effective in treating post-stroke depression. Increased brain-derived neurotrophic factor (BDNF) expression was reported in the hippocampus of rats that had been treated with estrogen for two weeks, suggesting that BDNF expression may be an important contributor to the improvement of post-stroke depression that is observed following estrogen therapy. PMID:27602095

  13. Cardiovascular Deconditioning and Venous Air Embolism in Simulated Microgravity in the Rat

    NASA Technical Reports Server (NTRS)

    Robinson, R. R.; Doursout, M.-F.; Chelly, J. E.; Powell, M. R.; Little, T. M.; Butler,B. D.

    1996-01-01

    Astronauts conducting extravehicular activities undergo decompression to a lower ambient pressure, potentially resulting in gas bubble formation within the tissues and venous circulation. Additionally, exposure to microgravity produces fluid shifts within the body leading to cardiovascular deconditioning. A lower incidence of decompression illness in actual spaceflight compared with that in ground-based altitude chamber flights suggests that there is a possible interaction between microgravity exposure and decompression illness. The purpose of this study was to evaluate the cardiovascular and pulmonary effects of simulated hypobaric decompression stress using a tail suspension (head-down tilt) model of microgravity to produce the fluid shifts associated with weightlessness in conscious, chronically instrumented rats. Venous bubble formation resulting from altitude decompression illness was simulated by a 3-h intravenous air infusion. Cardiovascular deconditioning was simulated by 96 h of head-down tilt. Heart rate, mean arterial blood pressure, central venous pressure, left ventricular wall thickening and cardiac output were continuously recorded. Lung studies were performed to evaluate edema formation and compliance measurement. Blood and pleural fluid were examined for changes in white cell counts and protein concentration. Our data demonstrated that in tail-suspended rats subjected to venous air infusions, there was a reduction in pulmonary edema formation and less of a decrease in cardiac output than occurred following venous air infusion alone. Mean arterial blood pressure and myocardial wall thickening fractions were unchanged with either tail-suspension or venous air infusion. Heart rate decreased in both conditions while systemic vascular resistance increased. These differences may be due in part to a change or redistribution of pulmonary blood flow or to a diminished cellular response to the microvascular insult of the venous air embolization.

  14. Delayed treatment with chondroitinase ABC promotes sensorimotor recovery and plasticity after stroke in aged rats.

    PubMed

    Soleman, Sara; Yip, Ping K; Duricki, Denise A; Moon, Lawrence D F

    2012-04-01

    Stroke is the dominant cause of sensorimotor disability that primarily affects the elderly. We now show that neuroplasticity and functional recovery after stroke is constrained by inhibitory chondroitin sulphates. In two blinded, randomized preclinical trials, degradation of chondroitin sulphate using chondroitinase ABC reactivated neuroplasticity and promoted sensorimotor recovery after stroke in elderly rats. Three days after stroke, chondroitinase ABC was microinjected into the cervical spinal cord to induce localized plasticity of forelimb sensorimotor spinal circuitry. Chondroitinase ABC effectively removed chondroitin sulphate from the extracellular matrix and perineuronal nets. Three different tests of sensorimotor function showed that chondroitinase ABC promoted recovery of forelimb function. Anterograde and retrograde tracing showed that chondroitinase ABC also induced sprouting of the contralesional corticospinal tract in the aged treated hemicord. Chondroitinase ABC did not neuroprotect the peri-infarct region. We show for the first time delayed chondroitinase ABC treatment promotes neuroanatomical and functional recovery after focal ischaemic stroke in an elderly nervous system. PMID:22396394

  15. Spontaneously hypertensive rats display reduced microglial activation in response to ischemic stroke and lipopolysaccharide

    PubMed Central

    2012-01-01

    Background For successful translation to clinical stroke studies, the Stroke Therapy Academic Industry Round Table criteria have been proposed. Two important criteria are testing of therapeutic interventions in conscious animals and the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke and influences the clinical outcome. We aimed to compare the susceptibility to ischemia in hypertensive rats with those in normotensive controls in a rat model for induction of ischemic stroke in conscious animals. Methods The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs) to induce a transient decrease in striatal blood flow, which was measured by the Laser Doppler technique. Infarct size was assessed histologically by Cresyl Violet staining. Sensory-motor functions were measured at several time points using the Neurological Deficit Score. Activation of microglia and astrocytes in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68/Iba-1 and glial fibrillary acidic protein. Results and conclusions The SHRs showed significantly larger infarct volumes and more pronounced sensory-motor deficits, compared to the WKYRs at 24 h after the insult. However, both differences disappeared between 24 and 72 h. In SHRs, microglia were less susceptible to activation by lipopolysaccharide and there was a reduced microglial activation after induction of ischemic stroke. These quantitative and qualitative differences may be relevant for studying the efficacy of new treatments for stroke in accordance to the Stroke Therapy Academic Industry Round Table criteria. PMID:22647642

  16. OBESITY INCREASES BLOOD PRESSURE, CEREBRAL VASCULAR REMODELING, AND SEVERITY OF STROKE IN THE ZUCKER RAT

    PubMed Central

    Osmond, Jessica M.; Mintz, James D.; Dalton, Brian; Stepp, David W.

    2009-01-01

    Obesity is a risk factor for stroke, but the mechanisms by which obesity increases stroke risk are unknown. Because microvascular architecture contributes to the outcome of stroke, we hypothesized that middle cerebral arteries (MCA) from obese Zucker rats (OZR) undergo inward remodeling and develop increased myogenic tone compared to lean Zucker rats (LZR). We further hypothesized that OZR have an increased infarct following cerebral ischemia and that changes in vascular structure and function correlate with the development of hypertension in OZR. Blood pressure was measured by telemetery in LZR and OZR from 6 to 17 weeks of age. Vessel structure and function were assessed in isolated MCAs. Stroke damage was assessed after ischemia was induced for 60 minutes followed by 24 hours of reperfusion. While mean arterial pressure (MAP) was similar between young rats (6–8 weeks old), MAP was higher in adult (14–17 weeks old) OZR than LZR. MCAs from OZR had a smaller lumen diameter and increased myogenic vasoconstriction compared to those from LZR. Following ischemia, infarction was 58% larger in OZR than LZR. Prior to the development of hypertension, MCA myogenic reactity and lumen diameter as well as infarct size were similar between young LZR and OZR. Our results indicate that the MCAs of OZR undergo structural remodeling and that these rats have greater cerebral injury following cerebral ischemia. These cerebrovascular changes correlate with the development of hypertension and suggest that the increased blood pressure may be the major determinant for stroke risk in obese individuals. PMID:19104000

  17. The genomic response of the ipsilateral and contralateral cortex to stroke in aged rats

    PubMed Central

    Buga, A-M; Sascau, M; Pisoschi, C; Herndon, J G; Kessler, C; Popa-Wagner, A

    2008-01-01

    Aged rats recover poorly after unilateral stroke, whereas young rats recover readily possibly with the help from the contralateral, healthy hemisphere. In this study we asked whether anomalous, age-related changes in the transcriptional activity in the brains of aged rats could be one underlying factor contributing to reduced functional recovery. We analysed gene expression in the periinfarct and contralateral areas of 3-month- and 18-month-old Sprague Dawley rats. Our experimental end-points were cDNA arrays containing genes related to hypoxia signalling, DNA damage and apoptosis, cellular response to injury, axonal damage and re-growth, cell lineage differentiation, dendritogenesis and neurogenesis. The major transcriptional events observed were: (i) Early up-regulation of DNA damage and down-regulation of anti-apoptosis-related genes in the periinfarct region of aged rats after stroke; (ii) Impaired neurogenesis in the periinfarct area, especially in aged rats; (iii) Impaired neurogenesis in the contralateral (unlesioned) hemisphere of both young and aged rats at all times after stroke and (iv) Marked up-regulation, in aged rats, of genes associated with inflammation and scar formation. These results were confirmed with quantitative real-time PCR. We conclude that reduced transcriptional activity in the healthy, contralateral hemisphere of aged rats in conjunction with an early up-regulation of DNA damage-related genes and pro-apoptotic genes and down-regulation of axono- and neurogenesis in the periinfarct area are likely to account for poor neurorehabilitation after stroke in old rats. PMID:18266980

  18. Detection of occult atrial fibrillation in patients with embolic stroke of uncertain source: a work in progress

    PubMed Central

    Andrade, Jason G.; Field, Thalia; Khairy, Paul

    2015-01-01

    Atrial fibrillation accounts for a substantial proportion of ischemic strokes of known etiology and may be responsible for an additional subset of the 25–40% of strokes of unknown cause (so-called cryptogenic). Oral anticoagulation is significantly more effective than antiplatelet therapy in the secondary prevention of atrial fibrillation-related strokes, providing justification for developing more sensitive approaches to detecting occult paroxysms of atrial fibrillation. In this article, we summarize the current state of knowledge regarding the value of in-hospital and out-patient monitoring for detecting atrial fibrillation in the context of cryptogenic stroke. We review the evidence for and against screening with standard Holter monitors, external loop recorders, the newer real-time continuous attended cardiac monitoring systems, cardiac implantable electronic devices, and insertable loop recorders. We review key questions regarding prolonged cardiac arrhythmia monitoring, including the relationship between duration of the atrial fibrillation episode and risk of thromboembolism, frequency of monitoring and its impact on the diagnostic yield in detecting occult or subclinical atrial fibrillation, and the temporal proximity of device-detected atrial fibrillation to stroke events. We conclude by proposing avenues for further research. PMID:25883570

  19. CCD-camera-based diffuse optical tomography to study ischemic stroke in preclinical rat models

    NASA Astrophysics Data System (ADS)

    Lin, Zi-Jing; Niu, Haijing; Liu, Yueming; Su, Jianzhong; Liu, Hanli

    2011-02-01

    Stroke, due to ischemia or hemorrhage, is the neurological deficit of cerebrovasculature and is the third leading cause of death in the United States. More than 80 percent of stroke patients are ischemic stroke due to blockage of artery in the brain by thrombosis or arterial embolism. Hence, development of an imaging technique to image or monitor the cerebral ischemia and effect of anti-stoke therapy is more than necessary. Near infrared (NIR) optical tomographic technique has a great potential to be utilized as a non-invasive image tool (due to its low cost and portability) to image the embedded abnormal tissue, such as a dysfunctional area caused by ischemia. Moreover, NIR tomographic techniques have been successively demonstrated in the studies of cerebro-vascular hemodynamics and brain injury. As compared to a fiberbased diffuse optical tomographic system, a CCD-camera-based system is more suitable for pre-clinical animal studies due to its simpler setup and lower cost. In this study, we have utilized the CCD-camera-based technique to image the embedded inclusions based on tissue-phantom experimental data. Then, we are able to obtain good reconstructed images by two recently developed algorithms: (1) depth compensation algorithm (DCA) and (2) globally convergent method (GCM). In this study, we will demonstrate the volumetric tomographic reconstructed results taken from tissuephantom; the latter has a great potential to determine and monitor the effect of anti-stroke therapies.

  20. Neurorestorative Therapy of Stroke in Type two Diabetes Rats Treated with Human Umbilical Cord Blood Cells

    PubMed Central

    Yan, Tao; Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Ning, Ruizhuo; Cui, Yisheng; Roberts, Cynthia; Kuzmin-Nichols, Nicole; Sanberg, Cyndy Davis; Chen, Jieli

    2015-01-01

    Background and Purpose Diabetes mellitus is a high risk factor for ischemic stroke. Diabetic stroke patients suffer worse outcomes, poor long term recovery, risk of recurrent strokes and extensive vascular damage. We investigated the neurorestorative effects and the underlying mechanisms of stroke treatment with human umbilical cord blood cells (HUCBCs) in Type two diabetes mellitus (T2DM) rats. Methods Adult male T2DM rats were subjected to 2 h of middle cerebral artery occlusion (MCAo). Three days after MCAo, rats were treated via tail-vein injection with: 1) phosphate-buffered-saline (PBS); 2) HUCBCs (5×106); n=10/group. Results HUCBC stroke treatment initiated 3 days after MCAo in T2DM rats did not significantly decrease blood-brain-barrier (BBB) leakage (p=0.1) and lesion volume (p=0.078), but significantly improved long term functional outcome and decreased brain hemorrhage (p<0.05) when compared to the PBS-treated T2DM-MCAo control group. HUCBC treatment significantly promoted white matter (WM) remodeling as indicated by increased expression of Bielschowsky silver (axons marker), Luxol fast blue (myelin marker), SMI-31 (neurofilament) and Synaptophysin in the ischemic border zone (IBZ). HUCBC promoted vascular remodeling, and significantly increased arterial and vascular density. HUCBC treatment of stroke in T2DM rats significantly increased M2 macrophage polarization (increased M2 macrophage CD163, CD 206; decreased M1 macrophage ED1 and iNOS expression) in the ischemic brain compared to PBS-treated T2DM-MCAo controls (p<0.05). HUCBC also significantly decreased pro-inflammatory factors i.e., matrix metalloproteinase 9 (MMP9), receptor for advanced glycation end-products (RAGE) and toll like receptor 4 (TLR4) expression in the ischemic brain. Conclusion HUCBC treatment initiated 3 days after stroke significantly increased WM and vascular remodeling in the ischemic brain as well as decreased neuroinflammatory factor expression in the ischemic brain in T2DM

  1. Local Administration of AAV-BDNF to Subventricular Zone Induces Functional Recovery in Stroke Rats

    PubMed Central

    Yu, Seong-Jin; Tseng, Kuan-Yin; Shen, Hui; Harvey, Brandon K.; Airavaara, Mikko; Wang, Yun

    2013-01-01

    Migration of new neuroprogenitor cells (NPCs) from the subventricular zone (SVZ) plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF) enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV‐BDNF infection was verified in primary neuronal culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats at 14 days prior to right middle cerebral artery occlusion (MCAo). SVZ tissues were collected from the brain and placed in Metrigel cultures 1 day after MCAo. Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local administration of AAV-BDNF significantly enhanced recovery of locomotor function and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ increases behavioral recovery post stroke, possibly through the enhancement of migration of cells from SVZ in stroke animals. Regional manipulation of BDNF expression through AAV may be a novel approach for neurorepair in stroke brains. PMID:24312581

  2. Cardiac inflammation contributes to right ventricular dysfunction following experimental pulmonary embolism in rats.

    PubMed

    Watts, John A; Zagorski, John; Gellar, Michael A; Stevinson, Brad G; Kline, Jeffrey A

    2006-08-01

    Acute right ventricular (RV) failure following pulmonary embolism (PE) is a strong predictor of poor clinical outcome. Present studies test for an association between RV failure from experimental PE, inflammation, and upregulated chemokine expression. Additional experiments test if neutrophil influx contributes to RV dysfunction. PE was induced in male rats by infusing 24 microm microspheres (right jugular vein) producing mild hypertension (1.3 million beads/100 g, PE1.3), or moderately severe hypertension (2.0 million beads/100 g, PE2.0). Additional rats served as vehicle sham (0.01% Tween 20, Veh). In vivo RV peak systolic pressures (RVPSP) increased significantly, and then declined following PE2.0 (51 +/- 1 mm Hg 2 h; 49 +/- 1, 6 h; 44 +/- 1, 18 h). RV generated pressure of isolated, perfused hearts was significantly reduced in PE2.0 compared with PE1.3 or Veh. MCP-1 protein (ELISA) was elevated 21-fold and myeloperoxidase activity 95-fold in RV of PE2.0 compared with Veh or PE1.3. CINC-1, CINC-2, MIP-2, MCP-1, and MIP-1alpha mRNA also increased in RV of PE2.0. Histological analysis revealed massive accumulation of neutrophils (selective esterase stain) and monocyte/macrophages (CD68, ED-1) in RV of PE2.0 hearts in regions of myocyte damage. Electron microscopy showed myocyte necrosis and phagocytosis by inflammatory cells. LV function was normal and did not show increased inflammation after PE2.0. Treatment with anti-PMN antibody reduced RV MPO activity and prevented RV dysfunction. Conclusions-PE with moderately severe pulmonary hypertension (PE2.0) resulted in selective RV dysfunction, which was associated with increased chemokine expression, and infiltration of both neutrophils and monocyte/macrophages, indicating that a robust immune response occurred with RV damage following experimental PE. Experimental agranulocytosis reduced RV, suggesting that neutrophil influx contributed to RV damage. PMID:16814320

  3. Pre-ischemic exercise alleviates oxidative damage following ischemic stroke in rats.

    PubMed

    Feng, Rui; Zhang, Min; Wang, Xiao; Li, Wen-Bin; Ren, Shi-Qing; Zhang, Feng

    2014-10-01

    Physical exercise has been proved to be neuroprotective in clinical trials and animal experiments. However, the exact mechanism underlying this neuroprotective effect remains unclear. The aim of the present study was to explore whether pre-ischemic treadmill training could act as a form of ischemic preconditioning in a rat following ischemic stroke by reducing oxidative damage. Fifty-four rats were randomly divided into three groups (n=18 per group): Sham surgery, middle cerebral artery occlusion (MCAO) without exercise and MCAO with exercise. Subsequent to treadmill training, ischemic stroke was induced by occluding the MCA for 1.5 h, followed by reperfusion. Six rats in each group were evaluated for neurological deficits and then sacrificed by decapitation to calculate the infarct volume. The remaining rats in each group were sacrificed to detect the level of superoxide dismutase (SOD) activity (n=6) and malondialdehyde (MDA) concentration (n=6). The results indicated that pre-ischemic exercise training reduced brain infarct volume and neurological deficits, increased SOD activity and decreased the concentration of MDA following ischemic stroke. In conclusion, treadmill exercise training prior to MCAO/reperfusion increased the antioxidant ability and decreased the oxidative damage in the brain subsequent to ischemic stroke. PMID:25187848

  4. Systemic air embolism causing acute stroke and myocardial infarction after percutaneous transthoracic lung biopsy - a case report.

    PubMed

    Rehwald, Rafael; Loizides, Alexander; Wiedermann, Franz J; Grams, Astrid E; Djurdjevic, Tanja; Glodny, Bernhard

    2016-01-01

    The air embolism in this case was likely to have been caused by positioning the patient in a prone position, which was associated with the lesion to be biopsied being at a maximum height over the left atrium. Due to the resulting negative pressure, air entered through a fistula that formed between the airspace and the pulmonary vein. The air could have been trapped in the left atrium by positioning the patient in left lateral position. The event itself could have been prevented by positioning the patient in an ipsilateral dependent position during the biopsy. In addition to hyperbaric oxygen therapy, the preferred treatment options are positioning maneuvers, administration of pure oxygen, and heparinization. PMID:27154545

  5. Endovascular embolization

    MedlinePlus

    Treatment - endovascular embolism; Coil embolization; Cerebral aneurysm - endovascular; Coiling - endovascular; Saccular aneurysm - endovascular; Berry aneurysm - endovascular repair; Fusiform aneurysm repair - endovascular; Aneurysm repair - endovascular

  6. In vivo bioimpedance changes during haemorrhagic and ischaemic stroke in rats: towards 3D stroke imaging using electrical impedance tomography.

    PubMed

    Dowrick, T; Blochet, C; Holder, D

    2016-06-01

    Electrical impedance tomography (EIT) could be used as a portable non-invasive means to image the development of ischaemic stroke or haemorrhage. The purpose of this study was to examine if this was possible using time difference imaging, in the anesthetised rat using 40 spring-loaded scalp electrodes with applied constant currents of 50-150 μA at 2 kHz. Impedance changes in the largest 10% of electrode combinations were  -12.8%  ±  12.0% over the first 10 min for haemorrhage and  +46.1%  ±  37.2% over one hour for ischaemic stroke (mean  ±  SD, n  =  7 in each group). The volume of the pathologies, assessed by tissue section and histology post-mortem, was 12.6 μl  ±  17.6 μl and 12.6 μl  ±  17.6 μl for haemorrhage and ischaemia respectively. In time difference EIT images, there was a correspondence with the pathology in 3/7 cases of haemorrhage and none of the ischaemic strokes. Although the net impedance changes were physiologically reasonable and consistent with expectations from the literature, it was disappointing that it was not possible to obtain reliable EIT images. The reason for this are not clear, but probably include confounding effects of secondary ischaemia for haemorrhage and tissue and cerebrospinal fluid shifts for the stroke model. With this method, it does not appear that EIT with scalp electrodes is yet ready for clinical use. PMID:27200510

  7. Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats.

    PubMed

    Chao, Xiaodong; Zhou, Jun; Chen, Tao; Liu, Wenbo; Dong, Wenpeng; Qu, Yan; Jiang, Xiaofan; Ji, Xituan; Zhen, Haining; Fei, Zhou

    2010-12-01

    Osthole, a natural coumarin derivative, has taken considerable attention because of its diverse pharmacological functions. It has been reported to be useful in the treatment of chronic cerebral hypoperfusion and neuronal damage. In the present study, we examined the neuroprotective effect of osthole and its potential mechanisms against acute ischemic stroke induced by middle cerebral artery occlusion (MCAO) in rats. The rats were pretreated with osthole 10, 20 and 40 mg/kg 30 min before MCAO. The neuroprotective effect of osthole against acute ischemic stroke was evaluated by neurological deficit score (NDS), dry-wet weight and 2,3,5-triphenyltetrazolium chloride (TTC) staining. The contents of malondialdehyde (MDA) and glutathione (GSH), activity of myeloperoxidase (MPO) and the level of interleukin (IL)-1β and IL-8 after 2h of MCAO in rats were detected to investigate its anti-oxidative action and anti-inflammatory property. Pretreatment with osthole significantly increased in GSH, and decreased the volume of infarction, NDS, edema, MDA, MPO, IL-1β and IL-8 compared with rats in the MCAO group at 24h after MCAO. The study suggests the neuroprotective effect of osthole in the MCAO model of rats. The anti-oxidative action and anti-inflammatory property of osthole may contribute to a beneficial effect against stroke. PMID:20869955

  8. Blocking Sympathetic Nervous System Reverses Partially Stroke-Induced Immunosuppression but does not Aggravate Functional Outcome After Experimental Stroke in Rats.

    PubMed

    Deng, Qi-Wen; Yang, Heng; Yan, Fu-Ling; Wang, Huan; Xing, Fang-Lan; Zuo, Lei; Zhang, Han-Qing

    2016-08-01

    Stoke results in activation of the sympathetic nervous system (SNS), inducing systemic immunosuppression. However, the potential mechanisms underlying stroke-induced immunosuppression remain unclear. Here, we determined the SNS effects on functional outcome and explored the interactions among SNS, β-arrestin2 and nuclear factor-κB (NF-κB) after experimental stroke in rats. In the current study, stroke was induced by a transient middle cerebral artery occlusion (MCAO) in rats, and SNS activity was inhibited by intraperitoneal injection of 6-hydroxydopamine HBr (6-OHDA). 7.0 T Micro-MRI and Longa score were employed to assess the functional outcome after stroke. Flow cytometry and ELISA assay were used to measure the expression of MHC class II, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Western blot was conducted to analyze β-arrestin2 and NF-κB protein expression levels after experimental stroke. We found significantly increased infarct volumes and functional impairment after MCAO at different post-surgery time points, which were not aggravated by 6-OHDA treatment. SNS blockade partially reversed the expression of MHC class II after stroke over time, as well as TNF-α and IFN-γ levels in lipopolysaccharide-stimulated macrophages in vitro. Treatment of MCAO rats with SNS-inhibitor significantly diminished NF-κB activation and enhanced β-arrestin2 expression after stroke. This study suggests that pharmacological SNS inhibition dose not aggravate functional outcome after stroke. Stroke-induced immunosuppression may be involved in the SNS-β-arrestin2-NF-κB pathway. PMID:27059792

  9. Constraint-induced movement therapy enhanced neurogenesis and behavioral recovery after stroke in adult rats.

    PubMed

    Zhao, Chuansheng; Wang, Jun; Zhao, Shanshan; Nie, Yingxue

    2009-08-01

    Constraint-induced movement therapy (CIMT) has been extensively used for stroke rehabilitation. CIMT encourages use of the impaired limb along with restraint of the ipsilesional limb in daily life, and may promote behavioral recovery and induce structural changes in brain after stroke. The aim of this study was to investigate whether CIMT enhances neurogenesis in rat brain after stroke that was generated by middle cerebral artery occlusion. Adult rats were divided into sham group, ischemia group and ischemia treated with CIMT group. Rats of CIMT group were treated with a plaster cast to restrain the healthy forelimb for 14 days beginning 1 week after ischemia. The proliferation of neuronal cells labeled with bromodeoxyuridine (BrdU) and behavioral recovery were analyzed at day 29 after ischemia. We also measured the tissue level of stromal cell-derived factor 1 (SDF-1) by ELISA. SDF-1 might be involved in the regulation of neurogenesis following stroke. In the subventricular zone of the animals treated with CIMT, there was a significant increase in the number of BrdU-positive cells (135 +/- 18, P < 0.05), compared with ischemia group (87 +/- 12) or sham group (18 +/- 3.6). Likewise, in the dentate gyrus, animals treated with CIMT showed a significant increase in BrdU-positive cells (296 +/- 26, P < 0.05) compared with ischemia group (225 +/- 18) or sham group (162 +/- 11). CIMT treatment after stroke significantly improved behavioral performances and increased the SDF-1 protein levels in the cortex and dentate gyrus. In conclusion, CIMT treatment enhances neurogenesis and functional recovery after stroke. PMID:19638734

  10. Progesterone improves long-term functional and histological outcomes after permanent stroke in older rats.

    PubMed

    Wali, Bushra; Ishrat, Tauheed; Stein, Donald G; Sayeed, Iqbal

    2016-05-15

    Previous studies have shown progesterone to be beneficial in animal models of central nervous system injury, but less is known about its longer-term sustained effects on recovery of function following stroke. We evaluated progesterone's effects on a panel of behavioral tests up to 8 weeks after permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley rats 12m.o. were subjected to pMCAO and, beginning 3h post-pMCAO, given intraperitoneal injections of progesterone (8mg/kg) or vehicle, followed by subcutaneous injections at 8h and then every 24h for 7 days, with tapering of the last 2 treatments. The rats were then tested on functional recovery at 3, 6 and 8 weeks post-stroke. We observed that progesterone-treated animals showed attenuation of infarct volume and improved functional outcomes at 8 weeks after stroke on grip strength, sensory neglect, motor coordination and spatial navigation tests. Progesterone treatments significantly improved motor deficits in the affected limb on a number of gait parameters. Glial fibrillary acidic protein expression was increased in the vehicle group and considerably lowered in the progesterone group at 8 weeks post-stroke. With repeated post-stroke testing, sensory neglect and some aspects of spatial learning performance showed spontaneous recovery, but on gait and grip-strength measres progesterone given only in the acute stage of stroke (first 7 days) showed sustained beneficial effects on all other measures of functional recovery up to 8 weeks post-stroke. PMID:26921692

  11. Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats.

    PubMed

    Levijoki, Jouko; Kivikko, Matti; Pollesello, Piero; Sallinen, Jukka; Hyttilä-Hopponen, Minja; Kuoppamäki, Mikko; Haasio, Kristiina; Gröhn, Olli; Miettinen, Riitta; Puoliväli, Jukka; Tähtivaara, Leena; Yrjänheikki, Juha; Haapalinna, Antti

    2015-03-01

    The effects of levosimendan on cerebrovascular lesions and mortality were investigated in models of primary and secondary stroke. We aimed to determine whether the effects of levosimendan are comparable to and/or cumulative with those of valsartan, and to investigate whether levosimendan-induced vasodilation has a role in its effects on stroke. In a primary stroke Dahl/Rapp rat model, mortality rates were 70% and 5% for vehicle and levosimendan, respectively. Both stroke incidence (85% vs. 10%, P<0.001) and stroke-associated behavioral deficits (7-point neuroscore: 4.59 vs. 5.96, P<0.001) were worse for vehicle compared to levosimendan. In a secondary stroke model in which levosimendan treatment was started after cerebrovascular incidences were already detected, mean survival times were 15 days with vehicle, 20 days with levosimendan (P=0.025, vs. vehicle), 22 days with valsartan (P=0.001, vs. vehicle), and 31 days with levosimendan plus valsartan (P<0.001, vs. vehicle). The respective survivals were 0%, 16%, 20% and 59%, and the respective incidences of severe lesions were 50%, 67%, 50% and 11%. In this rat model, levosimendan increased blood volume of the cerebral vessels, with significant effects in the microvessels of the cortex (∆R=3.5±0.15 vs. 2.7±0.17ml for vehicle; P=0.001) and hemisphere (∆R=3.2±0.23 vs. 2.6±0.14ml for vehicle; P=0.018). Overall, levosimendan significantly reduced stroke-induced mortality and morbidity, both alone and with valsartan, with apparent cumulative effects, an activity in which the vasodilatory effects of levosimendan have a role. PMID:25641751

  12. Spatio-temporal course of macrophage-like cell accumulation after experimental embolic stroke depending on treatment with tissue plasminogen activator and its combination with hyperbaric oxygenation

    PubMed Central

    Michalski, D.; Heindl, M.; Kacza, J.; Laignel, F.; Küppers-Tiedt, L.; Schneider, D.; Grosche, J.; Boltze, J.; Löhr, M.; Hobohm, C.; Härtig, W.

    2012-01-01

    Inflammation following ischaemic stroke attracts high priority in current research, particularly using human-like models and long-term observation periods considering translational aspects. The present study aimed on the spatio-temporal course of macrophage-like cell accumulation after experimental thromboembolic stroke and addressed microglial and astroglial reactions in the ischaemic border zone. Further, effects of tissue plasminogen activator (tPA) as currently best treatment for stroke and the potentially neuroprotective co-administration of hyperbaric oxygen (HBO) were investigated. Rats underwent middle cerebral artery occlusion and were assigned to control, tPA or tPA+HBO. Twenty-four hours, 7, 14 and 28 days were determined as observation time points. The accumulation of macrophage-like cells was semiquantitatively assessed by CD68 staining in the ischaemic area and ischaemic border zone, and linked to the clinical course. CD11b, ionized calcium binding adaptor molecule 1 (Iba), glial fibrillary acidic protein (GFAP) and Neuronal Nuclei (NeuN) were applied to reveal delayed glial and neuronal alterations. In all groups, the accumulation of macrophage-like cells increased distinctly from 24 hours to 7 days post ischaemia. tPA+HBO tended to decrease macrophage-like cell accumulation at day 14 and 28. Overall, a trend towards an association of increased accumulation and pronounced reduction of the neurological deficit was found. Concerning delayed inflammatory reactions, an activation of microglia and astrocytes with co-occurring neuronal loss was observed on day 28. Thereby, astrogliosis was found circularly in contrast to microglial activation directly in the ischaemic area. This study supports previous data on long-lasting inflammatory processes following experimental stroke, and additionally provides region-specific details on glial reactions. The tendency towards a decreasing macrophage-like cell accumulation after tPA+HBO needs to be discussed

  13. Enhanced recovery from chronic ischemic injury by bone marrow cells in a rat model of ischemic stroke.

    PubMed

    Yoo, Jongman; Seo, Jin-Ju; Eom, Jang-Hyeon; Hwang, Dong-Youn

    2015-01-01

    Even after decades of intensive studies, therapeutic options for patients with stroke are rather limited. Thrombolytic drugs effectively treat the very acute stage of stroke, and several neuroprotectants that are designed to treat secondary injury following stroke are being tested in clinical trials. However, these pharmacological approaches primarily focus on acute stroke recovery, and few options are available for treating chronic stroke patients. In recent years, stem cell-mediated regenerative approaches have emerged as promising therapeutic strategies for treating the chronic stage of stroke. In this study, we examined whether systemically administered bone marrow cells (BMCs) could have beneficial effects in a rat model of chronic ischemia. Our transplantation experiments using BMCs obtained from ischemic donor rats showed functional and structural recovery during the chronic stage of stroke. BMC-mediated neural proliferation was prominent in the brains of rats with chronic stroke, and most of the new cells eventually became neurons instead of astrocytes. BMC-mediated enhanced neural proliferation coincided with a significant reduction (∼50%) in the number of activated microglia, which is consistent with previous reports of enhanced neural proliferation being linked to microglial inactivation. Strikingly, approximately 57% of the BMCs that infiltrated the chronic ischemic brain were CD25(+) cells, suggesting that these cells may exert the beneficial effects associated with BMC transplantation. Based on the reported anti-inflammatory role of CD25(+) regulatory T-cells in acute experimental stroke, we propose a working model delineating the positive effects of BMC transplantation during the chronic phase of stroke; infiltrating BMCs (mostly CD25(+) cells) reduce activated microglia, which leads to enhanced neural proliferation and enhanced recovery from neuronal damage in this rat model of chronic stroke. This study provides valuable insights into the effect

  14. Animal Models for Therapeutic Embolization

    SciTech Connect

    Moreira, Patricia L.; An, Yuehuei H.

    2003-04-15

    Embolization techniques have been performed in different animals to accumulate basic data before a clinical trial.Choosing the right embolization model for a specific project is critical. However, there are several variables when defining the best model for embolization research such as the size of the animal to be used, the target organs, the route of introducing the embolization agent, and the feasible methods of evaluation. Commonly used research animals for endovascular embolization include rabbits, dogs, and rats. Frequently used target organs are the kidney and the liver. Most models use a transcatheter for introducing the embolus and occasionally open surgery and direct arterial injection are used. Basic methods of evaluation are straightforward, and commonly include macro observation of the embolized organs, angiogram, and histology. This article concisely reviews the available animal models and their evaluation for embolization research to help researchers to choose the appropriate model.

  15. MicroRNA-493 regulates angiogenesis in a rat model of ischemic stroke by targeting MIF.

    PubMed

    Li, Qian; He, Quanwei; Baral, Suraj; Mao, Ling; Li, Yanan; Jin, Huijuan; Chen, Shengcai; An, Tianhui; Xia, Yuanpeng; Hu, Bo

    2016-05-01

    MicroRNA-493 (miR-493) is known to suppress tumour metastasis and angiogenesis and its expression is decreased in stroke patients. In the present study, we investigated a role for miR-493 in regulating post-stroke angiogenesis. We found decreased expression of miR-493 in the ischemic boundary zone (IBZ) of rats subjected to middle cerebral artery occlusion (MCAO), and in rat brain microvascular endothelial cells (RBMECs) exposed to oxygen glucose deprivation. Down-regulating miR-493 with a lateral ventricular injection of antagomir-493, a synthetic miR-493 inhibitor, increased capillary density in the IBZ, decreased focal infarct volume and ameliorated neurologic deficits in rats subjected to MCAO. Intriguingly, MCAO also increased the expression of macrophage migration inhibitory factor (MIF) in the IBZ of rats; MIF expression was also increased in RBMECs exposed to oxygen glucose deprivation. We found that miR-493 directly targeted MIF, and that the protective effect of miR-493 inhibition in angiogenesis was attenuated by knocking down MIF. This effect could then be rescued by administration of recombinant MIF. Our findings highlight the importance of miR-493 in regulating angiogenesis after MCAO, and indicate that miR-493 is a potential therapeutic target in the treatment of stroke. PMID:26929185

  16. Symptomatological classification in the development of stroke in stroke-prone spontaneously hypertensive rats.

    PubMed

    Yamori, Y; Horie, R; Akiguchi, I; Kihara, M; Nara, Y; Lovenberg, W

    1982-03-01

    The developmental course of cerebrovascular diseases was examined by comparative neurological and pathological studies in stroke-prone SHR (SHRSP) which died spontaneously or were sacrificed. Behavioral status during their life span could be simply divided into 4 patterns, i.e., "no abnormalities", "irritable", "lethergic" and "akinetic" named Grades 0, I, II and III, respectively (Yamori's Classification). Grades I, II and III of behavioral status corresponded well to symptomato-pathoanatomically divided 3 stages (relating to brain edema), i.e., Stages I, II and III, respectively. PMID:7199593

  17. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke.

    PubMed

    Khodaparast, Navid; Hays, Seth A; Sloan, Andrew M; Fayyaz, Tabbassum; Hulsey, Daniel R; Rennaker, Robert L; Kilgard, Michael P

    2014-09-01

    Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. PMID:24553102

  18. Does Mechanical Thrombectomy in Acute Embolic Stroke Have Long-term Side Effects on Intracranial Vessels? An Angiographic Follow-up Study

    SciTech Connect

    Kurre, Wiebke Perez, Marta Aguilar; Horvath, Diana; Schmid, Elisabeth; Baezner, Hansjoerg; Henkes, Hans

    2013-06-15

    Purpose. Mechanical thrombectomy (mTE) proved to be effective treating acute vessel occlusions with an acceptable rate of procedural complications. Potential long-term side effects of the vessel wall trauma caused by mechanical irritation of the endothelium are unknown up to now. Methods. From a retrospectively established database of 640 acute stroke treatments, we selected 261 patients with 265 embolic vessel occlusions treated successfully by mTE without permanent implantation of a stent. Analysis comprised the type of devices used and the number of passes performed. Digital subtraction angiography immediately after treatment was evaluated for vasospasm, dissection, and extravasation. Control angiographic images were evaluated for any morphological change compared to the immediate posttreatment angiographic run. Results. Recanalization was achieved with a median of one (range 1-10) mTE maneuvers. Vasospasm occurred in 69 territories (26.0 %) and was treated with glyceroltrinitrate in three. Dissection was observed in one vessel (0.4 %). Intraprocedural hemorrhage in two patients (0.8 %) was either wire or device induced. Follow-up digital subtraction angiography was available for 117 territories after a median of 107 days, revealing target vessel occlusion in one segment (0.9 %) and a de novo stenosis of four segments (3.4 %). All findings were clinically asymptomatic. Posttreatment vasospasm was more frequent in patients with de novo stenosis and occlusion (p = 0.038). Conclusion. De novo stenoses and occlusions occur in a small proportion of patients after mTE. Because all lesions were clinically asymptomatic, this finding does not affect the overall benefit of the treatment. Vasospasm may predict late vessel wall changes.

  19. Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke

    PubMed Central

    Duricki, Denise A.; Hutson, Thomas H.; Kathe, Claudia; Soleman, Sara; Gonzalez-Carter, Daniel; Petruska, Jeffrey C.; Shine, H. David; Chen, Qin; Wood, Tobias C.; Bernanos, Michel; Cash, Diana; Williams, Steven C. R.; Gage, Fred H.

    2016-01-01

    There is an urgent need for a therapy that reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. We show here that intramuscular delivery of neurotrophin-3 (NT3, encoded by NTF3) can induce sensorimotor recovery when treatment is initiated 24 h after stroke. Specifically, in two randomized, blinded preclinical trials, we show improved sensory and locomotor function in adult (6 months) and elderly (18 months) rats treated 24 h following cortical ischaemic stroke with human NT3 delivered using a clinically approved serotype of adeno-associated viral vector (AAV1). Importantly, AAV1-hNT3 was given in a clinically-feasible timeframe using a straightforward, targeted route (injections into disabled forelimb muscles). Magnetic resonance imaging and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, treatment caused corticospinal axons from the less affected hemisphere to sprout in the spinal cord. This treatment is the first gene therapy that reverses disability after stroke when administered intramuscularly in an elderly body. Importantly, phase I and II clinical trials by others show that repeated, peripherally administered high doses of recombinant NT3 are safe and well tolerated in humans with other conditions. This paves the way for NT3 as a therapy for stroke. PMID:26614754

  20. Induction and imaging of photothrombotic stroke in conscious and freely moving rats

    NASA Astrophysics Data System (ADS)

    Lu, Hongyang; Li, Yao; Yuan, Lu; Li, Hangdao; Lu, Xiaodan; Tong, Shanbao

    2014-09-01

    In experimental stroke research, anesthesia is common and serves as a major reason for translational failure. Real-time cerebral blood flow (CBF) monitoring during stroke onset can provide important information for the prediction of brain injury; however, this is difficult to achieve in clinical practice due to various technical problems. We created a photothrombotic focal ischemic stroke model utilizing our self-developed miniature headstage in conscious and freely moving rats. In this model, a high spatiotemporal resolution imager using laser speckle contrast imaging technology was integrated to acquire real-time two-dimensional CBF information during thrombosis. The feasibility, stability, and reliability of the system were tested in terms of CBF, behavior, and T2-weighted magnetic resonance imaging (MRI) findings. After completion of occlusion, the CBF in the targeted cortex of the stroke group was reduced to 16±9% of the baseline value. The mean infarct volume measured by MRI 24 h postmodeling was 77±11 mm3 and correlated well with CBF (R2=0.74). This rodent model of focal cerebral ischemia and real-time blood flow imaging opens the possibility of performing various fundamental and translational studies on stroke without the influence of anesthetics.

  1. Characterization of Behaviour and Remote Degeneration Following Thalamic Stroke in the Rat

    PubMed Central

    Weishaupt, Nina; Riccio, Patricia; Dobbs, Taylor; Hachinski, Vladimir C.; Whitehead, Shawn N.

    2015-01-01

    Subcortical ischemic strokes are among the leading causes of cognitive impairment. Selective atrophy of remote brain regions connected to the infarct is thought to contribute to deterioration of cognitive functions. The mechanisms underlying this secondary degenerative process are incompletely understood, but are thought to include inflammation. We induce ischemia by unilateral injection of endothelin-I into the rat dorsomedial thalamic nucleus, which has defined reciprocal connections to the frontal cortex. We use a comprehensive test battery to probe for changes in behaviour, including executive functions. After a four-week recovery period, brain sections are stained with markers for degeneration, microglia, astrocytes and myelin. Degenerative processes are localized within the stroke core and along the full thalamocortical projection, which does not translate into measurable behavioural deficits. Significant microglia recruitment, astrogliosis or myelin loss along the axonal projection or within the frontal cortex cannot be detected. These findings indicate that critical effects of stroke-induced axonal degeneration may only be measurable beyond a threshold of stroke severity and/or follow a different time course. Further investigations are needed to clarify the impact of inflammation accompanying axonal degeneration on delayed remote atrophy after stroke. PMID:26090717

  2. Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke.

    PubMed

    Duricki, Denise A; Hutson, Thomas H; Kathe, Claudia; Soleman, Sara; Gonzalez-Carter, Daniel; Petruska, Jeffrey C; Shine, H David; Chen, Qin; Wood, Tobias C; Bernanos, Michel; Cash, Diana; Williams, Steven C R; Gage, Fred H; Moon, Lawrence D F

    2016-01-01

    There is an urgent need for a therapy that reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. We show here that intramuscular delivery of neurotrophin-3 (NT3, encoded by NTF3) can induce sensorimotor recovery when treatment is initiated 24 h after stroke. Specifically, in two randomized, blinded preclinical trials, we show improved sensory and locomotor function in adult (6 months) and elderly (18 months) rats treated 24 h following cortical ischaemic stroke with human NT3 delivered using a clinically approved serotype of adeno-associated viral vector (AAV1). Importantly, AAV1-hNT3 was given in a clinically-feasible timeframe using a straightforward, targeted route (injections into disabled forelimb muscles). Magnetic resonance imaging and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, treatment caused corticospinal axons from the less affected hemisphere to sprout in the spinal cord. This treatment is the first gene therapy that reverses disability after stroke when administered intramuscularly in an elderly body. Importantly, phase I and II clinical trials by others show that repeated, peripherally administered high doses of recombinant NT3 are safe and well tolerated in humans with other conditions. This paves the way for NT3 as a therapy for stroke. PMID:26614754

  3. Characterization of Behaviour and Remote Degeneration Following Thalamic Stroke in the Rat.

    PubMed

    Weishaupt, Nina; Riccio, Patricia; Dobbs, Taylor; Hachinski, Vladimir C; Whitehead, Shawn N

    2015-01-01

    Subcortical ischemic strokes are among the leading causes of cognitive impairment. Selective atrophy of remote brain regions connected to the infarct is thought to contribute to deterioration of cognitive functions. The mechanisms underlying this secondary degenerative process are incompletely understood, but are thought to include inflammation. We induce ischemia by unilateral injection of endothelin-I into the rat dorsomedial thalamic nucleus, which has defined reciprocal connections to the frontal cortex. We use a comprehensive test battery to probe for changes in behaviour, including executive functions. After a four-week recovery period, brain sections are stained with markers for degeneration, microglia, astrocytes and myelin. Degenerative processes are localized within the stroke core and along the full thalamocortical projection, which does not translate into measurable behavioural deficits. Significant microglia recruitment, astrogliosis or myelin loss along the axonal projection or within the frontal cortex cannot be detected. These findings indicate that critical effects of stroke-induced axonal degeneration may only be measurable beyond a threshold of stroke severity and/or follow a different time course. Further investigations are needed to clarify the impact of inflammation accompanying axonal degeneration on delayed remote atrophy after stroke. PMID:26090717

  4. Autonomic and myocardial changes in middle cerebral artery occlusion: stroke models in the rat.

    PubMed

    Cechetto, D F; Wilson, J X; Smith, K E; Wolski, D; Silver, M D; Hachinski, V C

    1989-11-20

    Stroke models in larger animals such as the cat, dog and monkey are becoming increasingly more expensive and less readily available. However, the rat is an excellent model for focal cerebral ischemia. Rats are readily available, inexpensive and their neuroanatomy and brain function have been studied extensively. Increases in plasma catecholamines and myocardial damage have been observed in clinical stroke. We examined autonomic and myocardial changes in two rat stroke models. In one model only the middle cerebral artery was occluded (MCAO) while the other model involved occlusion of both the MCA and the common carotid artery (MCAO/CCAO). Arterial blood pressure and heart rate were monitored continuously in 25 male rats (326-430 g) that underwent one of the following procedures: (1) MCAO only; (2) MCAO/CCAO; (3) CCAO only; and (4) sham occlusions (SHAM). Arterial blood samples (0.5 ml) for radioenzymatic assay of norepinephrine (NE) and epinephrine (E) were taken twice before the occlusions and at 90 and 180 min after the occlusions. The animals were perfused at the end of the experiment and the heart removed and examined histologically. Tetrazolium salts were reacted with oxidative enzymes to delineate the region of inadequate perfusion. The mean blood pressure and pulse pressure of the SHAM, MCAO/CCAO and CCAO groups significantly declined from initial values (from an average of 78 to 53 mm Hg) during the course of the experiment. However, the mean blood pressure and pulse pressure of the MCAO rats did not change during the experiment, so that the final mean blood pressure and pulse pressure were significantly higher than in the other 3 groups. The levels of both NE and E increased significantly (NE, 1443 +/- 285.9 to 4095 +/- 929 pg/ml; E, 2402 +/- 623 to 3741 +/- 1166 pg/ml) following occlusion in the MCAO group only while the other 3 groups did not change. Four of 6 hearts in the MCAO group were abnormal, showing evidence of subendocardial hemorrhage, ischemic

  5. A new NOE-mediated MT signal at around -1.6ppm for detecting ischemic stroke in rat brain.

    PubMed

    Zhang, Xiao-Yong; Wang, Feng; Afzal, Aqeela; Xu, Junzhong; Gore, John C; Gochberg, Daniel F; Zu, Zhongliang

    2016-10-01

    In the present work, we reported a new nuclear Overhauser enhancement (NOE)-mediated magnetization transfer (MT) signal at around -1.6ppm (NOE(-1.6)) in rat brain and investigated its application in the detection of acute ischemic stroke in rodent model. Using continuous wave (CW) MT sequence, the NOE(-1.6) is reliably detected in rat brain. The amplitude of this new NOE signal in rat brain was quantified using a 5-pool Lorentzian Z-spectral fitting method. Amplitudes of amide, amine, NOE at -3.5ppm (NOE(-3.5)), as well as NOE(-1.6) were mapped using this fitting method in rat brain. Several other conventional imaging parameters (R1, R2, apparent diffusion coefficient (ADC), and semi-solid pool size ratio (PSR)) were also measured. Our results show that NOE(-1.6), R1, R2, ADC, and APT signals from stroke lesion have significant changes at 0.5-1h after stroke. Compared with several other imaging parameters, NOE(-1.6) shows the strongest contrast differences between stroke and contralateral normal tissues and stays consistent over time until 2h after onset of stroke. Our results demonstrate that this new NOE(-1.6) signal in rat brain is a new potential contrast for assessment of acute stroke in vivo and might provide broad applications in the detection of other abnormal tissues. PMID:27211260

  6. Pulmonary Embolism

    MedlinePlus

    ... pulmonary embolism is a sudden blockage in a lung artery. The cause is usually a blood clot ... loose and travels through the bloodstream to the lung. Pulmonary embolism is a serious condition that can ...

  7. Hyperpolarized 129Xe magnetic resonance imaging of a rat model of transient Ischemic Stroke

    NASA Astrophysics Data System (ADS)

    Walvick, Ronn P.; Bastan, Birgul; Reno, Austin; Mansour, Joey; Sun, Yanping; Zhou, Xin; Mazzani, Mary; Fisher, Marc; Sotak, Christopher H.; Albert, Mitchell S.

    2009-02-01

    Ischemic stroke accounts for nearly 80% of all stroke cases. Although proton diffusion and perfusion magnetic resonance imaging (MRI) are the gold standards in ischemic stroke diagnostics, the use of hyperpolarized 129Xe MRI has a potential role to contribute to the diagnostic picture. The highly lipophilic hyperpolarized 129Xe can be non-invasively delivered via inhalation into the lungs where it is dissolved into the blood and delivered to other organs such as the brain. As such, we expect hyperpolarized 129Xe to act as a perfusion tracer which will result in a signal deficit in areas of blood deprived tissue. In this work, we present imaging results from an animal model of transient ischemic stroke characterized through 129Xe MRI. In this model, a suture is used to occlude the middle cerebral artery (MCA) in the rat brain, thus causing an ischemic event. After a period of MCA occlusion, the suture can then be removed to reperfuse the ischemic area. During the ischemic phase of the stroke, a signal void was observed in the MCA territory; which was subsequently restored by normal 129Xe MRI signal once perfusion was reinstated. Further, a higher resolution one-dimensional chemical shift image shows a sharp signal drop in the area of ischemia. Validation of ischemic damage was shown through both proton diffusion-weighted MRI (DWI) and by 2,3,5-triphenyltetrazoliumchloride (TTC) staining. The results show the potential of 129Xe to act as a perfusion tracer; information that may add to the diagnostic and prognostic utility of the clinical picture of stroke.

  8. Pulmonary Embolism.

    PubMed

    Rali, Parth; Gandhi, Viral; Malik, Khalid

    2016-01-01

    Pulmonary embolism covers a wide spectrum of presentation from an asymptomatic individual to a life-threatening medical emergency. It is of paramount importance to appropriately risk stratify patients with pulmonary embolism, particularly with those who present without hypotension. Right ventricular dysfunction can evolve after a patient has received a diagnosis of pulmonary embolism, necessitating aggressive measures rather than simple anticoagulation. In this review, we discuss definition, risk stratification, pathogenesis, diagnostic approach, and management, with particular focus on massive pulmonary embolism. PMID:26919674

  9. The Effect of Electromagnetic Field Treatment on Recovery from Ischemic Stroke in a Rat Stroke Model: Clinical, Imaging, and Pathological Findings.

    PubMed

    Segal, Y; Segal, L; Blumenfeld-Katzir, T; Sasson, E; Poliansky, V; Loeb, E; Levy, A; Alter, A; Bregman, N

    2016-01-01

    Stroke is a leading cause of death and disability. Effects of stroke include significant deficits in sensory-motor skills and cognitive abilities. At present, there are limited effective interventions for postacute stroke patients. In this preliminary research we studied a new noninvasive, very low intensity, low frequency, electromagnetic field treatment (VLIFE), targeting a neural network, on an in vivo stroke rat model. Eighteen rats were divided into three groups: sham (M1) and two treatment groups which were exposed to VLIFE treatment for 4 weeks, one using theta waves (M2) and another using beta waves (M3); all groups were followed up for an additional month. Results indicate that the M2 and M3 treated groups showed recovery of sensorimotor functional deficits, as demonstrated by Modified Neurological Severity Score and forelimb placement tests. Brain MRI imaging results show a decrease in perilesional edema and lateral ventricle widening in the treated groups. Fiber tracts' imaging, following VLIFE treatment, showed a higher white matter integrity compared to control. Histological findings support neural regeneration processes. Our data suggest that VLIFE treatment, targeting a specific functional neural network by frequency rather than location, promotes neuronal plasticity after stroke and, as a result, improves clinical recovery. Further studies will investigate the full potential of the treatment. PMID:26949561

  10. The Effect of Electromagnetic Field Treatment on Recovery from Ischemic Stroke in a Rat Stroke Model: Clinical, Imaging, and Pathological Findings

    PubMed Central

    Segal, Y.; Segal, L.; Blumenfeld-Katzir, T.; Sasson, E.; Poliansky, V.; Loeb, E.; Levy, A.; Alter, A.; Bregman, N.

    2016-01-01

    Stroke is a leading cause of death and disability. Effects of stroke include significant deficits in sensory-motor skills and cognitive abilities. At present, there are limited effective interventions for postacute stroke patients. In this preliminary research we studied a new noninvasive, very low intensity, low frequency, electromagnetic field treatment (VLIFE), targeting a neural network, on an in vivo stroke rat model. Eighteen rats were divided into three groups: sham (M1) and two treatment groups which were exposed to VLIFE treatment for 4 weeks, one using theta waves (M2) and another using beta waves (M3); all groups were followed up for an additional month. Results indicate that the M2 and M3 treated groups showed recovery of sensorimotor functional deficits, as demonstrated by Modified Neurological Severity Score and forelimb placement tests. Brain MRI imaging results show a decrease in perilesional edema and lateral ventricle widening in the treated groups. Fiber tracts' imaging, following VLIFE treatment, showed a higher white matter integrity compared to control. Histological findings support neural regeneration processes. Our data suggest that VLIFE treatment, targeting a specific functional neural network by frequency rather than location, promotes neuronal plasticity after stroke and, as a result, improves clinical recovery. Further studies will investigate the full potential of the treatment. PMID:26949561

  11. Combination treatment of r- tPA and an optimized human apyrase reduces mortality rate and hemorrhagic transformation 6h after ischemic stroke in aged female rats

    PubMed Central

    Tan, Zhenjun; Li, Xinlan; Turner, Ryan C; Logsdon, Aric F; Lucke-Wold, Brandon; DiPasquale, Kenneth; Jeong, Soon Soeg; Chen, Ridong; Huber, Jason D; Rosen, Charles L

    2014-01-01

    Recombinant tissue plasminogen activator (r-tPA) is the only FDA-approved drug treatment for ischemic stroke and must be used within 4.5 hours. Thrombolytic treatment with r-tPA has deleterious effects on the neurovascular unit that substantially increases the risk of intracerebral hemorrhage if administered too late. These therapeutic shortcomings necessitate additional investigation into agents that can extend the therapeutic window for safe use of thrombolytics. In this study, combination of r-tPA and APT102, a novel form of human apyrase/ADPase, was investigated in a clinically-relevant aged-female rat embolic ischemic stroke model. We propose that successfully extending the therapeutic window of r-tPA administration would represent a significant advance in the treatment of ischemic stroke due to a significant increase in the number of patients eligible for treatment. Results of our study showed significantly reduced mortality from 47% with r-tPA alone to 16% with co-administration of APT102 and r-tPA. Co-administration decreased cortical (47±5% vs 29±5%), striatal (50±2%, vs 40±3%) and total (48±3%vs 33±4%) hemispheric infarct volume compared to r-tPA alone. APT102 improved neurological outcome (8.9±0.6, vs 6.8±0.8) and decreased hemoglobin extravasation in cortical tissue (1.9±0.1 mg/dlvs 1.4±0.1 mg/dl) striatal tissue (2.1±0.3 mg/dl vs 1.4±0.1 mg/dl) and whole brain tissue (2.0±0.2 mg/dl vs 1.4±0.1 mg/dl). These data suggest that APT102 can safely extend the therapeutic window for r-tPA mediated reperfusion to 6 h following experimental stroke without increased hemorrhagic transformation. APT102 offers to be a viable adjunct therapeutic option to increase the number of clinical patients eligible for thrombolytic treatment after ischemic stroke. PMID:24933645

  12. Endocarditis and Stroke

    PubMed Central

    GRECU, Nicolae; TIU, Cristina; TERECOASA, Elena; BAJENARU, Ovidiu

    2014-01-01

    Endocarditis is an important, although less common, cause of cerebral embolism. All forms of endocarditis share an initial common pathophysiologic pathway, best illustrated by the non-bacterial thrombotic form, but also a final potential for embolization. Stroke associated with endocarditis has signifficant mortality and morbidity rates, especially due to the frequent concomitant multiple sites of brain embolization. In this article we aim to briefly review endocarditis with a focus on stroke as a complication, while also presenting case correlates from our department. PMID:25705308

  13. Intracranial Pressure Elevation 24 h after Ischemic Stroke in Aged Rats Is Prevented by Early, Short Hypothermia Treatment

    PubMed Central

    Murtha, Lucy A.; Beard, Daniel J.; Bourke, Julia T.; Pepperall, Debbie; McLeod, Damian D.; Spratt, Neil J.

    2016-01-01

    Stroke is predominantly a senescent disease, yet most preclinical studies investigate treatment in young animals. We recently demonstrated that short-duration hypothermia-treatment completely prevented the dramatic intracranial pressure (ICP) rise seen post-stroke in young rats. Here, our aim was to investigate whether a similar ICP rise occurs in aged rats and to determine whether short-duration hypothermia is an effective treatment in aged animals. Experimental middle cerebral artery occlusion (MCAo-3 h occlusion) was performed on male Wistar rats aged 19–20 months. At 1 h after stroke-onset, rats were randomized to 2.5 h hypothermia-treatment (32.5°C) or normothermia (37°C). ICP was monitored at baseline, for 3.5 h post-occlusion, and at 24 h post-stroke. Infarct and edema volumes were calculated from histology. Baseline pre-stroke ICP was 11.2 ± 3.3 mmHg across all animals. Twenty-four hours post-stroke, ICP was significantly higher in normothermic animals compared to hypothermia-treated animals (27.4 ± 18.2 mmHg vs. 8.0 ± 5.0 mmHg, p = 0.03). Infarct and edema volumes were not significantly different between groups. These data demonstrate ICP may also increase 24 h post-stroke in aged rats, and that short-duration hypothermia treatment has a profound and sustained preventative effect. These findings may have important implications for the use of hypothermia in clinical trials of aged stroke patients. PMID:27303291

  14. Copolymer-1 Promotes Neurogenesis and Improves Functional Recovery after Acute Ischemic Stroke in Rats

    PubMed Central

    Cruz, Yolanda; Lorea, Jonathan; Mestre, Humberto; Kim-Lee, Jennifer Hyuna; Herrera, Judith; Mellado, Raúl; Gálvez, Vanesa; Cuellar, Leopoldo; Musri, Carolina; Ibarra, Antonio

    2015-01-01

    Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurogenesis (at 7 and 60 days) in the SVZ, SGZ, and cerebral cortex through an increase in NT-3 production. It also decreased infarct volume even at the chronic phase of tMCAo. The present manuscript fortifies the support for the use of Cop-1 in acute ischemic stroke. PMID:25821957

  15. Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model

    PubMed Central

    Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Frisina-Deyo, Aric; Boffeli, Sean M.; Abraham, Jerry V.; Pabon, Mibel; Wagner, Andrew; Ishikawa, Hiroto; Shinozuka, Kazutaka; Haller, Edward; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesario V.

    2013-01-01

    Background Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. Methodology/Principal Findings In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. Conclusions/Significance These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke. PMID:23675488

  16. Copolymer-1 promotes neurogenesis and improves functional recovery after acute ischemic stroke in rats.

    PubMed

    Cruz, Yolanda; Lorea, Jonathan; Mestre, Humberto; Kim-Lee, Jennifer Hyuna; Herrera, Judith; Mellado, Raúl; Gálvez, Vanesa; Cuellar, Leopoldo; Musri, Carolina; Ibarra, Antonio

    2015-01-01

    Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurogenesis (at 7 and 60 days) in the SVZ, SGZ, and cerebral cortex through an increase in NT-3 production. It also decreased infarct volume even at the chronic phase of tMCAo. The present manuscript fortifies the support for the use of Cop-1 in acute ischemic stroke. PMID:25821957

  17. Airplane stroke syndrome.

    PubMed

    Humaidan, Hani; Yassi, Nawaf; Weir, Louise; Davis, Stephen M; Meretoja, Atte

    2016-07-01

    Only 37 cases of stroke during or soon after long-haul flights have been published to our knowledge. In this retrospective observational study, we searched the Royal Melbourne Hospital prospective stroke database and all discharge summaries from 1 September 2003 to 30 September 2014 for flight-related strokes, defined as patients presenting with stroke within 14days of air travel. We hypothesised that a patent foramen ovale (PFO) is an important, but not the only mechanism, of flight-related stroke. We describe the patient, stroke, and flight characteristics. Over the study period, 131 million passengers arrived at Melbourne airport. Our centre admitted 5727 stroke patients, of whom 42 (0.73%) had flight-related strokes. Flight-related stroke patients were younger (median age 65 versus 73, p<0.001), had similar stroke severity, and received intravenous thrombolysis more often than non-flight-related stroke patients. Seven patients had flight-related intracerebral haemorrhage. The aetiology of the ischaemic strokes was cardioembolic in 14/35 (40%), including seven patients with confirmed PFO, one with atrial septal defect, four with atrial fibrillation, one with endocarditis, and one with aortic arch atheroma. Paradoxical embolism was confirmed in six patients. Stroke related to air travel is a rare occurrence, less than one in a million. Although 20% of patients had a PFO, distribution of stroke aetiologies was diverse and was not limited to PFO and paradoxical embolism. PMID:26898578

  18. [Intervention effect of Tibetan patent medicine Ruyi Zhenbao pills in acute ischemic stroke in rats].

    PubMed

    Liu, Rui-ying; Wu, Wei-jie; Tan, Rui; Xie, Bin; Zhong, Zhen-dong; He, Jing-ping; Chen, Yao; Kang, Xin-li

    2015-02-01

    Ischemic stroke is a primary cause of death and long-term disability all over the world. This disease is resulted from ischemia and hypoxia in brain tissues because of insufficient blood supply and causes a series of physiochemical metabolism disorders and physiological dysfunction. Its high disability ratio has bright huge burdens to society, governments and families. However, there is not efficacious medicine to treat it. In this study, a right middle cerebral artery occlusion was established in rats to observe the multi-path and multi-aspect intervention effects of Tibetan patent medicine Ruyi Zhenbao pills in reducing injuries to Nissl bodies, cerebral edema and inflammatory reactions and preventing cellular apoptosis, in order to lay a foundation for defining its therapeutic mechanism in acute ischemic stroke. PMID:26084187

  19. Examining the Role of Endogenous Opioids in Learned Odor-Stroke Associations in Infant Rats

    PubMed Central

    Roth, Tania L.; Sullivan, Regina M.

    2006-01-01

    Maternal touch profoundly regulates infant neural and behavioral development, and supports learned odor associations necessary for infant attachment. Endogenous opioids are well characterized to mediate the calming and analgesic properties of maternal touch; yet their role in learned odor-touch associations is unknown. We administered naltrexone, an opioid receptor antagonist, before or immediately following classical conditioning with peppermint odor and tactile stimulation (stroking) in rat neonates. Results indicate odor-stroke conditioning produces odor preferences facilitated by endogenous opioids during acquisition and memory consolidation. These results provide additional evidence for the modulatory role of opioids in neonate learning and memory. Disturbances to this system may alter the impact of touch on infant development, particularly in the realm of learning necessary for attachment. PMID:16381030

  20. Neuronal repair. Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke.

    PubMed

    Wahl, A S; Omlor, W; Rubio, J C; Chen, J L; Zheng, H; Schröter, A; Gullo, M; Weinmann, O; Kobayashi, K; Helmchen, F; Ommer, B; Schwab, M E

    2014-06-13

    The brain exhibits limited capacity for spontaneous restoration of lost motor functions after stroke. Rehabilitation is the prevailing clinical approach to augment functional recovery, but the scientific basis is poorly understood. Here, we show nearly full recovery of skilled forelimb functions in rats with large strokes when a growth-promoting immunotherapy against a neurite growth-inhibitory protein was applied to boost the sprouting of new fibers, before stabilizing the newly formed circuits by intensive training. In contrast, early high-intensity training during the growth phase destroyed the effect and led to aberrant fiber patterns. Pharmacogenetic experiments identified a subset of corticospinal fibers originating in the intact half of the forebrain, side-switching in the spinal cord to newly innervate the impaired limb and restore skilled motor function. PMID:24926013

  1. A Novel Cell Therapy Method for Recovering after Brain Stroke in Rats

    PubMed Central

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Kazemi, Sepehr; Shakibajahromi, Benafshe; Sarvestani, Fatemeh Sabet; Khodabande, Zahra

    2015-01-01

    Background Nowadays, stroke leads to a significant part of the adult mortality and morbidity and also it could result in some neurological deficits in the patients’ lives. Cell therapy has opened a new approach to treat the brain ischemia and reduce its terrible effects on the patients’ lives. There are several articles which show that the cell therapy could be beneficial for treating brain stroke. In this study, we have planned to present a new cell therapy method for stroke by administration of Mesenchymal stem cells and differentiated neural stem cells without astrocytes. Method and Materials The Mesenchymal stem cells were isolated from tibia and femur of a 250~300 g rat and they were cultured in DMEM/F12, 10% fetal bovine serum, 1% Pen/Strep. Neural stem cells were isolated from 14 days rat embryo ganglion eminence and were cultured in NSA media containing Neurobasal, 2% B27, bFGF 10 ng/ml and EGF 20 ng/ml after 5 days they formed some neurospheres. The isolated neural stem cells were differentiated to neural lineages by adding 5% fetal bovine serum to their culture media. After 48 hours the astrocytes were depleted by using MACS kit. Results The group that received Mesenchymal stem cells systemically and differentiated neural stem cells without astrocytes had the best neurological outcomes and the least infarct volume and apoptosis. It could be understood that this cell therapy method might cause almost full recovery after brain stoke. Conclusion Using combination cell therapy with Mesenchymal stem cells and differentiated neural stem cells with removed astrocyte could provide a novel method for curing brain stroke. PMID:26634067

  2. Nafamostat mesilate improves function recovery after stroke by inhibiting neuroinflammation in rats.

    PubMed

    Li, Chenhui; Wang, Jing; Fang, Yinquan; Liu, Yuan; Chen, Tao; Sun, Hao; Zhou, Xin-Fu; Liao, Hong

    2016-08-01

    Inflammation plays an important role in stroke pathology, making it a promising target for stroke intervention. Nafamostat mesilate (NM), a wide-spectrum serine protease inhibitor, is commonly used for treating inflammatory diseases, such as pancreatitis. However, its effect on neuroinflammation after stroke was unknown. Hence, the effects of NM on the inflammatory response post stroke were characterized. After transient middle cerebral artery occlusion (tMCAO) in rats, NM reduced the infarct size, improved behavioral functions, decreased the expression of proinflammatory mediators (TNF-α, IL-1β, iNOS and COX-2) in a time-dependent manner and promoted the expression of different anti-inflammatory factors (CD206, TGF-β, IL-10 and IL-4) at different time points. Furthermore, NM could inhibit the expression of proinflammatory mediators and promote anti-inflammatory mediators expression in rat primary microglia following exposure to thrombin combined with oxygen-glucose deprivation (OGD). The immune-modulatory effect of NM might be partly due to its inhibition of the NF-κB signaling pathway and inflammasome activation after tMCAO. In addition, NM significantly inhibited the infiltration of macrophage, neutrophil and T lymphocytes, which was partly mediated by the inhibition of monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Taken together, our results indicated that NM can provide long-term protection of the brain against tMCAO by modulating a broad components of the inflammatory response. PMID:27033633

  3. Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke

    PubMed Central

    Kampschulte, Marian; Hyvelin, Jean-Marc; Botteron, Catherine; Juenemann, Martin; Yeniguen, Mesut; Krombach, Gabriele A.; Kaps, Manfred; Spratt, Neil J.; Gerriets, Tibo; Nedelmann, Max

    2016-01-01

    Background Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model. Methods We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography. Results Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p<0.05), but was not significantly different from the contralateral hemisphere in all microbubble-treated groups (p>0.1). Conclusions Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory. PMID:27077372

  4. M1 macrophage infiltrations and histological changes in the liver after portal vein embolization using fibrinogen and OK432 in the rat.

    PubMed

    Sato, Tetsu; Marubashi, Shigeru; Kenjo, Akira; Tsuchiya, Takao; Kimura, Takashi; Sato, Naoya; Watanabe, Junichiro; Tasaki, Kazuhiro; Hashimoto, Yuko; Wada, Ikuo; Gotoh, Mitsukazu

    2016-05-01

    The mechanism of anti-tumor effect of transarterial Immuno-Embolization (TIE) using OK-432 has not been well elucidated. In this study, we aimed to investigate the tissue injury and immune response after portal venous embolization (PVE) with/without OK-432. Embolic materials (L group: lipiodol, LF group: lipiodol+fibrinogen, LO group: lipiodol+OK-432, LFO group: lipiodol+fibrinogen+OK-432) were administered via the right portal vein in Wistar rats. The histological findings in LFO group demonstrated liver damage with severe architectural changes. The concentrations of CD68(+) cells were observed in a time-dependent manner; it was significantly increased in the LO group on day 1 and in the LFO group on day 3. CD68(+)CD163(-) macrophages significantly increased in the LFO group on day 7 (P<0.05). In conclusion, PVE with fibrinogen and OK-432 markedly increased the CD68(+)CD163(-) infiltrating macrophages around the peri-portal area in the liver. This novel technique could be applied as immune-enhanced chemo-embolization of liver tumors. PMID:27062693

  5. Incidence of ischemic stroke and systemic embolism in patients with hypertrophic cardiomyopathy, nonvalvular atrial fibrillation, CHA2DS2-VASc score of ≤1 and without anticoagulant therapy.

    PubMed

    Yang, Yin-Jian; Yuan, Jin-Qing; Fan, Chao-Mei; Pu, Jie-Lin; Fang, Pi-Hua; Ma, Jian; Guo, Xi-Ying; Li, Yi-Shi

    2016-07-01

    Data on the risk of ischemic stroke and systemic embolism (iSSE) events in patients with nonvalvular atrial fibrillation (NVAF), a CHA2DS2-VASc score of ≤1, hypertrophic cardiomyopathy (HCM), and without anticoagulant therapy are still lacking. The aim of this study was to investigate the incidence of iSSE events in these patients. We consecutively screened medical records of patients with HCM and NVAF referred to Fuwai Hospital between January 1994 and March 2014. The primary end point was iSSE events, defined as a composite of ischemic stroke and systemic embolism. Follow-up was carried out to ascertain end point status. Medical records of 522 patients with NVAF and HCM were screened. A total of 108 patients (20.7 %) with a CHA2DS2-VASc score of ≤1 and without anticoagulant therapy were enrolled and constituted our study population. After a median follow-up of 2.4 years (range 0.6-14.1 years; 376.2 patient-years), ischemic stroke occurred in 2 patients, resulting in death of 1 patient in the first year and paralysis of the other patient in the fourth year. No other iSSE events occurred. The incidence of iSSE was 0.9 % [95 % confidence interval (CI) 0.0-5.0 %] in the first year, and 0.5 % per 100 patient-years (95 % CI 0.1-1.9 %). The risk of iSSE events seems low in patients with NVAF, a CHA2DS2-VASc score of ≤1, HCM, and without anticoagulant therapy. Multicenter studies with sizeable study populations are needed to validate the risk of iSSE events in these patients. PMID:26231425

  6. Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke.

    PubMed

    Au, Jennifer L; Weishaupt, Nina; Nell, Hayley J; Whitehead, Shawn N; Cechetto, David F

    2016-01-01

    Alzheimer's disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small unilateral striatal stroke. For a model with the combination of both stroke and AD, behavioral tests that assess stroke-related motor control, locomotion and AD-related cognitive function must be implemented. The cylinder task involves a cost-efficient, multipurpose apparatus that assesses spontaneous forelimb motor use. In this task, a rat is placed in a cylindrical apparatus, where the rat will spontaneously rear and contact the wall of the cylinder with its forelimbs. These contacts are considered forelimb motor use and quantified during video analysis after testing. Another cost-efficient motor task implemented is the beam-walk task, which assesses forelimb control, hindlimb control and locomotion. This task involves a rat walking across a wooden beam allowing for the assessment of limb motor control through analysis of forelimb slips, hindlimb slips and falls. Assessment of learning and memory is completed with Morris water maze for this behavioral paradigm. The protocol starts with spatial learning, whereby the rat locates a stationary hidden platform. After spatial learning, the platform is removed and both short-term and long-term spatial reference memory is assessed. All three of these tasks are sensitive to behavioral differences and completed within 28 days for this model, making this paradigm time-efficient and cost-efficient. PMID:27022854

  7. Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model.

    PubMed

    Allahtavakoli, Mohammad; Amin, Fatemeh; Esmaeeli-Nadimi, Ali; Shamsizadeh, Ali; Kazemi-Arababadi, Mohammad; Kennedy, Derek

    2015-11-01

    Delayed treatment of stroke with recombinant tissue plasminogen activator (r-tPA) induces overexpression of matrix metalloproteinase 9 (MMP-9) which leads to breakdown of the blood-brain barrier (BBB) and causes more injuries to the brain parenchyma. In this study, the effect of ascorbic acid (AA), an antioxidant agent, on the delayed administration of r-tPA in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated. Forty male rats were randomly divided into four groups: untreated control rats (ischaemic animals), AA-treated (500 mg/kg; 5 hr after stroke) rats, r-tPA-treated (5 hr after stroke 1 mg/kg) rats and rats treated with the combination of AA and r-tPA. Middle cerebral artery occlusion was induced by occluding the right middle cerebral artery (MCA). Infarct size, BBB, brain oedema and the levels of MMP-9 were measured at the end of study. Neurological deficits were evaluated at 24 and 48 hr after stroke. Compared to the control or r-tPA-treated animals, AA alone (p < 0.001) or in combination with r-tPA (p < 0.05) significantly decreased infarct volume. Ascorbic acid alone or r-tPA + AA significantly reduced BBB permeability (p < 0.05), levels of MMP-9 (p < 0.05 versus control; p < 0.01 versus r-tPA) and brain oedema (p < 0.001) when compared to either the control or the r-tPA-treated animals. Latency to the removal of sticky labels from the forepaw was also significantly decreased after the administration of AA + r-tPA (p < 0.05) at 24 or 48 hr after stroke. Based on our data, acute treatment with AA may be considered as a useful candidate to reduce the side effects of delayed application of r-tPA in stroke therapy. PMID:25899606

  8. Quantitative evaluation of microvascular density after stroke in rats using MRI

    PubMed Central

    Bosomtwi, Asamoah; Jiang, Quan; Ding, Guang L; Zhang, Li; Zhang, Zheng G; Lu, Mei; Ewing, James R; Chopp, Michael

    2008-01-01

    We investigated vascular changes after stroke using magnetic resonance imaging (MRI) microvascular density (MVD) measurement. T2 and T2∗ were measured in eight rats before and after injecting an intravascular superparamagnetic iron oxide contrast agent to derive the corresponding transverse relaxation shift. Reliability of MRI for measurement of MVD was compared with corresponding sections immunostained with von Willebrand factor (vWF) 2 weeks after stroke. The intracorrelation coefficient (ICC) and its 95% lower bound (LB) was high in the ischemic recovery region (ICC = 0.753), moderate in the contralateral area of normal brain tissue (ICC = 0.70), and low in the ischemic core (ICC = 0.24). A very good agreement (ICC = 0.85) and correlation (r = 0.90) were observed using only the recovery region and normal contralateral hemisphere (ICC = 0.85; 95% LB = 0.78; P < 0.05). The mean MRI MVD in the center of the core lesion (26±9 per mm2) was lower than in the recovery region (209±60 per mm2) or contralateral normal hemisphere (313±32 per mm2). However, large errors in MRI MVD were encountered in the ischemic core. Our data demonstrate that MRI MVD measurements can quantitatively evaluate microvascular changes in the brain tissue after stroke, if the MVD is not extremely low as in the ischemic core. PMID:18766197

  9. Stroke - secondary to cardiogenic embolism

    MedlinePlus Videos and Cool Tools

    A blood clot, or embolus, can form and break-off from the heart. The clot travels through the bloodstream ... the brain, blocking the flow of oxygen-rich blood. The lack of oxygen results in damage, destruction, ...

  10. Method parameters’ impact on mortality and variability in rat stroke experiments: a meta-analysis

    PubMed Central

    2013-01-01

    Background Even though more than 600 stroke treatments have been shown effective in preclinical studies, clinically proven treatment alternatives for cerebral infarction remain scarce. Amongst the reasons for the discrepancy may be methodological shortcomings, such as high mortality and outcome variability, in the preclinical studies. A common approach in animal stroke experiments is that A) focal cerebral ischemia is inflicted, B) some type of treatment is administered and C) the infarct sizes are assessed. However, within this paradigm, the researcher has to make numerous methodological decisions, including choosing rat strain and type of surgical procedure. Even though a few studies have attempted to address the questions experimentally, a lack of consensus regarding the optimal methodology remains. Methods We therefore meta-analyzed data from 502 control groups described in 346 articles to find out how rat strain, procedure for causing focal cerebral ischemia and the type of filament coating affected mortality and infarct size variability. Results The Wistar strain and intraluminal filament procedure using a silicone coated filament was found optimal in lowering infarct size variability. The direct and endothelin methods rendered lower mortality rate, whereas the embolus method increased it compared to the filament method. Conclusions The current article provides means for researchers to adjust their middle cerebral artery occlusion (MCAo) protocols to minimize infarct size variability and mortality. PMID:23548160

  11. Voluntary forced use of the impaired limb following stroke facilitates functional recovery in the rat.

    PubMed

    Livingston-Thomas, Jessica M; McGuire, Emily P; Doucette, Tracy A; Tasker, R Andrew

    2014-03-15

    Constraint induced movement therapy (CIMT), which forces use of the impaired arm following stroke, improves functional recovery. The mechanisms underlying recovery are not well understood, necessitating further investigation into how rehabilitation may affect neuroplasticity using animal models. Animal motivation and stress make modelling CIMT in animals challenging. We have shown that following focal ischemia, voluntary forced use therapy using pet activity balls could engage the impaired forelimb and result in a modest acceleration in recovery. In this study, we investigated the effects of a more intensive appetitively motivated regimen that included task specific reaching exercises. Adult male Sprague Dawley rats were subjected to focal unilateral stroke using intracerebral injections of endothelin-1 or sham surgery. Three days later, stroke animals were assigned to daily rehabilitation or control therapy. Rehabilitation consisted of 30 min of generalized movement sessions in activity balls, followed by 30 min of voluntary task-specific movement using reaching boxes. Rats were tested weekly to measure forelimb deficit and recovery. After 30 days, animals were euthanized and tissue was examined for infarct volume, brain derived neurotrophic factor expression, and the presence of new neurons using doublecortin immunohistochemistry. Rehabilitation resulted in a significant acceleration of forelimb recovery in several tests, and a significant increase in the number of doublecortin-expressing cells. Furthermore, while the proportion of cells expressing BDNF in the peri-infarct region did not change, there was a shift in the cellular origin of expressed BDNF, resulting in significantly more non-neuronal, non-astrocytic BDNF, presumed to be of microglial origin. PMID:24388978

  12. Peripheral Administration of Human Adrenomedullin and Its Binding Protein Attenuates Stroke-Induced Apoptosis and Brain Injury in Rats

    PubMed Central

    Chaung, Wayne W; Wu, Rongqian; Ji, Youxin; Wang, Zhimin; Dong, Weifeng; Cheyuo, Cletus; Qi, Lei; Qiang, Xiaoling; Wang, Haichao; Wang, Ping

    2011-01-01

    Stroke is a leading cause of death and the primary medical cause of acquired adult disability worldwide. The progressive brain injury after acute stroke is partly mediated by ischemia-elicited inflammatory responses. The vasoactive hormone adrenomedullin (AM), upregulated under various inflammatory conditions, counterbalances inflammatory responses. However, regulation of AM activity in ischemic stroke remains largely unknown. Recent studies have demonstrated the presence of a specific AM binding protein (that is, AMBP-1) in mammalian blood. AMBP-1 potentiates AM biological activities. Using a rat model of focal cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO), we found that plasma levels of AM increased significantly, whereas plasma levels of AMBP-1 decreased significantly after stroke. When given peripherally early after MCAO, exogenous human AM in combination with human AMBP-1 reduced brain infarct volume 24 and 72 h after MCAO, an effect not observed after the treatment by human AM or human AMBP-1 alone. Furthermore, treatment of human AM/AMBP-1 reduced neuron apoptosis and morphological damage, inhibited neutrophil infiltration in the brain and decreased serum levels of S100B and lactate. Thus, human AM/AMBP-1 has the ability to reduce stroke-induced brain injury in rats. AM/AMBP-1 can be developed as a novel therapeutic agent for patients with ischemic stroke. PMID:21695352

  13. Human bone marrow mesenchymal stem cell transplantation attenuates axonal injury in stroke rats

    PubMed Central

    Xu, Yi; Du, Shiwei; Yu, Xinguang; Han, Xiao; Hou, Jincai; Guo, Hao

    2014-01-01

    Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that intravenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including microtubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These findings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneficial effects include resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration. PMID:25657721

  14. Venlafaxine treatment after endothelin-1-induced cortical stroke modulates growth factor expression and reduces tissue damage in rats.

    PubMed

    Zepeda, Rodrigo; Contreras, Valentina; Pissani, Claudia; Stack, Katherine; Vargas, Macarena; Owen, Gareth I; Lazo, Oscar M; Bronfman, Francisca C

    2016-08-01

    Neuromodulators, such as antidepressants, may contribute to neuroprotection by modulating growth factor expression to exert anti-inflammatory effects and to support neuronal plasticity after stroke. Our objective was to study whether early treatment with venlafaxine, a serotonin-norepinephrine reuptake inhibitor, modulates growth factor expression and positively contributes to reducing the volume of infarcted brain tissue resulting in increased functional recovery. We studied the expression of BDNF, FGF2 and TGF-β1 by examining their mRNA and protein levels and cellular distribution using quantitative confocal microscopy at 5 days after venlafaxine treatment in control and infarcted brains. Venlafaxine treatment did not change the expression of these growth factors in sham rats. In infarcted rats, BDNF mRNA and protein levels were reduced, while the mRNA and protein levels of FGF2 and TGF-β1 were increased. Venlafaxine treatment potentiated all of the changes that were induced by cortical stroke alone. In particular, increased levels of FGF2 and TGF-β1 were observed in astrocytes at 5 days after stroke induction, and these increases were correlated with decreased astrogliosis (measured by GFAP) and increased synaptophysin immunostaining at twenty-one days after stroke in venlafaxine-treated rats. Finally, we show that venlafaxine reduced infarct volume after stroke resulting in increased functional recovery, which was measured using ladder rung motor tests, at 21 days after stroke. Our results indicate that the early oral administration of venlafaxine positively contributes to neuroprotection during the acute and late events that follow stroke. PMID:26965219

  15. Relaxin Peptide Hormones Are Protective During the Early Stages of Ischemic Stroke in Male Rats

    PubMed Central

    Willcox, Jordan M.; Alibhai, Faisal J.; Connell, Barry J.; Saleh, Tarek M.; Wilson, Brian C.; Summerlee, Alastair J. S.

    2015-01-01

    The pregnancy hormone relaxin protects tissue from ischemic damage. The ability of relaxin-3, a relaxin paralog, to do so has not been explored. The cerebral expression levels of these peptides and their receptors make them logical targets for study in the ischemic brain. We assessed relaxin peptide-mediated protection, relative relaxin family peptide receptor (RXFP) involvement, and protective mechanisms. Sprague-Dawley rats receiving permanent (pMCAO) or transient middle cerebral artery occlusions (tMCAO) were treated with relaxin peptides, and brains were collected for infarct analysis. Activation of the endothelial nitric oxide synthase pathway was evaluated as a potential protective mechanism. Primary cortical rat astrocytes were exposed to oxygen glucose deprivation and treated with relaxin peptides, and viability was examined. Receptor involvement was explored using RXFP3 antagonist or agonist treatment and real-time PCR. Relaxin and relaxin-3 reduced infarct size after pMCAO. Both peptides activated endothelial nitric oxide synthase. Because relaxin-3 has not previously been associated with this pathway and displays promiscuous RXFP binding, we explored the receptor contribution. Expression of rxfp1 was greater than that of rxfp3 in rat brain, although peptide binding at either receptor resulted in similar overall protection after pMCAO. Only RXFP3 activation reduced infarct size after tMCAO. In astrocytes, rxfp3 gene expression was greater than that of rxfp1. Selective activation of RXFP3 maintained astrocyte viability after oxygen glucose deprivation. Relaxin peptides are protective during the early stages of ischemic stroke. Differential responses among treatments and models suggest that RXFP1 and RXFP3 initiate different protective mechanisms. This preliminary work is a pivotal first step in identifying the clinical implications of relaxin peptides in ischemic stroke. PMID:25456068

  16. Relaxin peptide hormones are protective during the early stages of ischemic stroke in male rats.

    PubMed

    Bergeron, Lindsay H; Willcox, Jordan M; Alibhai, Faisal J; Connell, Barry J; Saleh, Tarek M; Wilson, Brian C; Summerlee, Alastair J S

    2015-02-01

    The pregnancy hormone relaxin protects tissue from ischemic damage. The ability of relaxin-3, a relaxin paralog, to do so has not been explored. The cerebral expression levels of these peptides and their receptors make them logical targets for study in the ischemic brain. We assessed relaxin peptide-mediated protection, relative relaxin family peptide receptor (RXFP) involvement, and protective mechanisms. Sprague-Dawley rats receiving permanent (pMCAO) or transient middle cerebral artery occlusions (tMCAO) were treated with relaxin peptides, and brains were collected for infarct analysis. Activation of the endothelial nitric oxide synthase pathway was evaluated as a potential protective mechanism. Primary cortical rat astrocytes were exposed to oxygen glucose deprivation and treated with relaxin peptides, and viability was examined. Receptor involvement was explored using RXFP3 antagonist or agonist treatment and real-time PCR. Relaxin and relaxin-3 reduced infarct size after pMCAO. Both peptides activated endothelial nitric oxide synthase. Because relaxin-3 has not previously been associated with this pathway and displays promiscuous RXFP binding, we explored the receptor contribution. Expression of rxfp1 was greater than that of rxfp3 in rat brain, although peptide binding at either receptor resulted in similar overall protection after pMCAO. Only RXFP3 activation reduced infarct size after tMCAO. In astrocytes, rxfp3 gene expression was greater than that of rxfp1. Selective activation of RXFP3 maintained astrocyte viability after oxygen glucose deprivation. Relaxin peptides are protective during the early stages of ischemic stroke. Differential responses among treatments and models suggest that RXFP1 and RXFP3 initiate different protective mechanisms. This preliminary work is a pivotal first step in identifying the clinical implications of relaxin peptides in ischemic stroke. PMID:25456068

  17. Polyhydroxylated fullerene nanoparticles attenuate brain infarction and oxidative stress in rat model of ischemic stroke

    PubMed Central

    Vani, Javad Rasouli; Mohammadi, Mohammad Taghi; Foroshani, Mahsa Sarami; Jafari, Mahvash

    2016-01-01

    Oxidative stress is the common underlying mechanism of damage in ischemic stroke. Therefore, we aimed to evaluate the possible protective effects of polyhydroxylated fullerene derivatives on brain infarction and oxidative/nitrosative stress in a rat model of ischemic stroke. The experiment was performed by four groups of rats (each; n=12); Sham, Control ischemia, and ischemic treatment groups (Pretreatment and Posttreatment). Brain ischemia was induced by 90 min middle cerebral artery occlusion (MCAO) followed by 24 hours reperfusion. Rats received fullerene nanoparticles at dose of 1 mg/kg 30 min before MCAO and immediately after beginning of reperfusion. Infarct volume, contents of malondialdehyde (MDA), glutathione (GSH) and nitrate as well as superoxide dismutase (SOD) activity were assessed 24 hours after termination of MCAO. Brain infarct volume was 310 ± 21 mm3 in control group. Administration of fullerene nanoparticles before and after MCAO significantly decreased the infarct volume by 53 % (145 ± 45 mm3) and 81 % (59 ± 13 mm3), respectively. Ischemia also enhanced MDA and nitrate contents of ischemic hemispheres by 45 % and 25 % , respectively. Fullerene nanoparticles considerably reduced the MDA and nitrate contents of ischemic hemispheres before MCAO by 58 % and 17 % , respectively, and after MCAO by 38 % and 21 % , respectively. Induction of MCAO significantly decreased GSH content (19 % ) and SOD activity (52 % ) of ischemic hemispheres, whereas fullerene nanoparticles increased the GSH content and SOD activity of ischemic hemispheres by 19 % and 52 % before MCAO, respectively, and 21 % and 55 % after MCAO, respectively. Our findings indicate that fullerene nanoparticles, as a potent scavenger of free radicals, protect the brain cells against ischemia/reperfusion injury and inhibit brain oxidative/nitrosative damage. PMID:27540350

  18. Therapeutic effects of lipo-prostaglandin E1 on angiogenesis and neurogenesis after ischemic stroke in rats.

    PubMed

    Ling, Li; Zhang, Suping; Ji, Zhangge; Huang, Huihong; Yao, Gang; Wang, Muzhen; He, Rui; Deng, Wanqing; Fang, Li

    2016-01-01

    Previous studies have demonstrated that prostaglandin E1 (PGE1) has a neuroprotective effect on cerebral ischemia. However, it remains unknown whether PGE1 promotes angiogenesis and neurogenesis after ischemic stroke. In this study, adult male Sprague-Dawley rats were subjected to permanently distal middle cerebral artery occlusion (MCAO). Rats were treated with lipo-prostaglandin E1(lipo-PGE1, 10 μg/kg/d) or the same volume of 0.9% saline starting 24 hours after MCAO daily for 6 consecutive days. All rats were injected 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg) intraperitoneally every 12 hours for 3 consecutive days before being sacrificed. At 7 and 14 days after MCAO or sham-operation, rats were sacrificed. Post-stroke neurological outcome, infarction volume, angiogenesis and neurogenesis were evaluated. Treatment with lipo-PGE1 significantly increased the vascular density in the peri-infarct areas at 7 and 14 days after MCAO. The lipo-PGE1 treatment significantly enhanced the proliferation and migration of endogenous neural stem cells in the ipsilateral subventricular zone. The neural stem cells associated with blood vessels closely within a neurovascular niche in lipo-PGE1-treated rats after stroke. The lipo-PGE1 treatment also significantly improved the neurological recovery after MCAO. These results indicate that treatment with lipo-PGE1 promotes post-stroke angiogenesis, neurogenesis and their interaction, which would contribute to neurological recovery after cerebral infarction. Our study provides novel experimental evidences for the neuroprotective roles of PGE1 in ischemic stroke. PMID:26000823

  19. Human Placenta-Derived Adherent Cell Treatment of Experimental Stroke Promotes Functional Recovery after Stroke in Young Adult and Older Rats

    PubMed Central

    Shehadah, Amjad; Chen, Jieli; Pal, Ajai; He, Shuyang; Zeitlin, Andrew; Cui, Xu; Zacharek, Alex; Cui, Yisheng; Roberts, Cynthia; Lu, Mei; Hariri, Robert; Chopp, Michael

    2014-01-01

    Background Human Placenta-Derived Adherent Cells (PDAC®) are a novel mesenchymal-like cell population derived from normal human placental tissue. PDA-001 is a clinical formulation of PDAC® developed for intravenous administration. In this study, we investigated the efficacy of PDA-001 treatment in a rat model of transient middle cerebral artery occlusion (MCAo) in young adult (2–3 month old) and older rats (10–12 months old). Methods To evaluate efficacy and determine the optimal number of transplanted cells, young adult Wistar rats were subjected to MCAo and treated 1 day post MCAo with 1×106, 4×106 or 8×106 PDA-001 cells (i.v.), vehicle or cell control. 4×106 or 8×106 PDA-001 cells were also tested in older rats after MCAo. Treatment response was evaluated using a battery of functional outcome tests, consisting of adhesive-removal test, modified Neurological Severity Score (mNSS) and foot-fault test. Young adult rats were sacrificed 56 days after MCAo, older rats were sacrificed 29 days after MCAo, and lesion volumes were measured using H&E. Immunohistochemical stainings for bromodeoxyuridine (BrdU) and von Willebrand Factor (vWF), and synaptophysin were performed. Results In young adult rats, treatment with 4×106 PDA-001 cells significantly improved functional outcome after stroke (p<0.05). In older rats, significant functional improvement was observed with PDA-001 cell therapy in both of the 4×106 and 8×106 treatment groups. Functional benefits in young adult and older rats were associated with significant increases in the number of BrdU immunoreactive endothelial cells, vascular density and perimeter in the ischemic brain, as well as significantly increased synaptophysin expression in the ischemic border zone (p<0.05). Conclusion PDA-001 treatment significantly improved functional outcome after stroke in both young adult and older rats. The neurorestorative effects induced by PDA-001 treatment may be related to increased vascular density and

  20. Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke.

    PubMed

    Lee, Ji Yong; Kim, Eiru; Choi, Seong-Mi; Kim, Dong-Wook; Kim, Kwang Pyo; Lee, Insuk; Kim, Han-Soo

    2016-01-01

    Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract-treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract-treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury. PMID:27609711

  1. Microvesicles from brain-extract—treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke

    PubMed Central

    Lee, Ji Yong; Kim, Eiru; Choi, Seong-Mi; Kim, Dong-Wook; Kim, Kwang Pyo; Lee, Insuk; Kim, Han-Soo

    2016-01-01

    Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract—treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract—treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury. PMID:27609711

  2. Metabolic properties in stroked rats revealed by relaxation-enhanced magnetic resonance spectroscopy at ultrahigh fields.

    PubMed

    Shemesh, Noam; Rosenberg, Jens T; Dumez, Jean-Nicolas; Muniz, Jose A; Grant, Samuel C; Frydman, Lucio

    2014-01-01

    (1)H magnetic resonance spectroscopy (MRS) yields site-specific signatures that directly report metabolic concentrations, biochemistry and kinetics-provided spectral sensitivity and quality are sufficient. Here, an enabling relaxation-enhanced (RE) MRS approach is demonstrated that by combining highly selective spectral excitations with operation at very high magnetic fields, delivers spectra exhibiting signal-to-noise ratios >50:1 in under 6 s for ~5 × 5 × 5 (mm)(3) voxels, with flat baselines and no interference from water. With this spectral quality, MRS was used to interrogate a number of metabolic properties in stroked rat models. Metabolic confinements imposed by randomly oriented micro-architectures were detected and found to change upon ischaemia; intensities of downfield resonances were found to be selectively altered in stroked hemispheres; and longitudinal relaxation time of lactic acid was found to increase by over 50% its control value as early as 3-h post ischaemia, paralleling the onset of cytotoxic oedema. These results demonstrate potential of (1)H MRS at ultrahigh fields. PMID:25229942

  3. Glibenclamide enhances the effects of delayed hypothermia after experimental stroke in rats.

    PubMed

    Wu, Zhou; Zhu, Shu-Zhen; Hu, Ya-Fang; Gu, Yong; Wang, Sheng-Nan; Lin, Zhen-Zhou; Xie, Zuo-Shan; Pan, Su-Yue

    2016-07-15

    In order to evaluate whether glibenclamide can extend the therapeutic window during which induced hypothermia can protect against stroke, we subjected adult male Sprague-Dawley rats to middle cerebral artery occlusion (MCAO). We first verified the protective effects of hypothermia induced at 0, 2, 4 or 6h after MCAO onset, and then we assessed the effects of the combination of glibenclamide and hypothermia at 6, 8 or 10h after MCAO onset. At 24h after MCAO, we assessed brain edema, infarct volume, modified neurological severity score, Evans Blue leakage and expression of Sulfonylurea receptor 1 (SUR1) protein and pro-inflammatory factors. No protective effects were observed when hypothermia was induced too long after MCAO. At 6h after MCAO onset, hypothermia alone failed to decrease cerebral edema and infarct volume, but the combination of glibenclamide and hypothermia decreased both. The combination also improved neurological outcome, ameliorated blood-brain barrier damage and decreased levels of COX-2, TNF-α and IL-1β. These results suggest that glibenclamide enhances and extends the therapeutic effects of delayed hypothermia against ischemia stroke, potentially by ameliorating blood-brain barrier damage and declining levels of pro-inflammatory factors. PMID:27134036

  4. Optical monitoring of stress-related changes in the brain tissues and vessels associated with hemorrhagic stroke in newborn rats.

    PubMed

    Semyachkina-Glushkovskaya, Oxana; Pavlov, Alexey; Kurths, Jürgen; Borisova, Ekaterina; Gisbrecht, Alexander; Sindeeva, Olga; Abdurashitov, Arkady; Shirokov, Alexander; Navolokin, Nikita; Zinchenko, Ekaterina; Gekalyuk, Artem; Ulanova, Maria; Zhu, Dan; Luo, Qingming; Tuchin, Valery

    2015-10-01

    Stress is a major factor for a risk of cerebrovascular catastrophes. Studying of mechanisms underlying stress-related brain-injures in neonates is crucial for development of strategy to prevent of neonatal stroke. Here, using a model of sound-stress-induced intracranial hemorrhages in newborn rats and optical methods, we found that cerebral veins are more sensitive to the deleterious effect of stress than arteries and microvessels. The development of venous insufficiency with decreased blood outflow from the brain accompanied by hypoxia, reduction of complexity of venous blood flow and high production of beta-arrestin-1 are possible mechanisms responsible for a risk of neonatal hemorrhagic stroke. PMID:26504656

  5. Pulmonary Embolism

    MedlinePlus

    ... is a sudden blockage in a lung artery. The cause is usually a blood clot in the leg called a deep vein thrombosis that breaks loose and travels through the bloodstream to the lung. Pulmonary embolism is a ...

  6. Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats.

    PubMed

    Hays, Seth A; Ruiz, Andrea; Bethea, Thelma; Khodaparast, Navid; Carmel, Jason B; Rennaker, Robert L; Kilgard, Michael P

    2016-07-01

    Advanced age is associated with a higher incidence of stroke and worse functional outcomes. Vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a potential method to improve recovery after brain injury but to date has only been evaluated in young rats. Here, we evaluated whether VNS paired with rehabilitative training would improve recovery of forelimb function after ischemic lesion of the motor cortex in rats 18 months of age. Rats were trained to perform the isometric pull task, an automated, quantitative measure of volitional forelimb strength. Once proficient, rats received an ischemic lesion of the motor cortex and underwent rehabilitative training paired with VNS for 6 weeks. VNS paired with rehabilitative training significantly enhances recovery of forelimb function after lesion. Rehabilitative training without VNS results in a 34% ± 19% recovery, whereas VNS paired with rehabilitative training yields a 98% ± 8% recovery of prelesion of forelimb function. VNS does not significantly reduce lesion size. These findings demonstrate that VNS paired with rehabilitative training enhances motor recovery in aged subjects in a model of stroke and may suggest that VNS therapy may effectively translate to elderly stroke patients. PMID:27255820

  7. Vasodilating and hypotensive effects of fangchinoline and tetrandrine on the rat aorta and the stroke-prone spontaneously hypertensive rat.

    PubMed

    Kim, H S; Zhang, Y H; Oh, K W; Ahn, H Y

    1997-10-01

    Comparative studies of the effects of tetrandrine (TET) and fangchinoline (FAN), two major components of the Radix of Stephannia tetrandrae, on vasodilations and on calcium movement in vascular smooth muscle, and studies of hypotensive effects on stroke-prone spontaneously hypertensive rats (SHRSP) were performed in the following experiments. TET and FAN inhibited high K+ (65.4 mM) and induced sustained contraction in the rat aorta smooth muscle strips. IC50 values for TET and FAN were 0.27 +/- 0.05 microM (n = 6) and 9.53 +/- 1.57 microM (n = 6), respectively, and this inhibition was antagonized by increasing the Ca2+ concentration in the medium. The IC50 of TET for norepinephrine (NE)-induced contraction (0.86 +/- 0.04 g) was 3.08 +/- 0.05 microM (n = 4), and the IC50 of FAN for NE-induced contraction (0.88 +/- 0.07 g) was 14.20 +/- 0.40 microM (n = 4). At the molecular level, radiolabelled 45Ca2+ uptake tests revealed that TET and FAN also inhibited high K+ (65.4 mM) and 1 microM NE-stimulated Ca2+ influx in rat aorta strips at the maximal concentration was needed to inhibit the contraction. TET (3 mg/kg) and FAN (30 mg/kg) administered by intravenous (i.v.) bolus injection also lowered the mean arterial pressure (MAP) significantly during the period of observation in conscious SHRSP, respectively. These results showed that TET was more potent than FAN in blocking calcium channels and antihypertensive activity. PMID:9406900

  8. Vascular reactivity in the spontaneously hypertensive stroke-prone rat. Effect of antihypertensive treatment.

    PubMed

    Soltis, E E; Bohr, D F

    1987-05-01

    This study investigated vascular responsiveness in stroke-prone spontaneously hypertensive rats (SHRSP) and the effect of antihypertensive treatment on this responsiveness. Weanling (4-week-old) male and female SHRSP and Wistar-Kyoto rats (WKY) received either the antihypertensive combination treatment of hydralazine plus hydrochlorothiazide in drinking water or tap water alone (controls) for 15 weeks. Whereas the antihypertensive combination prevented the development of hypertension in treated SHRSP (SHRSP-T), blood pressure remained unchanged in treated WKY (WKY-T). Femoral arterial smooth muscle responsiveness to KCl, norepinephrine, and calcium (in the presence of either 40 mM KCl or 1 microM norepinephrine) was not altered in SHRSP when compared with WKY. A significant increase in the sensitivity of femoral arteries to KCl and calcium (in the presence of 40 mM KCl) was seen, however, in SHRSP-T and WKY-T. An increased sensitivity to norepinephrine and calcium (in the presence of 1 microM norepinephrine) was seen only in SHRSP-T. Isoproterenol-induced relaxation was significantly attenuated in both SHRSP and SHRSP-T. Relaxation induced by sodium nitroprusside and calcium (membrane stabilization) was not different between the four groups. These results show that femoral arterial smooth muscle responsiveness to vasoconstrictor stimuli is not altered in SHRSP but that beta-adrenergic-mediated relaxation is attenuated. Antihypertensive treatment resulted in an enhanced responsiveness to these vasoconstrictor stimuli but had no effect on the relaxation properties of femoral arterial smooth muscle. PMID:3570424

  9. Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage

    PubMed Central

    Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.

    2014-01-01

    Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730

  10. Laser system refinements to reduce variability in infarct size in the rat photothrombotic stroke model

    PubMed Central

    Alaverdashvili, Mariam; Paterson, Phyllis G.; Bradley, Michael P.

    2015-01-01

    Background The rat photothrombotic stroke model can induce brain infarcts with reasonable biological variability. Nevertheless, we observed unexplained high inter-individual variability despite using a rigorous protocol. Of the three major determinants of infarct volume, photosensitive dye concentration and illumination period were strictly controlled, whereas undetected fluctuation in laser power output was suspected to account for the variability. New method The frequently utilized Diode Pumped Solid State (DPSS) lasers emitting 532 nm (green) light can exhibit fluctuations in output power due to temperature and input power alterations. The polarization properties of the Nd:YAG and Nd:YVO4 crystals commonly used in these lasers are another potential source of fluctuation, since one means of controlling output power uses a polarizer with a variable transmission axis. Thus, the properties of DPSS lasers and the relationship between power output and infarct size were explored. Results DPSS laser beam intensity showed considerable variation. Either a polarizer or a variable neutral density filter allowed adjustment of a polarized laser beam to the desired intensity. When the beam was unpolarized, the experimenter was restricted to using a variable neutral density filter. Comparison with existing method(s) Our refined approach includes continuous monitoring of DPSS laser intensity via beam sampling using a pellicle beamsplitter and photodiode sensor. This guarantees the desired beam intensity at the targeted brain area during stroke induction, with the intensity controlled either through a polarizer or variable neutral density filter. Conclusions Continuous monitoring and control of laser beam intensity is critical for ensuring consistent infarct size. PMID:25840363

  11. Study of the Efficacy, Safety and Tolerability of Low-Molecular-Weight Heparin vs. Unfractionated Heparin as Bridging Therapy in Patients with Embolic Stroke due to Atrial Fibrillation

    PubMed Central

    Feiz, Farnia; Sedghi, Reyhane; Salehi, Alireza; Hatam, Nahid; Bahmei, Jamshid; Borhani-Haghighi, Afshin

    2016-01-01

    Background Anticoagulation with adjusted dose warfarin is a well-accepted treatment for the prevention of recurrent stroke in patients with atrial fibrillation. Meanwhile, using bridging therapy with heparin or heparinoids before warfarin for initiation of anticoagulation is a matter of debate. We compared safety, efficacy, and tolerability of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) as a bridging method in patients with recent ischemic stroke due to atrial fibrillation. Method This study was a randomized single-blind controlled trial in patients with acute ischemic stroke due to atrial fibrillation who were eligible for receiving warfarin and were randomly treated with 60 milligrams (mg) of LMWH (enoxaparin) subcutaneously every 12 h, or 1000 units/h of continuous intravenous heparin. The primary efficacy endpoints were recurrence of new ischemic stroke, myocardial infarction and/or death. The primary safety endpoint was central nervous system and/or systemic bleeding. Results Seventy-four subjects were recruited. Baseline demographic and clinical characteristics of two groups were matched. Composite endpoint outcome of new ischemic stroke, myocardial infarction, and/or death in follow-up period was seen in 10 subjects (27.03%) in UFH group and in four subjects (10.81%) in LMWH group (p value: 0.136). All hemorrhages and symptomatic central nervous system (CNS) hemorrhages in follow-up period were in 7 (18.9%) and 4 (10.8%) patients in UFH group, in 5 (13.5%), and 3 (8.1%) patients in LMWH group (p values: 0.754 and 0.751), respectively. Drop out and major adverse-effects such as heparin-induced thrombocytopenia and drug hypersensitivity were not seen in any patient. Conclusion Enoxaparin can be a safe and efficient alternative for UFH as bridging therapy. PMID:27403222

  12. Pulse pressure variation does not reflect stroke volume variation in mechanically ventilated rats with lipopolysaccharide-induced pneumonia.

    PubMed

    Cherpanath, Thomas G V; Smeding, Lonneke; Lagrand, Wim K; Hirsch, Alexander; Schultz, Marcus J; Groeneveld, Johan A B

    2014-01-01

    1. The present study examined the relationship between centrally measured stroke volume variation (SVV) and peripherally derived pulse pressure variation (PPV) in the setting of increased total arterial compliance (CA rt ). 2. Ten male Wistar rats were anaesthetized, paralysed and mechanically ventilated before being randomized to receive intrapulmonary lipopolysaccharide (LPS) or no LPS. Pulse pressure (PP) was derived from the left carotid artery, whereas stroke volume (SV) was measured directly in the left ventricle. Values of SVV and PPV were calculated over three breaths. Balloon inflation of a catheter positioned in the inferior vena cava was used, for a maximum of 30 s, to decrease preload while the SVV and PPV measurements were repeated. Values of CA rt were calculated as SV/PP. 3. Intrapulmonary LPS increased CA rt and SV. Values of SVV and PPV increased in both LPS-treated and untreated rats during balloon inflation. There was a correlation between SVV and PPV in untreated rats before (r = 0.55; P = 0.005) and during (r = 0.69; P < 0.001) occlusion of the vena cava. There was no such correlation in LPS-treated rats either before (r = -0.08; P = 0.70) or during (r = 0.36; P = 0.08) vena cava occlusion. 4. In conclusion, under normovolaemic and hypovolaemic conditions, PPV does not reflect SVV during an increase in CA rt following LPS-induced pneumonia in mechanically ventilated rats. Our data caution against their interchangeability in human sepsis. PMID:24372424

  13. Pulmonary embolism

    SciTech Connect

    Dunnick, N.R.; Newman, G.E.; Perlmutt, L.M.; Braun, S.D.

    1988-11-01

    Pulmonary embolism is a common medical problem whose incidence is likely to increase in our aging population. Although it is life-threatening, effective therapy exists. The treatment is not, however, without significant complications. Thus, accurate diagnosis is important. Unfortunately, the clinical manifestations of pulmonary embolism are nonspecific. Furthermore, in many patients the symptoms of an acute embolism are superimposed on underlying chronic heart or lung disease. Thus, a high index of suspicion is needed to identify pulmonary emboli. Laboratory parameters, including arterial oxygen tensions and electrocardiography, are as nonspecific as the clinical signs. They may be more useful in excluding another process than in diagnosing pulmonary embolism. The first radiologic examination is the chest radiograph, but the clinical symptoms are frequently out of proportion to the findings on the chest films. Classic manifestations of pulmonary embolism on the chest radiograph include a wedge-shaped peripheral opacity and a segmental or lobar diminution in vascularity with prominent central arteries. However, these findings are not commonly seen and, even when present, are not specific. Even less specific findings include cardiomegaly, pulmonary infiltrate, elevation of a hemidiaphragm, and pleural effusion. Many patients with pulmonary embolism may have a normal chest radiograph. The chest radiograph is essential, however, for two purposes. First, it may identify another cause of the patient's symptoms, such as a rib fracture, dissecting aortic aneurysm, or pneumothorax. Second, a chest radiograph is essential to interpretation of the radionuclide V/Q scan. The perfusion scan accurately reflects the perfusion of the lung. However, a perfusion defect may result from a variety of etiologies. Any process such as vascular stenosis or compression by tumor may restrict blood flow. 84 references.

  14. Salvianolic acid B attenuates apoptosis and inflammation via SIRT1 activation in experimental stroke rats.

    PubMed

    Lv, Hongdi; Wang, Ling; Shen, Jinchang; Hao, Shaojun; Ming, Aimin; Wang, Xidong; Su, Feng; Zhang, Zhengchen

    2015-06-01

    Silent information regulator 1 (SIRT1), a histone deacetylase, has been suggested to be effective in ischemic brain diseases. Salvianolic acid B (SalB) is a polyphenolic and one of the active components of Salvia miltiorrhiza Bunge. Previous studies suggested that SalB is protective against ischemic stroke. However, the role of SIRT1 in the protective effect of SalB against cerebral ischemia has not been explored. In this study, the rat brain was subjected to middle cerebral artery occlusion (MCAO). Before this surgery, rats were intraperitoneally administrated SalB with or without EX527, a specific SIRT1 inhibitor. The infarct volume, neurological score and brain water content were assessed. In addition, levels of TNF-α and IL-1β in the brain tissues were detected by commercial ELISA kits. And the expression levels of SIRT, Ac-FOXO1, Bcl-2 and Bax were detected by Western blot. The results suggested that SalB exerted a cerebral-protective effect, as shown by reduced infarct volume, lowered brain edema and increased neurological scores. SalB also exerted anti-inflammatory effects as indicated by the decreased TNF-α and IL-1β levels in the brain tissue. Moreover, SalB upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of Ac-FOXO1 and Bax. These effects of SalB were abolished by EX527 treatment. In summary, our results demonstrate that SalB treatment attenuates brain injury induced by ischemic stoke via reducing apoptosis and inflammation through the activation of SIRT1 signaling. PMID:25981395

  15. Potassium channel antagonists and vascular reactivity in stroke-prone spontaneously hypertensive rats.

    PubMed

    Kolias, T J; Chai, S; Webb, R C

    1993-06-01

    The goal of this study was to characterize differences in contractile responsiveness to several potassium channel antagonists in vascular smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY). Helically-cut strips of carotid arteries (endothelium removed) from SHRSP and WKY were mounted in muscle baths for measurement of isometric force generation. Contractile responses to tetraethylammonium (10(-4) to 3 x 10(-2) mol/L) and barium (3 x 10(-5) mol/L), blockers of the voltage-dependent and large conductance, calcium activated potassium channels, were greater in carotid arteries from SHRSP than in those from WKY. In contrast, contractile responses to the voltage-dependent potassium channel blockers 3,4-diamino-pyridine (10(-6) to 3 x 10(-3) mol/L) and sparteine (10(-6) to 3 x 10(-2) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid arteries from SHRSP and WKY did not contract to apamin (10(-9) to 10(-6) mol/L), an antagonist of the small conductance, calcium activated potassium channel. Furthermore, relaxation responses to diazoxide (3 x 10(-4) mol/L), an activator of the ATP-sensitive potassium channel, and subsequent contractions to the ATP-sensitive potassium channel blocker glyburide (10(-8) to 3 x 10(-6) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid artery segments from SHRSP were more sensitive to the contractile effects of elevated potassium than those from WKY. We conclude that altered activity of the large conductance, calcium activated potassium channel may play a role in the increased responsiveness observed in arteries from SHRSP. PMID:8343237

  16. Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

    PubMed Central

    Campos-Martorell, Mireia; Cano-Sarabia, Mary; Simats, Alba; Hernández-Guillamon, Mar; Rosell, Anna; Maspoch, Daniel; Montaner, Joan

    2016-01-01

    Background and aims Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. Materials and methods In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt) surgery and treated (intravenous [IV]) with fluorescent-labeled liposomes with different net surface charges. Ninety minutes after the administration of liposomes, the brain, blood, liver, lungs, spleen, and kidneys were evaluated ex vivo using the Xenogen IVIS® Spectrum imaging system to detect the load of fluorescent liposomes. In a second substudy, simvastatin was assessed upon reaching the brain, comparing free and encapsulated simvastatin (IV) administration. For this purpose, simvastatin levels in brain homogenates from sham or MCAOt rats at 2 hours or 4 hours after receiving the treatment were detected through ultra-high-protein liquid chromatography. Results Whereas positively charged liposomes were not detected in brain or plasma 90 minutes after their administration, neutral and negatively charged liposomes were able to reach the brain and accumulate specifically in the infarcted area. Moreover, neutral liposomes exhibited higher bioavailability in plasma 4 hours after being administered. The detection of simvastatin by ultra-high-protein liquid chromatography confirmed its ability to cross the blood–brain barrier, when administered either as a free drug or encapsulated into liposomes. Conclusion This study confirms that liposome charge is critical to promote its accumulation in the brain infarct after MCAOt. Furthermore, simvastatin can be delivered after being encapsulated. Thus, simvastatin encapsulation might be a promising

  17. Role of echocardiography in patients with stroke.

    PubMed

    Nakanishi, Koki; Homma, Shunichi

    2016-08-01

    Investigation of potential embolic source is an important diagnostic step in treating patients with ischemic stroke and transient ischemic attack. Cardiogenic embolism has been estimated to be the causative factor in 15-30% of all cases of ischemic stroke. Cardioembolic strokes are generally severe and recurrence and mortality rate high. Various cardiac disorders including atrial fibrillation, ventricular thrombus, valvular heart disease, cardiac tumors, and structural heart defects can cause cardioembolic stroke. Although the aortic arch is not a cardiac structure, it is usually considered under source of cardiac embolism (cardioaortic source) and is reviewed in this article. Echocardiography (both transthoracic and transesophageal) is a widely used and versatile technique that can provide comprehensive information of thromboembolic risk in patients with stroke. This article reviews potential cardiac sources of stroke and discusses the role of echocardiography in clinical practice. PMID:27256218

  18. Do different reperfusion methods affect the outcomes of stroke induced by MCAO in adult rats?

    PubMed

    Zuo, Xia-Lin; Deng, Hou-Liang; Wu, Ping; Xu, En

    2016-09-01

    There are two patterns of ischemia/reperfusion (I/R) models used in rat middle cerebral artery occlusion (MCAO) I/R models, which differ in the use of unilateral or bilateral carotid artery reperfusion. The primary difference between the two patterns of I/R models is the complexity of the surgery procedure. However, researchers in this field have no idea whether there are any differences in outcomes of these two methods. In this study, we investigated the effects of the two methods on neurological deficits, infarct volume, blood-brain barrier (BBB) integrity and brain derived neurotrophic factor (BDNF) expression. Through evaluating the current way of bilateral common carotid artery reperfusion, we tried to find whether it could be replaced by an easier way. We found that there were no statistical significant differences between the different methods in infarct volume, neurological deficits, BBB integrity, and the level of BDNF (P > 0.05). These data demonstrated that different methods did not affect the neurological deficits, infarct volume, BBB integrity, and the BDNF protein level, which provides reference when we use an experimental stroke. These results suggest that the two methods have similar capability for inducing cerebral I/R injury and can be interchanged. PMID:26268737

  19. Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats

    PubMed Central

    Rodrigues, Cecilia M. P.; Solá, Susana; Nan, Zhenhong; Castro, Rui E.; Ribeiro, Paulo S.; Low, Walter C.; Steer, Clifford J.

    2003-01-01

    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 ≈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-κB activity. In addition to its protective action at the mitochondrial membrane, TUDCA also activated the Akt-1/protein kinase Bα 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:12721362

  20. Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats.

    PubMed

    Chen, Xin-ran; Liao, Song-jie; Ye, Lan-xiang; Gong, Qiong; Ding, Qiao; Zeng, Jin-sheng; Yu, Jian

    2014-01-16

    Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction. PMID:24326094

  1. Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats

    PubMed Central

    Ma, Jianhua; Zhang, Maoying; Li, Shaowu; Wu, Bingshan; Nie, Xiaohu; Jiao, Jiao; Zhao, Hao; Wang, Shanshan; Yang, Yuanyuan; Zhang, Yesen; Sun, Yilin; Wicha, Max S.; Chang, Alfred E.; Gao, Shaorong; Li, Qiao; Xu, Ruxiang

    2015-01-01

    Induced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oct4, Sox2, Klf4, c-Mycin mouse embryonic fibroblasts. They expanded readily in vitro and expressed NSC mRNA profile and protein markers. These iNSCs differentiated into mature astrocytes, neurons and oligodendrocytes in vitro. Importantly, they reduced lesion size, promoted the recovery of motor and sensory function as well as metabolism status in middle cerebral artery stroke rats. These iNSCs secreted nerve growth factors, which was associated with observed protection of neurons from apoptosis. Furthermore, iNSCs migrated to and passed through the lesion in the cerebral cortex, where Tuj1+ neurons were detected. These findings have revealed the function of transdifferentiated iNSCs in vivo, and thus provide experimental evidence to support the development of personalized regenerative therapy for CNS diseases by using genetically engineered autologous somatic cells. PMID:26352672

  2. Structure and hypotensive activity relationships of tetrandrine derivatives in stroke-prone spontaneously hypertensive rats.

    PubMed

    Kawashima, K; Hayakawa, T; Miwa, Y; Oohata, H; Suzuki, T; Fujimoto, K; Ogino, T; Chen, Z X

    1990-01-01

    1. Structure and hypotensive activity relationships of tetrandrine (TD), an alkaloid isolated from the Chinese herb Radix stephaniae tetrandrae and its derivatives were investigated in conscious stroke-prone spontaneously hypertensive rats (SHRSP). 2. Derivatives substituted at the 7-O position with various types of alkyl group produced varying degrees of hypotensive effect. 3. While the demethylated derivative, fangchinoline (FC), and its acetylated compound had no effect on blood pressure, 7-O-methyl FC (TD), and 7-O-ethyl and 7-O-isopropyl FC at oral doses of 25 and 50 mg/kg produced a gradual and sustained hypotensive effect without any significant effects on heart rate and plasma renin concentration. 4. Substitution at the 7-O position with longer side chains such as n-propyl, n-butyl and n-pentyl groups reduced both the degree and duration of hypotensive activity. 5. Substitution of N-methyl groups at the 2 and 2' positions with quaternary ammonium or N-oxide attenuated the hypotensive activity. 6. The results of this study suggest a possibility that 7-O-ethyl and 7-O-isopropyl derivatives as well as TD can be considered as potential antihypertensive drugs because of the gradual onset and long duration of their hypotensive action in SHRSP. PMID:2187737

  3. Effects of osthol on blood pressure and lipid metabolism in stroke-prone spontaneously hypertensive rats.

    PubMed

    Ogawa, Hiroshi; Sasai, Noriko; Kamisako, Toshinori; Baba, Kimiye

    2007-05-30

    Osthol, a coumarin compound, was isolated from the dried fruits of Cnidium monnieri (Umbelliferae) and the effect of dietary osthol on hypertension and lipid metabolism was examined in stroke-prone spontaneously hypertensive rats (SHRSP). Six-week-old male SHRSP were fed the experimental diet containing 0.05% osthol by weight for 4 weeks with free access to the diet and water. Elevation of systolic blood pressure was significantly suppressed on and after 3 weeks. In addition, significant decreases in cholesterol and triglyceride contents in the liver were recognized without any significant changes in serum lipids profiles. A comparative study on hepatic mRNA expression indicated that osthol induced a significant increase in 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase mRNA expression, which may lead to decrease in hepatic cholesterol pool through inhibition of the enzyme activity. Moreover, osthol induced a significant increase in acyl-CoA oxidase mRNA expression associated with an increase in carnitine palmitoyl transferase 1a mRNA expression, which suggests the acceleration of beta-oxidation of hepatic fatty acids. This may be responsible, at least in part, for the reduction of hepatic triglyceride content in SHRSP. These beneficial effects of osthol could be useful for both prevention of atherosclerosis and suppression of hepatic lipid accumulation. PMID:17324541

  4. Comparative health effects of margarines fortified with plant sterols and stanols on a rat model for hemorrhagic stroke.

    PubMed

    Ratnayake, W M N; Plouffe, L; L'Abbé, M R; Trick, K; Mueller, R; Hayward, S

    2003-12-01

    There is increased acceptance of fortifying habitual foods with plant sterols and their saturated derivatives, stanols, at levels that are considered safe. These sterols and stanols are recognized as potentially effective dietary components for lowering plasma total and LDL cholesterol. Our previous studies have shown that daily consumption of plant sterols promotes strokes and shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats. These studies question the safety of plant sterol additives. The present study was performed to determine whether a large intake of plant stanols would cause nutritional effects similar to those seen with plant sterols in SHRSP rats. Young SHRSP rats (aged 26-29 d) were fed semipurified diets containing commercial margarines fortified with either plant stanols (1.1 g/100 g diet) or plant sterols (1.4 g/100 g diet). A reference group of SHRSP rats was fed a soybean oil diet (0.02 g plant sterols/100 g diet and no plant stanols). Compared to soybean oil, both plant stanol and plant sterol margarines significantly (P < 0.05) reduced the life span of SHRSP rats. At the initial stages of feeding, there was no difference in the survival rates between the two margarine groups, but after approximately 50 d of feeding, the plant stanol group had a slightly, but significantly (P < 0.05), lower survival rate. Blood and tissue (plasma, red blood cells, liver, and kidney) concentrations of plant sterols in the plant sterol margarine group were three to four times higher than the corresponding tissue concentrations of plant stanols in the plant stanol group. The deformability of red blood cells and the platelet count of SHRSP rats fed the plant sterol margarine were significantly (P < 0.05) lower than those of the plant stanol margarine and soybean oil groups at the end of the study. These parameters did not differ between the soybean oil and plant stanol margarine groups. These results suggest that, at the levels tested in

  5. Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

    PubMed

    Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F

    2014-08-22

    Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate. PMID:24907601

  6. Beneficial Effects of Antecedent Exercise Training on Limb Motor Function and Calpain Expression in a Rat Model of Stroke

    PubMed Central

    Heo, Myoung; Kim, Eunjung

    2013-01-01

    [Purpose] In the present study, we investigated the effects of antecedent exercise on functional recovery and calpain protein expression following focal cerebral ischemia injury. [Subjects and Methods] The rat middle cerebral artery occlusion model was employed. Adult male Sprague-Dawley rats were randomly divided into 4 groups. Group I comprised untreated normal rats (n=10); Group II comprised untreated rats with focal cerebral ischemia (n=10); Group III comprised rats that performed treadmill exercise (20 m/min) training after focal cerebral ischemia (n=10); and Group IV comprised rats that performed antecedent treadmill exercise (20 m/min) training before focal cerebral ischemia (n=10). At different time points (1, 7, 14, and 21 days), limb placement test score and the levels of calpain protein in the hippocampus were examined. [Results] In the antecedent exercise group, improvements in the motor behavior index (limb placement test) were observed and hippocampal calpain protein levels were decreased. [Conclusion] These results indicated that antecedent treadmill exercise prior to focal cerebral ischemia exerted neuroprotective effects against ischemic brain injury by improving motor performance and decreasing the levels of calpain expression. Furthermore, these results suggest that antecedent treadmill exercise of an appropriate intensity is critical for post-stroke rehabilitation. PMID:24259890

  7. Abnormal uterine artery remodelling in the stroke prone spontaneously hypertensive rat

    PubMed Central

    Small, Heather Y.; Morgan, Hannah; Beattie, Elisabeth; Griffin, Sinead; Indahl, Marie; Delles, Christian; Graham, Delyth

    2016-01-01

    Introduction The stroke prone spontaneously hypertensive rat (SHRSP) is an established model of human cardiovascular risk. We sought to characterise the uteroplacental vascular response to pregnancy in this model and determine whether this is affected by the pre-existing maternal hypertension. Methods Doppler ultrasound and myography were utilised to assess uterine artery functional and structural changes pre-pregnancy and at gestational day 18 in SHRSP (untreated and nifedipine treated) and in the normotensive Wistar-Kyoto (WKY) rat. Maternal adaptations to pregnancy were also assessed along with histology and expression of genes involved in oxidative stress in the placenta. Results SHRSP uterine arteries had a pulsatile blood flow and were significantly smaller (70906 ± 3903 μm2 vs. 95656 ± 8524 μm2 cross-sectional area; p < 0.01), had a significant increase in contractile response (57.3 ± 10.5 kPa vs 27.7 ± 1.9 kPa; p < 0.01) and exhibited impaired endothelium-dependent vasorelaxation (58.0 ± 5.9% vs 13.9 ± 4.6%; p < 0.01) compared to WKY. Despite significant blood pressure lowering, nifedipine did not improve uterine artery remodelling, function or blood flow in SHRSP. Maternal plasma sFLT-1/PlGF ratio (5.3 ± 0.3 vs 4.6 ± 0.1; p < 0.01) and the urinary albumin/creatinine ratio (1.9 ± 0.2 vs 0.6 ± 0.1; p < 0.01) was increased in SHRSP vs WKY. The SHRSP placenta had a significant reduction in glycogen cell content and an increase in Hif1α, Sod1 and Vegf. Discussion We conclude that the SHRSP exhibits a number of promising characteristics as a model of spontaneous deficient uteroplacental remodelling that adversely affect pregnancy outcome, independent of pre-existing hypertension. PMID:26612342

  8. Electroacupuncture attenuates cervical spinal cord injury following cerebral ischemia/reperfusion in stroke-prone renovascular hypertensive rats

    PubMed Central

    TAN, FENG; CHEN, JIE; LIANG, YANGUI; GU, MINHUA; LI, YANPING; WANG, XUEWEN; MENG, DI

    2014-01-01

    Cerebral ischemia induces injury, not only in the ischemic core and surrounding penumbra tissues, but also in remote areas such as the cervical spinal cord. The aim of the present study was to determine the effects of electroacupuncture (EA) on cervical spinal cord injury following cerebral ischemia/reperfusion in stroke-prone renovascular hypertensive (RHRSP) rats. The results demonstrated that neuronal loss, which was assayed by Nissl staining in the cervical spinal cords of RHRSP rats subjected to transient middle cerebral artery occlusion (MCAO), was markedly decreased by EA stimulation at the GV20 (Baihui) and GV14 (Dazhui) acupoints compared with that in rats undergoing sham stimulation. Quantitative polymerase chain reaction and western blot analysis demonstrated that EA stimulation blocked the MCAO-induced elevated protein expression levels of glial fibrillary acidic protein and amyloid precursor protein in the cervical spinal cord at days 24 and 48. To further investigate the mechanism underlying the neuroprotective role of EA stimulation, the protein expression levels of Nogo-A and Nogo-66 receptor-1 (NgR1), two key regulatory molecules for neurite growth, were recorded in each group. The results revealed that EA stimulation reduced the MCAO-induced elevation of Nogo-A and NgR1 protein levels at day 14 and 28 in RHRSP rats. Therefore, the results demonstrated that EA reduced cervical spinal cord injury following cerebral ischemia in RHRSP rats, indicating that EA has the potential to be developed as a therapeutic treatment agent for cervical spinal cord injury following stroke. PMID:24926338

  9. Up-regulation of serotonin receptor 2B mRNA and protein in the peri-infarcted area of aged rats and stroke patients.

    PubMed

    Buga, Ana-Maria; Ciobanu, Ovidiu; Bădescu, George Mihai; Bogdan, Catalin; Weston, Ria; Slevin, Mark; Di Napoli, Mario; Popa-Wagner, Aurel

    2016-04-01

    Despite the fact that a high proportion of elderly stroke patients develop mood disorders, the mechanisms underlying late-onset neuropsychiatric and neurocognitive symptoms have so far received little attention in the field of neurobiology. In rodents, aged animals display depressive symptoms following stroke, whereas young animals recover fairly well. This finding has prompted us to investigate the expression of serotonin receptors 2A and 2B, which are directly linked to depression, in the brains of aged and young rats following stroke. Although the development of the infarct was more rapid in aged rats in the first 3 days after stroke, by day 14 the cortical infarcts were similar in size in both age groups i.e. 45% of total cortical volume in young rats and 55.7% in aged rats. We also found that the expression of serotonin receptor type B mRNA was markedly increased in the perilesional area of aged rats as compared to the younger counterparts. Furthermore, histologically, HTR2B protein expression in degenerating neurons was closely associated with activated microglia both in aged rats and human subjects. Treatment with fluoxetine attenuated the expression of Htr2B mRNA, stimulated post-stroke neurogenesis in the subventricular zone and was associated with an improved anhedonic behavior and an increased activity in the forced swim test in aged animals. We hypothesize that HTR2B expression in the infarcted territory may render degenerating neurons susceptible to attack by activated microglia and thus aggravate the consequences of stroke. PMID:27013593

  10. Up-regulation of serotonin receptor 2B mRNA and protein in the peri-infarcted area of aged rats and stroke patients

    PubMed Central

    Bădescu, George Mihai; Bogdan, Catalin; Weston, Ria; Slevin, Mark; Di Napoli, Mario; Popa-Wagner, Aurel

    2016-01-01

    Despite the fact that a high proportion of elderly stroke patients develop mood disorders, the mechanisms underlying late-onset neuropsychiatric and neurocognitive symptoms have so far received little attention in the field of neurobiology. In rodents, aged animals display depressive symptoms following stroke, whereas young animals recover fairly well. This finding has prompted us to investigate the expression of serotonin receptors 2A and 2B, which are directly linked to depression, in the brains of aged and young rats following stroke. Although the development of the infarct was more rapid in aged rats in the first 3 days after stroke, by day 14 the cortical infarcts were similar in size in both age groups i.e. 45% of total cortical volume in young rats and 55.7% in aged rats. We also found that the expression of serotonin receptor type B mRNA was markedly increased in the perilesional area of aged rats as compared to the younger counterparts. Furthermore, histologically, HTR2B protein expression in degenerating neurons was closely associated with activated microglia both in aged rats and human subjects. Treatment with fluoxetine attenuated the expression of Htr2B mRNA, stimulated post-stroke neurogenesis in the subventricular zone and was associated with an improved anhedonic behavior and an increased activity in the forced swim test in aged animals. We hypothesize that HTR2B expression in the infarcted territory may render degenerating neurons susceptible to attack by activated microglia and thus aggravate the consequences of stroke. PMID:27013593

  11. Increased Expression of Simple Ganglioside Species GM2 and GM3 Detected by MALDI Imaging Mass Spectrometry in a Combined Rat Model of Aβ Toxicity and Stroke

    PubMed Central

    Caughlin, Sarah; Hepburn, Jeffrey D.; Park, Dae Hee; Jurcic, Kristina; Yeung, Ken K.-C.; Cechetto, David F.; Whitehead, Shawn N.

    2015-01-01

    The aging brain is often characterized by the presence of multiple comorbidities resulting in synergistic damaging effects in the brain as demonstrated through the interaction of Alzheimer’s disease (AD) and stroke. Gangliosides, a family of membrane lipids enriched in the central nervous system, may have a mechanistic role in mediating the brain’s response to injury as their expression is altered in a number of disease and injury states. Matrix-Assisted Laser Desorption Ionization (MALDI) Imaging Mass Spectrometry (IMS) was used to study the expression of A-series ganglioside species GD1a, GM1, GM2, and GM3 to determine alteration of their expression profiles in the presence of beta-amyloid (Aβ) toxicity in addition to ischemic injury. To model a stroke, rats received a unilateral striatal injection of endothelin-1 (ET-1) (stroke alone group). To model Aβ toxicity, rats received intracerebralventricular (icv) injections of the toxic 25-35 fragment of the Aβ peptide (Aβ alone group). To model the combination of Aβ toxicity with stroke, rats received both the unilateral ET-1 injection and the bilateral icv injections of Aβ₂₅₋₃₅ (combined Aβ/ET-1 group). By 3 d, a significant increase in the simple ganglioside species GM2 was observed in the ischemic brain region of rats who received a stroke (ET-1), with or without Aβ. By 21 d, GM2 levels only remained elevated in the combined Aβ/ET-1 group. GM3 levels however demonstrated a different pattern of expression. By 3 d GM3 was elevated in the ischemic brain region only in the combined Aβ/ET-1 group. By 21 d, GM3 was elevated in the ischemic brain region in both stroke alone and Aβ/ET-1 groups. Overall, results indicate that the accumulation of simple ganglioside species GM2 and GM3 may be indicative of a mechanism of interaction between AD and stroke. PMID:26086081

  12. [Pulmonary embolism].

    PubMed

    Söffker, Gerold; Kluge, Stefan

    2015-01-01

    Acute pulmonary embolism is an important differential diagnosis of acute chest pain. The clinical signs are often non-specific. However, diagnosis and therapy must be done quickly in order to reduce morbidity and mortality. The new (2014) European guidelines for acute pulmonary embolism (PE) focus on risk-adapted diagnostic algorithms and prognosis adapted therapy concepts. According to the hemodynamic presentation the division in a high-risk group (unstable patient with persistent hypotension or shock) or in non-high-risk groups (hemodynamically stable) was proposed. In the high-risk group the immediate diagnosis is usually done by multidetector spiral computed tomography (MDCT) and primarily the medical therapy of right ventricular dysfunction and thrombolysis is recommended.In the non-high-risk group, this is subdivided into an intermediate-risk group and low-risk group, the diagnosis algorithm based on the PE-pretest probability--determined by validated scores. Moreover, the diagnosis is usually secured by MDCT--the new gold standard in the PE-diagnosis, scores, or it can be primarily ruled out due to the high negative predictive value of D-dimer determination. To improve the prognostic risk stratification in non-high-risk group patients the additional detection of right ventricular dysfunction (MDCT, echocardiography), cardiac biomarkers (troponin, NT proBNP) and validated scores (e.g. Pulmonary Embolism Severity Index) is recommended. Therefore, the intermediate-risk group can be further subdivided. For treatment of non-high-risk group patients, the initial anticoagulation (except those with severe renal insufficiency) using low molecular weight heparin/fondaparinux and conversion to vitamin-K antagonists or alternatively with direct oral anticoagulants (DOAK) is recommended. Hemodynamically stable patients with right ventricular dysfunction and myocardial ischemia (Intermediate-high-risk group patients) but with clinically progressive hemodynamic

  13. Protective Effects of Salidroside on Mitochondrial Functions against Exertional Heat Stroke-Induced Organ Damage in the Rat

    PubMed Central

    Zhang, Wei; Peng, Ming; Yang, Yang; Xiao, Zhangwu; Song, Bin; Lin, Zhaofen

    2015-01-01

    Exertional heat stroke (EHS) results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality. The present study was designed to evaluate the protective effects of salidroside on EHS by improving mitochondrial functions in the rat model. Liver and heart mitochondria were observed by transmission electron microscopy and mitochondrial membrane potential (ΔΨm) was detected by a fluorescent probe. Intramitochondrial free Ca2+ concentration, mitochondrial respiratory control ratio (RCR), reactive oxygen species (ROS) levels, superoxide dismutase (SOD), and malondialdehyde (MDA) activity were detected by the corresponding kits. RT-PCR was performed to estimate peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and manganese form of SOD (MnSOD) mRNA expression. The results demonstrated that salidroside was able to relieve EHS damage by reducing the swelling of mitochondria, ROS levels, and MDA activity, as well as increasing ΔΨm, RCR, free Ca2+ concentration, SOD, PGC-1α, and MnSOD mRNA levels. In conclusion, salidroside has protective effects on mitochondrial functions against exertional heat stroke-induced organ damage in the rat. PMID:26664452

  14. MRI detects brain reorganization after human umbilical tissue-derived cells (hUTC) treatment of stroke in rat.

    PubMed

    Jiang, Quan; Thiffault, Christine; Kramer, Brian C; Ding, Guang Liang; Zhang, Li; Nejad-Davarani, Siamak P; Li, Lian; Arbab, Ali S; Lu, Mei; Navia, Brad; Victor, Stephen J; Hong, Klaudyne; Li, Qing Jiang; Wang, Shi Yang; Li, Yi; Chopp, Michael

    2012-01-01

    Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential technology for neurorestoration and improvement of functional outcomes following stroke. Male Wistar rats were subjected to a transient middle cerebral artery occlusion (tMCAo) and were intravenously administered hUTC (N = 11) or vehicle (N = 10) 48 hrs after stroke. White matter and vascular reorganization was monitored over a 12-week period using MRI and histopathology. MRI results were correlated with neurological functional and histology outcomes to demonstrate that MRI can be a useful tool to measure structural recovery after stroke. MRI revealed a significant reduction in the ventricular volume expansion and improvement in cerebral blood flow (CBF) in the hUTC treated group compared to vehicle treated group. Treatment with hUTC resulted in histological and functional improvements as evidenced by enhanced expression of vWF and synaptophysin, and improved outcomes on behavioral tests. Significant correlations were detected between MRI ventricular volumes and histological lesion volume as well as number of apoptotic cells. A positive correlation was also observed between MRI CBF or cerebral blood volume (CBV) and histological synaptic density. Neurological functional tests were also significantly correlated with MRI ventricular volume and CBV. Our data demonstrated that MRI measurements can detect the effect of hUTC therapy on the brain reorganization and exhibited positive correlation with histological measurements of brain structural changes and functional behavioral tests after stroke. MRI ventricular volumes provided the most sensitive index in monitoring brain remodeling and treatment effects and highly correlated with histological and functional measurements. PMID:22900057

  15. Penumbra detection using PWI/DWI mismatch MRI in a rat stroke model with and without comorbidity: comparison of methods

    PubMed Central

    Reid, Emma; Graham, Delyth; Lopez-Gonzalez, M Rosario; Holmes, William M; Macrae, I Mhairi; McCabe, Christopher

    2012-01-01

    Perfusion-diffusion (perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI)) mismatch is used to identify penumbra in acute stroke. However, limitations in penumbra detection with mismatch are recognized, with a lack of consensus on thresholds, quantification and validation of mismatch. We determined perfusion and diffusion thresholds from final infarct in the clinically relevant spontaneously hypertensive stroke-prone (SHRSP) rat and its normotensive control strain, Wistar-Kyoto (WKY) and compared three methods for penumbra calculation. After permanent middle cerebral artery occlusion (MCAO) (WKY n=12, SHRSP n=15), diffusion-weighted (DWI) and perfusion-weighted (PWI) images were obtained for 4 hours post stroke and final infarct determined at 24 hours on T2 scans. The PWI/DWI mismatch was calculated from volumetric assessment (perfusion deficit volume minus apparent diffusion coefficient (ADC)-defined lesion volume) or spatial assessment of mismatch area on each coronal slice. The ADC-derived lesion growth provided the third, retrospective measure of penumbra. At 1 hour after MCAO, volumetric mismatch detected smaller volumes of penumbra in both strains (SHRSP: 31±50 mm3, WKY: 22±59 mm3, mean±s.d.) compared with spatial assessment (SHRSP: 36±15 mm3, WKY: 43±43 mm3) and ADC lesion expansion (SHRSP: 41±45 mm3, WKY: 65±41 mm3), although these differences were not statistically significant. Spatial assessment appears most informative, using both diffusion and perfusion data, eliminating the influence of negative mismatch and allowing the anatomical location of penumbra to be assessed at given time points after stroke. PMID:22669479

  16. MRI Detects Brain Reorganization after Human Umbilical Tissue-Derived Cells (hUTC) Treatment of Stroke in Rat

    PubMed Central

    Jiang, Quan; Thiffault, Christine; Kramer, Brian C.; Ding, Guang Liang; Zhang, Li; Nejad-Davarani, Siamak P.; Li, Lian; Arbab, Ali S.; Lu, Mei; Navia, Brad; Victor, Stephen J.; Hong, Klaudyne; Li, Qing Jiang; Wang, Shi Yang; Li, Yi; Chopp, Michael

    2012-01-01

    Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential technology for neurorestoration and improvement of functional outcomes following stroke. Male Wistar rats were subjected to a transient middle cerebral artery occlusion (tMCAo) and were intravenously administered hUTC (N = 11) or vehicle (N = 10) 48 hrs after stroke. White matter and vascular reorganization was monitored over a 12-week period using MRI and histopathology. MRI results were correlated with neurological functional and histology outcomes to demonstrate that MRI can be a useful tool to measure structural recovery after stroke. MRI revealed a significant reduction in the ventricular volume expansion and improvement in cerebral blood flow (CBF) in the hUTC treated group compared to vehicle treated group. Treatment with hUTC resulted in histological and functional improvements as evidenced by enhanced expression of vWF and synaptophysin, and improved outcomes on behavioral tests. Significant correlations were detected between MRI ventricular volumes and histological lesion volume as well as number of apoptotic cells. A positive correlation was also observed between MRI CBF or cerebral blood volume (CBV) and histological synaptic density. Neurological functional tests were also significantly correlated with MRI ventricular volume and CBV. Our data demonstrated that MRI measurements can detect the effect of hUTC therapy on the brain reorganization and exhibited positive correlation with histological measurements of brain structural changes and functional behavioral tests after stroke. MRI ventricular volumes provided the most sensitive index in monitoring brain remodeling and treatment effects and highly correlated with histological and functional measurements. PMID:22900057

  17. Guidelines for the Use of Echocardiography in the Evaluation of a Cardiac Source of Embolism.

    PubMed

    Saric, Muhamed; Armour, Alicia C; Arnaout, M Samir; Chaudhry, Farooq A; Grimm, Richard A; Kronzon, Itzhak; Landeck, Bruce F; Maganti, Kameswari; Michelena, Hector I; Tolstrup, Kirsten

    2016-01-01

    Embolism from the heart or the thoracic aorta often leads to clinically significant morbidity and mortality due to transient ischemic attack, stroke or occlusion of peripheral arteries. Transthoracic and transesophageal echocardiography are the key diagnostic modalities for evaluation, diagnosis, and management of stroke, systemic and pulmonary embolism. This document provides comprehensive American Society of Echocardiography guidelines on the use of echocardiography for evaluation of cardiac sources of embolism. It describes general mechanisms of stroke and systemic embolism; the specific role of cardiac and aortic sources in stroke, and systemic and pulmonary embolism; the role of echocardiography in evaluation, diagnosis, and management of cardiac and aortic sources of emboli including the incremental value of contrast and 3D echocardiography; and a brief description of alternative imaging techniques and their role in the evaluation of cardiac sources of emboli. Specific guidelines are provided for each category of embolic sources including the left atrium and left atrial appendage, left ventricle, heart valves, cardiac tumors, and thoracic aorta. In addition, there are recommendation regarding pulmonary embolism, and embolism related to cardiovascular surgery and percutaneous procedures. The guidelines also include a dedicated section on cardiac sources of embolism in pediatric populations. PMID:26765302

  18. Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments.

    PubMed

    Zhou, Feng; Chen, Liming; An, Qingzhu; Chen, Liang; Wen, Ying; Fang, Fang; Zhu, Wei; Yi, Tao

    2016-01-01

    We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X-ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice. PMID:27561915

  19. Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments

    PubMed Central

    Zhou, Feng; Chen, Liming; An, Qingzhu; Chen, Liang; Wen, Ying; Fang, Fang; Zhu, Wei; Yi, Tao

    2016-01-01

    We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X-ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice. PMID:27561915

  20. Computational identification of conserved transcription factor binding sites upstream of genes induced in rat brain by transient focal ischemic stroke.

    PubMed

    Pulliam, John V K; Xu, Zhenfeng; Ford, Gregory D; Liu, Cuimei; Li, Yonggang; Stovall, Kyndra C; Cannon, Virginetta S; Tewolde, Teclemichael; Moreno, Carlos S; Ford, Byron D

    2013-02-01

    Microarray analysis has been used to understand how gene regulation plays a critical role in neuronal injury, survival and repair following ischemic stroke. To identify the transcriptional regulatory elements responsible for ischemia-induced gene expression, we examined gene expression profiles of rat brains following focal ischemia and performed computational analysis of consensus transcription factor binding sites (TFBS) in the genes of the dataset. In this study, rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO) stroke and gene transcription in brain tissues following ischemia/reperfusion was examined using Affymetrix GeneChip technology. The CONserved transcription FACtor binding site (CONFAC) software package was used to identify over-represented TFBS in the upstream promoter regions of ischemia-induced genes compared to control datasets. CONFAC identified 12 TFBS that were statistically over-represented from our dataset of ischemia-induced genes, including three members of the Ets-1 family of transcription factors (TFs). Microarray results showed that mRNA for Ets-1 was increased following tMCAO but not pMCAO. Immunohistochemical analysis of Ets-1 protein in rat brains following MCAO showed that Ets-1 was highly expressed in neurons in the brain of sham control animals. Ets-1 protein expression was virtually abolished in injured neurons of the ischemic brain but was unchanged in peri-infarct brain areas. These data indicate that TFs, including Ets-1, may influence neuronal injury following ischemia. These findings could provide important insights into the mechanisms that lead to brain injury and could provide avenues for the development of novel therapies. PMID:23246490

  1. Pulmonary embolism

    PubMed Central

    Tarbox, Abigail K.; Swaroop, Mamta

    2013-01-01

    Pulmonary embolism (PE) is responsible for approximately 100,000 to 200,000 deaths in the United States each year. With a diverse range of clinical presentations from asymptomatic to death, diagnosing PE can be challenging. Various resources are available, such as clinical scoring systems, laboratory data, and imaging studies which help guide clinicians in their work-up of PE. Prompt recognition and treatment are essential for minimizing the mortality and morbidity associated with PE. Advances in recognition and treatment have also enabled treatment of some patients in the home setting and limited the amount of time spent in the hospital. This article will review the risk factors, pathophysiology, clinical presentation, evaluation, and treatment of PE. PMID:23724389

  2. Amniotic fluid embolism: review.

    PubMed

    Pantaleo, Greco; Luigi, Nappi; Federica, Trezza; Paola, Storelli; Margherita, Neri; Tahir, Mahmood

    2014-01-01

    Amniotic fluid embolism is a rare but dreadful syndrome in Obstetrics, which happens, in most of the cases, in the peripartum period. The actual "embolisation" of the pulmonary vessels does not explain the whole picture of the syndrome. An immune mechanism, similar to an anaphylactic reaction, is more convincingly the background of the event, but the pathogenesis is still ill-defined. Similarly the initial symptoms are difficult to interpret and distinguish from other acute and life-threatening emergencies (i.e. pulmonary embolism, placental abruption, septic shock, stroke, myocardial ischemia, etc.), therefore the diagnosis is one of exclusion, very often on postmortem report. Thus the prevalence of the disease is difficult to establish, most of the reports being postmortem cases or National Registries data. These data, based either on autopsy series or on registries, are non representative of the true prevalence of the event and obviously confusing for the correct understanding of the disease process. Risk factors are all those conditions or manouvres, which contemplate a breech in the maternal-fetal barrier. Again, given the rarity of the syndrome, no single event is clearly identifiable as a case-effect risk factor. Prognosis, which is obviously biased by the reporting system, is particularly grim both in terms of survival and morbidity. The symptoms being often elusive at the beginning, but rapidly and progressively catastrophic, a multidisciplinary team approach is warranted in order to provide the best chance of survival both for mother and baby. Immediate and aggressive resuscitation is, therefore, advised whenever a mother in labour or in the early postpartum period experiences a sudden collapse. PMID:24804726

  3. Mortality and Embolic Potential of Cardiac Tumors

    PubMed Central

    Dias, Ricardo Ribeiro; Fernandes, Fábio; Ramires, Félix José Alvarez; Mady, Charles; Albuquerque, Cícero Piva; Jatene, Fábio Biscegli

    2014-01-01

    Background Cardiac tumors are rare, mostly benign with high embolic potential. Objectives To correlate the histological type of cardiac masses with their embolic potential, implantation site and long term follow up in patients undergoing surgery. Methods Between January 1986 and December 2011, we retrospectively analyzed 185 consecutive patients who underwent excision of intracardiac mass (119 females, mean age 48±20 years). In 145 patients, the left atrium was the origin site. 72% were asymptomatic and prior embolization was often observed (19.8%). The diagnosis was established by echocardiography, magnetic resonance and histological examination. Results Most tumors were located in the left side of the heart. Myxoma was the most common (72.6%), followed by fibromas (6.9%), thrombi (6.4%) and sarcomas (6.4%). Ranging from 0.6cm to 15cm (mean 4.6 ± 2.5cm) 37 (19.8%) patients had prior embolization, stroke 10.2%, coronary 4.8%, peripheral 4.3% 5.4% of hospital death, with a predominance of malignant tumors (40% p < 0.0001). The histological type was a predictor of mortality (rhabdomyomas and sarcomas p = 0.002) and embolic event (sarcoma, lipoma and fibroelastoma p = 0.006), but not recurrence. Tumor size, atrial fibrillation, cavity and valve impairment were not associated with the embolic event. During follow-up (mean 80±63 months), there were 2 deaths (1.1%) and two recurrences 1 and 11 years after the operation, to the same cavity. Conclusion Most tumors were located in the left side of the heart. The histological type was predictor of death and preoperative embolic event, while the implantation site carries no relation with mortality or to embolic event. PMID:25029470

  4. Fat embolism syndrome

    PubMed Central

    George, Jacob; George, Reeba; Dixit, R.; Gupta, R. C.; Gupta, N.

    2013-01-01

    Fat embolism syndrome is an often overlooked cause of breathlessness in trauma wards. Presenting in a wide range of clinical signs of varying severity, fat embolism is usually diagnosed by a physician who keeps a high degree of suspicion. The clinical background, chronology of symptoms and corroborative laboratory findings are instrumental in a diagnosis of fat embolism syndrome. There are a few diagnostic criteria which are helpful in making a diagnosis of fat embolism syndrome. Management is mainly prevention of fat embolism syndrome, and organ supportive care. Except in fulminant fat embolism syndrome, the prognosis is usually good. PMID:23661916

  5. Cerebral air embolism caused by a bronchogenic cyst.

    PubMed

    Jung, Simon; Wiest, Roland; Frigerio, Susanna; Mattle, Heinrich P; Hess, Christian W

    2010-06-01

    An unusual case is presented of a tourist who developed fatal cerebral air embolism, pneumomediastinum and pneumopericardium while ascending from low altitude to Europe's highest railway station. Presumably the air embolism originated from rupture of the unsuspected bronchogenic cyst as a result of pressure changes during the ascent. Cerebral air embolism has been observed during surgery, in scuba diving accidents, submarine escapes and less frequently during exposure to very high altitude. People with known bronchogenic cysts should be informed about the risk of cerebral air embolism and surgical removal should be considered. Cerebral air embolism is a rare cause of coma and stroke in all activities with rapid air pressure changes, including alpine tourism, as our unfortunate tourist illustrates. PMID:20498190

  6. Cerebral infarction following thrombolysis for massive pulmonary embolism.

    PubMed

    Bracey, Tim S; Langrish, Chris; Darby, Mike; Soar, Jasmeet

    2006-01-01

    A 29-year-old male developed a fatal stroke 6 h after successful thrombolysis for massive pulmonary embolism. Autopsy showed thrombus protruding through a patent foramen ovale (PFO). A strand of thrombus extended from the aortic arch into the left common carotid artery. The brain showed extensive infarction of the left fronto-parietal area. Thrombolysis caused initial disintegration of the embolism. It is likely that thrombolysis caused fragments of clot to later break lose and embolise into the cerebral circulation. We discuss the need for risk stratification in patients who present with massive pulmonary embolism and PFO. PMID:16219407

  7. Changes in the cerebral blood flow in newborn rats assessed by LSCI and DOCT before and after the hemorrhagic stroke

    NASA Astrophysics Data System (ADS)

    Semyachkina-Glushkovskaya, O. V.; Lychagov, V. V.; Abdurashitov, A. S.; Sindeeva, O. V.; Sindeev, S. S.; Zinchenko, E. M.; Kajbeleva, E. I.; Pavlov, A. N.; Kassim, M.; Tuchin, V. V.

    2015-03-01

    The incidence of perinatal hemorrhagic stroke (HS) is very similar to that in the elderly and produces a significant morbidity and long-term neurologic and cognitive deficits. There is strong evidence that cerebral blood flow (CBF) abnormalities make considerable contribution to HS development. However, the mechanisms responsible for pathological changes in CBF in infants with HS are not established. Therefore, quantitative assessment of CBF may significantly advance the understanding of the nature of neonatal stroke. The aim of this investigation was to determine the particularities of alterations in macro- microcirculation in the brain of newborn rats in the different stages of stress-related development of HS using three-dimensional Doppler optical coherence tomography (DOCT) and laser speckle contrast imaging (LSCI).Our results show that cerebral veins are more sensitive to harmful effect of stress compared with microcirculatory vessels. Stress-induced progressive dilation of cerebral veins with the fall of blood flow velocity precedes HS while pathological changes in microcirculatory vessels are accompanied by development of HS. The further detailed study of cerebral venous and microcirculatory circulation would be a significant advance in development of prognostic criteria for a HS risk during the first days after birthday.

  8. Exercise pre‑conditioning alleviates brain damage via excitatory amino acid transporter 2 and extracellular signal‑regulated kinase 1/2 following ischemic stroke in rats.

    PubMed

    Wang, Xiao; Zhang, Min; Feng, Rui; Li, Wen-Bin; Ren, Shi-Qing; Zhang, Feng

    2015-02-01

    Previous studies have reported that physical exercise may exert a neuroprotective effect in humans as well as animals. However, the detailed mechanisms underlying the neuroprotective effect of exercise has remained to be elucidated. The aim of the present study was to explore the possible signaling pathways involved in the protective effect of pre‑ischemic treadmill training for ischemic stroke in rats. A total of 36 male Sprague‑Dawley rats were divided at random into three groups as follows (n=12 for each): Sham surgery group; middle cerebral artery occlusion (MCAO) group; and exercise with MCAO group. Following treadmill training for three weeks, the middle cerebral artery was occluded for 90 min in order to induce ischemic stroke, followed by reperfusion. Following 24 h post‑reperfusion, six rats from each group were assessed for neurological deficits and then sacrificed to calculate the infarct volume. The remaining rats (n=6 for each group) were sacrificed and the expression levels of excitatory amino acid transporter 2 (EAAT‑2) and extracellular signal‑regulated kinase 1/2 (ERK1/2) were detected using western blot analysis. The results of the present study demonstrated that rats that underwent pre‑ischemic exercise intervention had a significantly decreased brain infarct volume and neurological deficits; in addition, the pre‑ischemic exercise group showed decreased overexpression of phosphorylated ERK1/2 and increased expression of EAAT‑2 following ischemic stroke. In conclusion, treadmill training exercise prior to ischemic stroke alleviated brain damage in rats via regulation of EAAT‑2 and ERK1/2. PMID:25370789

  9. [Features of memantine action profile in cholinergic deficit and intracerebral posttraumatic hematoma (hemorrhagic stroke) models in rats].

    PubMed

    Garibova, T L; Voronina, T A; Litvinova, S A; Kuznetsova, A L; Kul'chikov, A E; Alesenko, A V

    2008-01-01

    Memantine, a low-affinity non-competitive antagonist of glutamatergic NMDA-subtype receptors, was used at a daily dose of 1 mg/kg over 10 days for the treatment of rats with cholinergic deficit induced by the chronic administration of scopolamine (1 mg/kg, 20 days). The drug prevented violation of the learning of conditioned active and passive avoidance reflexes and produced no significant effect on the emotional state of animals in elevated plus maze (EPM) test. In animals with intracerebral posttraumatic hematoma (hemorrhagic stroke), memantine (2 mg/kg, for 3 days after operation) completely prevented the loss of animals, reduced the neurological deficit, improved conditioned passive avoidance reflex performance, and decreased emotional stress in the EPM test. PMID:18488899

  10. Comparisons between Garcia, Modo, and Longa rodent stroke scales: Optimizing resource allocation in rat models of focal middle cerebral artery occlusion.

    PubMed

    Bachour, Salam P; Hevesi, Mario; Bachour, Ornina; Sweis, Brian M; Mahmoudi, Javad; Brekke, Julia A; Divani, Afshin A

    2016-05-15

    The use of rodent stroke models allow for the understanding of stroke pathophysiology. There is currently no gold standard neurological assessment to measure deficits and recovery from stroke in rodent models. Agreement on a universal preclinical stroke scale allows for comparison of the outcomes among conducted studies. The present study aimed to compare three routinely used neurological assessments in rodent studies (i.e., Garcia, Modo, and Longa) to determine which is most effective for accurately and consistently quantifying neurological deficits in the context of focal middle cerebral artery occlusion (MCAo) in rats. Focal MCAo was induced in 22 male Wistar rats using a novel transfemoral approach. Rodents were assessed for neurological deficit pre-injury as well as 3 and 24h post-injury. Data was analyzed to determine Pearson correlation coefficients in addition to McNemar's χ(2) values between each pair of neurological assessments. All three stroke scales, Garcia, Modo, and Longa, showed statistically significant changes between the baseline and the 3-hour neurological assessments. A trend towards neurological recovery was observed in all three stroke scales between the 3 and 24-hour endpoints. The three scales were highly correlated with each other, with Garcia and Modo having the strongest correlation. Of the three pairwise analyses, the comparison between the Garcia and Longa tests demonstrated the highest McNemar's χ(2) value, indicating least marginal homogeneity between these two tests. The combination of high correlation between Garcia and Modo tests along with greatest marginal heterogeneity observed between the Garcia and Longa test lead us to recommend the use of Garcia and Longa neurological scales when researchers are hoping to capture the broadest range of neurological factors using only two stroke scales. PMID:27084232

  11. Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery

    PubMed Central

    Weston, Robert M.; Lin, Bin; Dusting, Gregory J.; Roulston, Carli L.

    2013-01-01

    NADPH oxidase is a major source of superoxide anion following stroke and reperfusion. This study evaluated the effects of apocynin, a known antioxidant and inhibitor of Nox2 NADPH, on neuronal injury and cell-specific responses to stroke induced in the conscious rat. Apocynin treatment (50 mg/kg i.p.) commencing 1 hour prior to stroke and 24 and 48 hours after stroke significantly reduced infarct volume in the cortex by ~ 60%, but had no effect on striatal damage or neurological deficits. In situ detection of reactive oxygen species (ROS) using dihydroethidium fluorescence revealed that increased ROS detected in OX-42 positive cells following ischemia was reduced in apocynin-treated rats by ~ 51%, but surprisingly increased in surrounding NeuN positive cells of the same rats by ~ 27%, in comparison to the contralateral hemisphere. Reduced ROS from activated microglia/macrophages treated with apocynin was associated with reduced Nox2 immunoreactivity without change to the number of cells. These findings confirm the protective effects of apocynin and indicate a novel mechanism via reduced Nox2 expression. We also reveal compensatory changes in neuronal ROS generation as a result of Nox2 inhibition and highlight the need to assess long term individual cell responses to inhibitors of oxidative stress. PMID:23401848

  12. Quantitative Susceptibility Mapping-Based Microscopy of Magnetic Resonance Venography (QSM-mMRV) for In Vivo Morphologically and Functionally Assessing Cerebromicrovasculature in Rat Stroke Model

    PubMed Central

    Hsieh, Meng-Chi; Tsai, Ching-Yi; Liao, Min-Chiao; Yang, Jenq-Lin; Su, Chia-Hao; Chen, Jyh-Horng

    2016-01-01

    Abnormal cerebral oxygenation and vessel structure is a crucial feature of stroke. An imaging method with structural and functional information is necessary for diagnosis of stroke. This study applies QSM-mMRV (quantitative susceptibility mapping-based microscopic magnetic resonance venography) for noninvasively detecting small cerebral venous vessels in rat stroke model. First, susceptibility mapping is optimized and calculated from magnetic resonance (MR) phase images of a rat brain. Subsequently, QSM-mMRV is used to simultaneously provide information on microvascular architecture and venous oxygen saturation (SvO2), both of which can be used to evaluate the physiological and functional characteristics of microvascular changes for longitudinally monitoring and therapeutically evaluating a disease model. Morphologically, the quantification of vessel sizes using QSM-mMRV was 30% smaller than that of susceptibility-weighted imaging (SWI), which eliminated the overestimation of conventional SWI. Functionally, QSM-mMRV estimated an average SvO2 ranging from 73% to 85% for healthy rats. Finally, we also applied QSM to monitor the revascularization of post-stroke vessels from 3 to 10 days after reperfusion. QSM estimations of SvO2 were comparable to those calculated using the pulse oximeter standard metric. We conclude that QSM-mMRV is useful for longitudinally monitoring blood oxygen and might become clinically useful for assessing cerebrovascular diseases. PMID:26974842

  13. Cerebral Air Embolism from Angioinvasive Cavitary Aspergillosis

    PubMed Central

    Lin, Chen; Barrio, George A.; Hurwitz, Lynne M.; Kranz, Peter G.

    2014-01-01

    Background. Nontraumatic cerebral air embolism cases are rare. We report a case of an air embolism resulting in cerebral infarction related to angioinvasive cavitary aspergillosis. To our knowledge, there have been no previous reports associating these two conditions together. Case Presentation. A 32-year-old female was admitted for treatment of acute lymphoblastic leukemia (ALL). Her hospital course was complicated by pulmonary aspergillosis. On hospital day 55, she acutely developed severe global aphasia with right hemiplegia. A CT and CT-angiogram of her head and neck were obtained demonstrating intravascular air emboli within the left middle cerebral artery (MCA) branches. She was emergently taken for hyperbaric oxygen therapy (HBOT). Evaluation for origin of the air embolus revealed an air focus along the left lower pulmonary vein. Over the course of 48 hours, her symptoms significantly improved. Conclusion. This unique case details an immunocompromised patient with pulmonary aspergillosis cavitary lesions that invaded into a pulmonary vein and caused a cerebral air embolism. With cerebral air embolisms, the acute treatment option differs from the typical ischemic stroke pathway and the provider should consider emergent HBOT. This case highlights the importance of considering atypical causes of acute ischemic stroke. PMID:25197589

  14. Intravenous administration of adipose tissue-derived stem cells enhances nerve healing and promotes BDNF expression via the TrkB signaling in a rat stroke model

    PubMed Central

    Li, Xin; Zheng, Wei; Bai, Hongying; Wang, Jin; Wei, Ruili; Wen, Hongtao; Ning, Hanbing

    2016-01-01

    Previous studies have shown the beneficial effects of adipose-derived stem cells (ADSCs) transplantation in stroke. However, the molecular mechanism by which transplanted ADSCs promote nerve healing is not yet elucidated. In order to make clear the molecular mechanism for the neuroprotective effects of ADSCs and investigate roles of the BDNF–TrkB signaling in neuroprotection of ADSCs, we, therefore, examined the neurological function, brain water content, and the protein expression in middle cerebral artery occlusion (MCAO) rats with or without ADSCs transplantation. ADSCs were transplanted intravenously into rats at 30 minutes after MCAO. K252a, an inhibitor of TrkB, was administered into rats by intraventricular and brain stereotaxic injection. Modified neurological severity score tests were performed to measure behavioral outcomes. The results showed that ADSCs significantly alleviated neurological deficits and reduced brain water content in MCAO rats. The protein expression levels of BDNF and TrkB significantly increased in the cortex of MCAO rats with ADSCs treatment. However, K252a administration reversed the ADSCs-induced elevation of BDNF, TrkB, and Bcl-2 and reduction of Bax protein in MCAO rats. ADSCs promote BDNF expression via the TrkB signaling and improve functional neurological recovery in stroke rats. PMID:27330296

  15. Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke

    PubMed Central

    Ishida, Akimasa; Isa, Kaoru; Umeda, Tatsuya; Kobayashi, Kazuto; Kobayashi, Kenta; Hida, Hideki

    2016-01-01

    Intensive rehabilitation is believed to induce use-dependent plasticity in the injured nervous system; however, its causal relationship to functional recovery is unclear. Here, we performed systematic analysis of the effects of forced use of an impaired forelimb on the recovery of rats after lesioning the internal capsule with intracerebral hemorrhage (ICH). Forced limb use (FLU) group rats exhibited better recovery of skilled forelimb functions and their cortical motor area with forelimb representation was restored and enlarged on the ipsilesional side. In addition, abundant axonal sprouting from the reemerged forelimb area was found in the ipsilateral red nucleus after FLU. To test the causal relationship between the plasticity in the cortico-rubral pathway and recovery, loss-of-function experiments were conducted using a double-viral vector technique, which induces selective blockade of the target pathway. Blockade of the cortico-rubral tract resulted in deficits of the recovered forelimb function in FLU group rats. These findings suggest that the cortico-rubral pathway is a substrate for recovery induced by intensive rehabilitation after ICH. SIGNIFICANCE STATEMENT The research aimed at determining the causal linkage between reorganization of the motor pathway induced by intensive rehabilitative training and recovery after stroke. We clarified the expansion of the forelimb representation area of the ipsilesional motor cortex by forced impaired forelimb use (FLU) after lesioning the internal capsule with intracerebral hemorrhaging (ICH) in rats. Anterograde tracing showed robust axonal sprouting from the forelimb area to the red nucleus in response to FLU. Selective blockade of the cortico-rubral pathway by the novel double-viral vector technique clearly revealed that the increased cortico-rubral axonal projections had causal linkage to the recovery of reaching movements induced by FLU. Our data demonstrate that the cortico-rubral pathway is responsible for the

  16. Sardine peptide with angiotensin I-converting enzyme inhibitory activity improves glucose tolerance in stroke-prone spontaneously hypertensive rats.

    PubMed

    Otani, Lila; Ninomiya, Toshio; Murakami, Megumi; Osajima, Katsuhiro; Kato, Hisanori; Murakami, Tetsuo

    2009-10-01

    An enzymatic hydrolysate of sardine protein (sardine peptide, SP) derived from sardine muscle possesses angiotensin I-converting enzyme (ACE) inhibitory activity. In the present study, we investigated the effect of SP on the blood glucose levels in stroke-prone spontaneously hypertensive rats (SHRSPs). Ten-week-old SHRSPs were assigned to three groups. The control group was given tap water for 4 weeks, while the experimental groups were given water containing SP (1 g/kg/d) or an ACE inhibitor, captopril (8 mg/kg/d). Treatment with SP and captopril decreased ACE activity in the kidney, aorta, and mesentery. There were no differences in fasting blood glucose levels among the three groups, whereas SP and captopril administration significantly suppressed the increase in blood glucose after glucose loading in the control SHRSPs. No difference was observed in plasma insulin levels among the three groups. Thus treatment with captopril and ACE-inhibitory sardine peptides ameliorated the glucose tolerance of this rat strain. PMID:19809178

  17. Long-term survival in permanent middle cerebral artery occlusion: a model of malignant stroke in rats

    PubMed Central

    Shanbhag, Nagesh C.; Henning, Robert H.; Schilling, Lothar

    2016-01-01

    Occlusion of the middle cerebral artery (MCA) by an intraluminal filament is widely used to study focal brain ischemia in male Sprague-Dawley rats. However, permanent occlusion goes along with a high fatality. To overcome this drawback we designed a new filament carrying a bowling pin-shaped tip (BP-tip) and compared this with three conventionally tipped filaments. Follow-up periods were 24 h (all groups) and 72 and 120 h in BP-tip group. Ischemic damage and swelling were quantified using silver nitrate staining. Collateral flow via the posterior cerebral artery (PCA) was assessed using selective dye perfusion of the internal carotid artery. Despite a comparable decrease of brain perfusion in all groups, ischemic damage was significantly smaller in BP-tips (p < 0.05). Moreover, BP-tip significantly reduced mortality from 60% to 12.5% and widely spared the occipital region and hypothalamus from ischemic damage. Conventional but not BP-tip filaments induced vascular distortion, measured as gross displacement of the MCA origin, which correlated with occipital infarction size. Accordingly, BP-tip occluded rats showed a significantly better collateral filling of the PCA territory. Ischemic volume significantly increased in BP-tip occlusion at 72 h follow-up. BP-tip filaments offer superior survival in permanent MCA occlusion, while mimicking the course of a malignant stroke in patients. PMID:27329690

  18. High resolution 23Na-nuclear magnetic resonance study of stroke-prone spontaneously hypertensive rat erythrocytes.

    PubMed

    Kwan, C Y; Seo, Y; Ito, H; Murakami, M; Watari, H

    1987-06-01

    The intracellular Na+ content of washed erythrocytes from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY) was measured by a high resolution 23Na-nuclear magnetic resonance (NMR) technique using a non-permeant aqueous shift reagent, dysprosium triethylenetetramine hexaacetic acid, Dy(TTHA)3-. The initial intracellular Na+ of freshly isolated and washed erythrocytes was very low (approximately 5 mmol/l) and increased progressively with prolonged incubation in isotonic salt solution at 37 degrees C. There was no significant difference in the erythrocyte Na+ concentration between SHRSP and WKY over the entire period of measurement, nor was any difference detected in their osmotic fragility or total cellular volume, although the osmotic fragility decreased with incubation time. The high energy phosphate metabolites were also studied in the same erythrocytes by 31P-NMR. The level of intracellular ATP decreased with incubation at 37 degrees C but showed no difference between the SHRSP and WKY samples. Inclusion of 1 mmol/l ouabain in the incubation medium substantially retarded the breakdown of intracellular ATP and resulted in a concomitant increase in intracellular Na+. However, neither the ouabain-sensitive nor the ouabain-insensitive component of Na+ influx altered in SHRSP erythrocytes compared with WKY erythrocytes in paired experiments. Our results do not support the hypothesis that altered Na+ transport, resulting in an increase in erythrocyte Na+ concentration, is associated with spontaneous hypertension. PMID:3611783

  19. Spontaneous white matter lesion in brain of stroke-prone renovascular hypertensive rats: a study from MRI, pathology and behavior.

    PubMed

    Fan, Yuhua; Lan, Linfang; Zheng, Lu; Ji, Xiaotan; Lin, Jing; Zeng, Jinsheng; Huang, Ruxun; Sun, Jian

    2015-12-01

    Hypertension is considered one of the most important controllable risk factors for white matter lesion (WML). Our previous work found that stroke-prone renovascular hypertensive rats (RHRSP) displayed a high rate of WML. This study aimed to investigate the WML in RHRSP from MRI, pathology and behavior. RHRSP model was established by two-kidney, two-clipmethod and kept for 20 weeks. WML was decteted by magnetic resonance imaging (MRI) and loyez staining. Cognition was tested by morris water maze (MWM). Vascular changes were observed by HE staining on brain and carotid sections. Ultrastucture of blood brain barrier (BBB) were observed by transmission electron microscope. Immunofluorescence was used to detect albumin leakage and cell proliferation. T(2)-weighted MRI scans of RHRSP displayed diffuse, confluent white-matter hyperintensities. Pathological examination of the same rat showed marked vacuoles, disappearence of myelin and nerve fibers in white matter, supporting the neuroimaging findings. Spatial learning and memory impairment were observed in RHRSP. The small arteries in brain exhibited fibrinoid necrosis, hyalinosis and vascular remodeling. BBB disruption and plasma albumin leakage into vascular wall was observed in RHRSP. Increased cell proliferation in subventricular zone was seen in RHRSP. RHRSP demonstrated spontaneous WML and cognitive impairment. Hypertensive small vessel lesions and BBB disruption might paly causative factors for the onset and development of WML. The characteristic features of WML in RHRSP suggested it a valid animal model for WML. PMID:26387009

  20. Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke.

    PubMed

    Wu, Ming-Hsiu; Huang, Chao-Ching; Chio, Chung-Ching; Tsai, Kuen-Jer; Chang, Ching-Ping; Lin, Nan-Kai; Lin, Mao-Tsun

    2016-09-01

    Ischemic stroke, caused by obstruction of blood flow to the brain, would initiate microglia activation which contributes to neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation could be a therapeutic strategy for ischemic stroke. This study was aimed to elucidate the anti-inflammatory effects of alpha-lipoic acid and etanercept given either singly or in combination in rats subjected to middle cerebral artery occlusion. Both α-lipoic acid and etanercept markedly reduced cerebral infarct, blood-brain barrier disruption, and neurological motor deficits with the former drug being more effective with the dosage used. Furthermore, when used in combination, the reduction was more substantial. Remarkably, a greater diminution in the serum levels of tumor necrosis factor-alpha as well as the brain levels of microglial activation (e.g., microgliosis, amoeboid microglia, and microglial overexpression of tumor necrosis factor-α) was observed with the combined drug treatment as compared to the drugs given separately. We conclude that inhibition of peripheral tumor necrosis factor-alpha as well as downregulation of brain microglial activation by alpha-lipoic acid or etanercept protect rat brain against ischemic stroke. Moreover, when both drugs were used in combination, the stroke recovery was promoted more extensively. PMID:26374550

  1. Peri-infarct depolarizations during focal ischemia in the awake Spontaneously Hypertensive Rat. Minimizing anesthesia confounds in experimental stroke.

    PubMed

    Kudo, K; Zhao, L; Nowak, T S

    2016-06-14

    Anesthesia profoundly impacts peri-infarct depolarizations (PIDs), but only one prior report has described their monitoring during experimental stroke in awake animals. Since temporal patterns of PID occurrence are model specific, the current study examined PID incidence during focal ischemia in the awake Spontaneously Hypertensive Rat (SHR), and documented the impact of both prior and concurrent isoflurane anesthesia. For awake recordings, electrodes were implanted under isoflurane anesthesia 1day to 5weeks prior to occlusion surgery. Rats were then subjected to permanent or transient (2h) tandem occlusion of the middle cerebral and ipsilateral common carotid arteries, followed by PID monitoring for up to 3days. Comparison perfusion imaging studies evaluated PID-associated hyperemic transients during permanent ischemia under anesthesia at varied intervals following prior isoflurane exposure. Prior anesthesia attenuated PID number at intervals up to 1week, establishing 2weeks as a practical recovery duration following surgical preparation to avoid isoflurane preconditioning effects. PIDs in awake SHR were limited to the first 4h after permanent occlusions. Maintaining anesthesia during this interval reduced PID number, and prolonged their occurrence through several hours following anesthesia termination. Although PID number otherwise correlated with infarct size, PID suppression by anesthesia was not protective in the absence of reperfusion. PIDs persisted up to 36h after transient occlusions. These results differ markedly from the one previous report of such monitoring in awake Sprague-Dawley rats, which found an extended biphasic PID time course during 24h after both permanent and transient filament occlusions. PID occurrence closely reflects the time course of infarct progression in the respective models, and may be more useful than absolute PID number as an index of ongoing pathology. PMID:27026594

  2. Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers.

    PubMed

    Michihara, Akihiro; Ide, Norie; Mizutani, Yurika; Okamoto, Manami; Uchida, Maya; Matsuoka, Hiroshi; Akasaki, Kenji

    2015-01-01

    Hypocholesterolemia has been epidemiologically identified as one of the causes of stroke (cerebral hemorrhage). We previously reported that lower protein levels of mevalonate pyrophosphate decarboxylase (MPD), which is responsible for reducing serum cholesterol levels in stroke-prone spontaneously hypertensive rats (SHRSP), in the liver were caused by a reduction in mRNA levels. However, the mechanism responsible for reducing MPD expression levels in the SHRSP liver remains unclear. Thus, we compared microRNA (miR)-214 combined with the 3'-untranslated region of MPD mRNA and heterogeneous nuclear RNA (hnRNA) between SHRSP and normotensive Wistar Kyoto rats (WKY). miR-214 levels in the liver were markedly higher in SHRSP than in WKY, whereas hnRNA levels were significantly lower. These results indicate that the upregulation of miR-214 and downregulation of MPD transcription in the liver both play a role in the development of hypocholesterolemia in SHRSP. PMID:26158200

  3. Ischemic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  4. Pediatric Stroke

    MedlinePlus

    ... Trials News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis ... UT Southwestern Medical Center. Copyright © 1997-2016 - The Internet Stroke Center. All rights reserved. The information contained ...

  5. Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats

    PubMed Central

    Weise, Gesa; Lorenz, Marlene; Pösel, Claudia; Maria Riegelsberger, Ute; Störbeck, Veronika; Kamprad, Manja; Kranz, Alexander; Wagner, Daniel-Christoph; Boltze, Johannes

    2014-01-01

    Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing. PMID:24169850

  6. PSA-NCAM(+) neural precursor cells from human embryonic stem cells promote neural tissue integrity and behavioral performance in a rat stroke model.

    PubMed

    Kim, Han-Soo; Choi, Seong-Mi; Yang, Wonsuk; Kim, Dae-Sung; Lee, Dongjin R; Cho, Sung-Rae; Kim, Dong-Wook

    2014-12-01

    Recently, cell-based therapy has been highlighted as an alternative to treating ischemic brain damage in stroke patients. The present study addresses the therapeutic potential of polysialic acid-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (NPC(PSA-NCAM+)) derived from human embryonic stem cells (hESCs) in a rat stroke model with permanent middle cerebral artery occlusion. Data showed that rats transplanted with NPC(PSA-NCAM+) are superior to those treated with phosphate buffered saline (PBS) or mesenchymal stem cells (MSCs) in behavioral performance throughout time points. In order to investigate its underlying events, immunohistochemical analysis was performed on rat ischemic brains treated with PBS, MSCs, and NPC(PSA-NCAM+). Unlike MSCs, NPC(PSA-NCAM+) demonstrated a potent immunoreactivity against human specific nuclei, doublecortin, and Tuj1 at day 26 post-transplantation, implying their survival, differentiation, and integration in the host brain. Significantly, NPC(PSA-NCAM+) evidently lowered the positivity of microglial ED-1 and astrocytic GFAP, suggesting a suppression of adverse glial activation in the host brain. In addition, NPC(PSA-NCAM+) elevated α-SMA(+) immunoreactivity and the expression of angiopoietin-1 indicating angiogenic stimulation in the host brain. Taken together, the current data demonstrate that transplanted NPC(PSA-NCAM+) preserve brain tissue with reduced infarct size and improve behavioral performance through actions encompassing anti-reactive glial activation and pro-angiogenic activity in a rat stroke model. In conclusion, the present findings support the potentiality of NPC(PSA-NCAM+) as the promising source in the development of cell-based therapy for neurological diseases including ischemic stroke. PMID:24974101

  7. Physical exercise regulates neural stem cells proliferation and migration via SDF-1α/CXCR4 pathway in rats after ischemic stroke.

    PubMed

    Luo, Jing; Hu, Xiquan; Zhang, Liying; Li, Lili; Zheng, Haiqing; Li, Menglin; Zhang, Qingjie

    2014-08-22

    Physical exercise is beneficial to functional recovery after stroke. But its underling mechanism is still unknown. It is reported that neural stem cells (NSCs) proliferation, migration and differentiation play an important role in recovery following stroke, furthermore, stromal cell derived factor-1α (SDF-1α) and its chemokine receptor type 4 (CXCR4) regulate NSCs migration. This study is aimed to examine whether physical exercise improves functional recovery by enhancing NSCs proliferation, migration and differentiation through SDF-1α/CXCR4 axis in rats after ischemic stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with physical exercise after MCAO. AMD3100 (an antagonist of CXCR4) was used to confirm the effect of SDF-1α/CXCR4 axis on exercise-mediated NSCs mobilization. We found that physical exercise improved functional recovery and reduced infarct volume. Moreover, 5-bromo-2'-deoxyuridine (BrdU), doublecortin (Dcx)-positive cells in the ipsilateral SVZ and BrdU/neuron-specific nuclear protein (NeuN)-positive cells in the ipsilateral striatum were increased by physical exercise. Simultaneously, SDF-1α-positive cells were significantly higher in physical exercise group than those in control group. Our results indicate that physical exercise improves functional recovery in ischemic rats possibly by enhancement of NSCs proliferation, migration in the SVZ and differentiation in the damaged striatum. Moreover, SDF-1α/CXCR4 pathway involves in exercise-mediated NSCs proliferation and migration but not differentiation. PMID:25010020

  8. Simultaneous MR imaging for tissue engineering in a rat model of stroke

    PubMed Central

    Nicholls, Francesca J.; Ling, Wen; Ferrauto, Giuseppe; Aime, Silvio; Modo, Michel

    2015-01-01

    In situ tissue engineering within a stroke cavity is gradually emerging as a novel therapeutic paradigm. Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging. The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment. The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents. The development of sophisticated imaging methods is essential to guide delivery of the building blocks for in situ tissue engineering, but will also be essential to understand the dynamics of cellular interactions leading to the formation of de novo tissue. PMID:26419200

  9. Embolic Protection Devices in Transcatheter Aortic Valve Replacement.

    PubMed

    Steinvil, Arie; Benson, Richard T; Waksman, Ron

    2016-03-01

    The initially reported periprocedural neurological events rates associated with transcatheter aortic valve replacement raised concerns that ultimately led to the development and to the clinical research of novel embolic protection devices. Although the reduction of clinical stroke is a desired goal, the current research design of embolic protection devices focuses on surrogate markers of the clinical disease, primarily on silent central nervous system lesions observed in postprocedural diffuse-weighted magnetic resonance imaging and cognitive function testing. As the mere presence of particulate debris in brain matter may not correlate with the extent of brain injury, cognitive function, or quality of life, the clinical significance of embolic protection devices has yet to be determined, and interpretation of study results with regard to real-life clinical use should be viewed accordingly. The purpose of this article is to provide an overview of the updated ongoing clinical research on embolic protection devices and present its major caveats. PMID:26951618

  10. PcTx1 affords neuroprotection in a conscious model of stroke in hypertensive rats via selective inhibition of ASIC1a.

    PubMed

    McCarthy, Claudia A; Rash, Lachlan D; Chassagnon, Irène R; King, Glenn F; Widdop, Robert E

    2015-12-01

    Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and plays a major role in neuronal injury following cerebral ischemia. Evidence that inhibition of ASIC1a might be neuroprotective following stroke was previously obtained using "PcTx1 venom" from the tarantula Psalmopeous cambridgei. We show here that the ASIC1a-selective blocker PcTx1 is present at only 0.4% abundance in this venom, leading to uncertainty as to whether the observed neuroprotective effects were due to PcTx1 blockade of ASIC1a or inhibition of other ion channels and receptors by the hundreds of peptides and small molecules present in the venom. We therefore examined whether pure PcTx1 is neuroprotective in a conscious model of stroke via direct inhibition of ASIC1a. A focal reperfusion model of stroke was induced in conscious spontaneously hypertensive rats (SHR) by administering endothelin-1 to the middle cerebral artery via a surgically implanted cannula. Two hours later, SHR were treated with a single intracerebroventricular (i.c.v.) dose of PcTx1 (1 ng/kg), an ASIC1a-inactive mutant of PcTx1 (1 ng/kg), or saline, and ledged beam and neurological tests were used to assess the severity of symptomatic changes. PcTx1 markedly reduced cortical and striatal infarct volumes measured 72 h post-stroke, which correlated with improvements in neurological score, motor function and preservation of neuronal architecture. In contrast, the inactive PcTx1 analogue had no effect on stroke outcome. This is the first demonstration that selective pharmacological inhibition of ASIC1a is neuroprotective in conscious SHRs, thus validating inhibition of ASIC1a as a potential treatment for stroke. PMID:26320544

  11. Acute Blockage of Notch Signaling by DAPT Induces Neuroprotection and Neurogenesis in the Neonatal Rat Brain After Stroke.

    PubMed

    Li, Zhongxia; Wang, Jiangping; Zhao, Congying; Ren, Keming; Xia, Zhezhi; Yu, Huimin; Jiang, Kewen

    2016-04-01

    Notch signaling is critically involved in various biological events. Notch undergoes cleavage by the γ-secretase enzyme to release Notch intracellular domain that will translocate into nucleus to result in expression of target gene. γ-Secretase inhibitors have been developed as potential treatments for neurological degenerative diseases, but its effects against ischemic injury remain relatively uncertain. In the present study, we demonstrated that N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor not only rescued the cerebral hypoperfusion or ischemia neonatal rats from death, reduced apoptosis in penumbra, but also reduced brain infarct size. Furthermore, DAPT elicited some morphologic hallmarks such as neurogenesis and angiogenesis that related to the brain repair and functional recovery after stroke: increased accumulations of newborn cells in the peri-infarct region with a higher fraction of them adopting immature neuronal and glial markers instead of microglial markers on 5 days, enhanced vascular densities in penumbra at 14 days, and evident regulations of the gene profiles associated with neurogenesis in penumbral tissues. The current results suggest that DAPT is a potential neuroprotectants against ischemic injury in immature brain, and future treatment strategies such as clinical trials using γ-secretase inhibitors would be an attractive therapy for perinatal ischemia. PMID:26691164

  12. Crocetin, a carotenoid from Gardenia jasminoides Ellis, protects against hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats.

    PubMed

    Higashino, Saori; Sasaki, Yasuto; Giddings, John C; Hyodo, Kanae; Sakata, Shigeko Fujimoto; Matsuda, Koichi; Horikawa, Yoko; Yamamoto, Junichiro

    2014-09-01

    Crocetin is a natural carotenoid dicarboxylic acid that is found in the fruit of Gardenia jasminoides Ellis (Cape Jasmine) and in the stamen and pistil of Crocus sativus L. (saffron). It is used worldwide as an important spice, food colorant, and herbal medicine. In the current investigation, we have examined the cardiovascular effects of crocetin using stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs (6 weeks old) were classified into three groups: a control group and two crocetin groups (25 and 50 mg/kg/day). The animals were given crocetin for 3 weeks. Body weights in each group were not significantly different during the treatment period, but the increase in systolic blood pressures observed with age was significantly moderated by crocetin. Thrombogenesis, assessed using a He-Ne laser technique in pial vessels, was significantly decreased. Antioxidant activity, assessed by measuring urinary 8-hydroxy-2'-deoxyguanosine levels, together with urinary nitric oxide (NO) metabolite levels, was increased significantly after treatment. Acetylcholine-induced vasodilation was measured using the aorta and indicated that endothelial function was significantly improved by crocetin. These results strongly suggest that the antihypertensive and antithrombotic effects of crocetin were related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species. PMID:24550159

  13. Protective effects of allicin against ischemic stroke in a rat model of middle cerebral artery occlusion.

    PubMed

    Zhang, Benping; Li, Feng; Zhao, Weijiang; Li, Jiebing; Li, Qingsong; Wang, Weizhi

    2015-09-01

    Allicin, a molecule predominantly responsible for the pungent odor and the antibiotic function of garlic, exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of various disorders. The present study aimed to elucidate the effect of allicin in cerebral ischemia/reperfusion (I/R) injury in rats. Rats were subjected to 1.5 h of transient middle cerebral artery occlusion (MCAO), followed by 24 h of reperfusion. Rats were randomly assigned to the sham surgery group, the MCAO group and the MCAO + allicin group. Neurological score, cerebral infarct size, brain water content, neuronal apoptosis, serum tumor necrosis factor (TNF)‑α and myeloperoxidase (MPO) activity were measured. The results suggested that allicin reduced cerebral infarction area, brain water content, neuronal apoptosis, TNF‑α levels and MPO activity in the serum. The results of the present study indicated that allicin protects the brain from cerebral I/R injury, which may be ascribed to its anti‑apoptotic and anti‑inflammatory effects. PMID:26045182

  14. Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model

    PubMed Central

    Selvamani, Amutha; Williams, Madison H.; Miranda, Rajesh C.; Sohrabji, Farida

    2015-01-01

    Small non-coding RNA [miRNA (microRNA)] found in the circulation have been used successfully as biomarkers and mechanistic targets for chronic and acute disease. The present study investigated the impact of age and sex on miRNA expression following ischaemic stroke in an animal model. Adult (6 month) and middle-aged (11–12 months) female and male rats were subject to MCAo (middle cerebral artery occlusion) using ET-1 (endothelin-1). Circulating miRNAs were analysed in blood samples at 2 and 5 days post-stroke, and brain miRNAs were analysed at 5 days post-stroke. Although stroke-associated infarction was observed in all groups, infarct volume and sensory-motor deficits were significantly reduced in adult females compared with middle-aged females, adult males or middle-aged males. At 2 days post-stroke, 21 circulating miRNAs were differentially regulated and PCA (principal component analysis) confirmed that most of the variance was due to age. At 5 days post-stroke, 78 circulating miRNAs exhibited significantly different regulation, and most of the variance was associated with sex. A small cohort (five) of miRNAs, miR-15a, miR-19b, miR-32 miR-136 and miR-199a-3p, were found to be highly expressed exclusively in adult females compared with middle-aged females, adult males and middle-aged males. Predicted gene targets for these five miRNAs analysed for KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed that the top ten KEGG pathways were related to growth factor signalling, cell structure and PI3K (phosphoinositide 3-kinase)/Akt and mTOR (mammalian target of rapamycin) signalling. Overall, the pattern of circulating miRNA expression suggests an early influence of age in stroke pathology, with a later emergence of sex as a factor for stroke severity. PMID:24428837

  15. Increased Expression of mir-34a-5p and Clinical Association in Acute Ischemic Stroke Patients and in a Rat Model.

    PubMed

    Liang, Ting-Ying; Lou, Ji-Yu

    2016-01-01

    BACKGROUND MiRNA is widely recognized as the most important regulator in various diseases. However, there has been little research regarding miRNA expression and its involvement in ischemic stroke. MATERIAL AND METHODS In this study, we investigated the pattern of miRNA-34a-5p expression along with its clinical application in human ischemic stroke and in an in vivo rat model. We recruited 102 cerebral ischemia patients and 97 health controls for this study. Clinical data were gathered and recorded with the help of questionnaires. Blood samples were obtained from patients within 72 h after cerebral ischemia. National Institutes of Health Stroke Scale (NIHSS), Acute Stroke Treatment (TOAST), and infarct volume were used to analyze the correlation of miRNA-34a-5p expression and clinical information. In addition, blood samples and brain tissues were collected from an established middle cerebral artery occlusion (MCAO) model consisting of 20 adult male mice at 24 h after the MCAO. Expression level of miRNA-34a-5p was detected by real-time polymerase chain reactions. RESULTS Results showed overexpression of miRNA-34a-5p in acute ischemic stroke patients blood samples compared to the controls (p<0.05). Also, large and small arterial strokes types demonstrated elevated miRNA-34a-5p expression levels. Further correlation analysis revealed a negative association between miRNA-34a-5p and NIHSS scores (r=-0.692 p<0.05) and infarct volume (r=-0.719, p<0.05). Moreover, in vivo experiment results showed significant up-regulated expression of miRNA-34a-5p in middle cerebral artery occlusion compared to controls, along with a positive correlation between miRNA-34a-5p in blood and brain (r=0.742, p<0.05). CONCLUSIONS Our results suggest there is a potential regulatory role of miRNA-34a-5p in acute ischemic stroke, which could serve as a therapeutic target or biomarker in stroke prognosis. PMID:27545688

  16. Increased Expression of mir-34a-5p and Clinical Association in Acute Ischemic Stroke Patients and in a Rat Model

    PubMed Central

    Liang, Ting-ying; Lou, Ji-yu

    2016-01-01

    Background MiRNA is widely recognized as the most important regulator in various diseases. However, there has been little research regarding miRNA expression and its involvement in ischemic stroke. Material/Methods In this study, we investigated the pattern of miRNA-34a-5p expression along with its clinical application in human ischemic stroke and in an in vivo rat model. We recruited 102 cerebral ischemia patients and 97 health controls for this study. Clinical data were gathered and recorded with the help of questionnaires. Blood samples were obtained from patients within 72 h after cerebral ischemia. National Institutes of Health Stroke Scale (NIHSS), Acute Stroke Treatment (TOAST), and infarct volume were used to analyze the correlation of miRNA-34a-5p expression and clinical information. In addition, blood samples and brain tissues were collected from an established middle cerebral artery occlusion (MCAO) model consisting of 20 adult male mice at 24 h after the MCAO. Expression level of miRNA-34a-5p was detected by real-time polymerase chain reactions. Results Results showed overexpression of miRNA-34a-5p in acute ischemic stroke patients blood samples compared to the controls (p<0.05). Also, large and small arterial strokes types demonstrated elevated miRNA-34a-5p expression levels. Further correlation analysis revealed a negative association between miRNA-34a-5p and NIHSS scores (r=−0.692 p<0.05) and infarct volume (r=−0.719, p<0.05). Moreover, in vivo experiment results showed significant up-regulated expression of miRNA-34a-5p in middle cerebral artery occlusion compared to controls, along with a positive correlation between miRNA-34a-5p in blood and brain (r=0.742, p<0.05). Conclusions Our results suggest there is a potential regulatory role of miRNA-34a-5p in acute ischemic stroke, which could serve as a therapeutic target or biomarker in stroke prognosis. PMID:27545688

  17. Dynamic spatio-temporal imaging of early reflow in a neonatal rat stroke model

    PubMed Central

    Leger, Pierre-Louis; Bonnin, Philippe; Lacombe, Pierre; Couture-Lepetit, Elisabeth; Fau, Sebastien; Renolleau, Sylvain; Gharib, Abdallah; Baud, Olivier; Charriaut-Marlangue, Christiane

    2013-01-01

    The aim of the study was to better understand blood-flow changes in large arteries and microvessels during the first 15 minutes of reflow in a P7 rat model of arterial occlusion. Blood-flow changes were monitored by using ultrasound imaging with sequential Doppler recordings in internal carotid arteries (ICAs) and basilar trunk. Relative cerebral blood flow (rCBF) changes were obtained by using laser speckle Doppler monitoring. Tissue perfusion was measured with [14C]-iodoantipyrine autoradiography. Cerebral energy metabolism was evaluated by mitochondrial oxygen consumption. Gradual increase in mean blood-flow velocities illustrated a gradual perfusion during early reflow in both ICAs. On ischemia, the middle cerebral artery (MCA) territory presented a residual perfusion, whereas the caudal territory remained normally perfused. On reflow, speckle images showed a caudorostral propagation of reperfusion through anastomotic connections, and a reduced perfusion in the MCA territory. Autoradiography highlighted the caudorostral gradient, and persistent perfusion in ventral and medial regions. These blood-flow changes were accompanied by mitochondrial respiration impairment in the ipsilateral cortex. Collectively, these data indicate the presence of a primary collateral pathway through the circle of Willis, providing an immediate diversion of blood flow toward ischemic regions, and secondary efficient cortical anastomoses in the immature rat brain. PMID:23047273

  18. Ischemic Stroke

    MedlinePlus

    ... Spread the Word Advocate Share Spread the Word Contact Us Contact Us 1-800-STROKES (787-6537) 9707 E. ... Stroke En Espanol Stroke Facts Come Back Strong Contact Us 1-800-787-6537 9707 E. Easter ...

  19. Stroke Rehabilitation

    MedlinePlus

    A stroke can cause lasting brain damage. People who survive a stroke need to relearn skills they lose because of ... damage. Rehabilitation can help them relearn those skills. Stroke can cause five types of disabilities: Paralysis or ...

  20. Hemorrhagic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Hemorrhagic stroke is the less common type. It happens when ... an artery wall that breaks open. Symptoms of stroke are Sudden numbness or weakness of the face, ...

  1. Therapeutic benefits of combined treatment with tissue plasminogen activator and 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside in an animal model of ischemic stroke.

    PubMed

    Yu, Shu; Liu, Xin; Shen, Yuntian; Xu, Hui; Yang, Yumin; Ding, Fei

    2016-07-01

    Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke, but tPA therapy is limited by a short therapeutic window and some adverse side effects. 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside, a salidroside analog (code-named SalA-4g), has shown potent neuroprotective effects. In this study, a rat model of embolic middle cerebral artery occlusion (MCAO) was used to mimic ischemic stroke. The embolic MCAO rats were intravenously (iv) injected with tPA alone, SalA-4g alone, or a combination of tPA and SalA-4g. Compared to treatment with tPA alone at 4h post MCAO, combined treatment with tPA at 4h post MCAO and SalA-4g starting at 4h post MCAO and continuing for 3days at an interval of 24h significantly reduced neurological deficits and infarct volume, and significantly inhibited the intracerebral bleeding, edema formation, neuronal loss, and cellular apoptosis in the ischemic brain. Our results suggested that additive neuroprotective actions of SalA-4g contributed to widening the therapeutic window of tPA therapy and ameliorating its side effects in treating MCAO rats. The therapeutic benefits of combined treatment with tPA and SalA-4g for ischemic stroke might be associated with its effects on cerebral glucose metabolism. PMID:27060484

  2. Stroke genetics: a review and update.

    PubMed

    Lindgren, Arne

    2014-09-01

    Stroke genetics includes several topics of clinical interest, including (1) molecular genetic variations affecting risk of monogenic stroke syndromes; (2) molecular genetic variations affecting risk of common stroke syndromes, sometimes with specific effects on risk of specific main types of stroke or subtypes of ischemic and hemorrhagic stroke; (3) genetics of conditions associated with stroke risk e.g. white matter hyperintensities, atrial fibrillation and hypertension; (4) hereditary causes of familial aggregation of stroke; (5) epigenetic impact on protein expression during acute brain injury; (6) genetic influence on stroke recovery; and (7) pharmacogenetics. Genetic research methods include candidate gene studies; Genome Wide Association Studies; family studies; RNA and protein analyses; and advanced computer-aided analytical methods to detect statistically significant associations. Several methods that could improve our knowledge of stroke genetics are being developed e.g.: Exome content analysis; Next-generation sequencing; Whole genome sequencing; and Epigenetics. During 2012-2014, several Single Nucleotide Polymorphisms (SNPs) have been related to common ischemic stroke risk. Certain SNPs have been associated with risk of specific ischemic stroke subtypes such as large vessel disease and cardiac embolism, particular subtypes of intracerebral hemorrhage (ICH), especially lobar ICH, and with prognosis after ICH. Large international studies on stroke recovery and exome content are ongoing. Advanced mathematical models have been used to study how several SNPs can act together and increase stroke risk burden. Such efforts require large numbers of patients and controls, which is achieved by co-operation in large international consortia such as the International Stroke Genetics Consortium. This overview includes an introduction to genetics, stroke genetics in general, and different genetic variations that may influence stroke risk. It presents some of the latest

  3. Is Remodelling of Corticospinal Tract Terminations Originating in the Intact Hemisphere Associated with Recovery following Transient Ischaemic Stroke in the Rat?

    PubMed Central

    Mitchell, Emma J.; Dewar, Deborah; Maxwell, David J

    2016-01-01

    Following large strokes that encompass the cerebral cortex, it has been suggested that the corticospinal tract originating from the non-ischaemic hemisphere reorganises its pattern of terminal arborisation within the spinal cord to compensate for loss of function. However many strokes in humans predominantly affect subcortical structures with minimal involvement of the cerebral cortex. The aim of the present study was to determine whether remodelling of corticospinal terminals arising from the non-ischaemic hemisphere was associated with spontaneous recovery in rats with subcortical infarcts. Rats were subjected to transient middle cerebral artery occlusion or sham surgery and 28 days later, when animals exhibited functional recovery, cholera toxin b subunit was injected into the contralesional, intact forelimb motor cortex in order to anterogradely label terminals within cervical spinal cord segments. Infarcts were limited to subcortical structures and resulted in partial loss of corticospinal tract axons from the ischaemic hemisphere. Quantitative analysis revealed there was no significant difference in the numbers of terminals on the contralesional side of the spinal grey matter between ischaemic and sham rats. The results indicate that significant remodelling of the corticospinal tract from the non-ischaemic hemisphere is not associated with functional recovery in animals with subcortical infarcts. PMID:27014870

  4. Fatal pulmonary embolism in hospitalized patients: a large autopsy-based matched case-control study

    PubMed Central

    Carvalho Bricola, Solange Aparecida Petilo; Paiva, Edison Ferreira; Lichtenstein, Arnaldo; Gianini, Reinaldo José; Duarte, Jurandir Godoy; Shinjo, Samuel Katsuyuki; Eluf-Neto, Jose; Arruda Martins, Milton

    2013-01-01

    OBJECTIVE: Pulmonary embolism is an underdiagnosed major cause of death for hospitalized patients. The objective of this study was to identify the conditions associated with fatal pulmonary embolism in this population. METHODS: A total of 13,074 autopsy records were evaluated in a case-control study. Patients were matched by age, sex, and year of death, and factors potentially associated with fatal pulmonary embolism were analyzed using univariate and multivariate conditional logistic regression. RESULTS: Pulmonary embolism was considered fatal in 328 (2.5%) patients. In the multivariate analysis, conditions that were more common in patients who died of pulmonary embolism were atherosclerosis, congestive heart failure, and neurological surgery. Some conditions were negatively associated with fatal pulmonary embolism, including hemorrhagic stroke, aortic aneurism, cirrhosis, acquired immune deficiency syndrome, and pneumonia. In the control group, patients with hemorrhagic stroke and aortic aneurism had short hospital stays (8.5 and 8.8 days, respectively), and the hemorrhage itself was the main cause of death in most of them (90.6% and 68.4%, respectively), which may have prevented the development of pulmonary embolism. Cirrhotic patients in the control group also had short hospital stays (7 days), and 50% died from bleeding complications. CONCLUSIONS: In this large autopsy study, atherosclerosis, congestive heart failure, and neurological surgery were diagnoses associated with fatal pulmonary embolism. PMID:23778403

  5. Diagnosis, prognosis, and management of cryptogenic stroke

    PubMed Central

    Zhang, Cen; Kasner, Scott

    2016-01-01

    Despite many advances in our understanding of ischemic stroke, cryptogenic strokes (those that do not have a determined etiology) remain a diagnostic and therapeutic challenge. Previous classification approaches to cryptogenic stroke have led to inconsistent definitions, and evidence to determine optimal treatment is scarce. These limitations have prompted international efforts to redefine cryptogenic strokes, leading to more rigorous diagnostic criteria, outcome studies, and new clinical trials. Improvement in our ability to detect paroxysmal atrial fibrillation in patients with cryptogenic stroke has strengthened the idea that these strokes are embolic in nature. Further, better understanding of acute biomarkers has helped to identify otherwise occult mechanisms. Together, these strategies will inform long-term outcomes and shape management. PMID:26918178

  6. Anterior spinal cord infarction owing to possible fibrocartilaginous embolism.

    PubMed

    Raghavan, Ashok; Onikul, Ella; Ryan, Monique M; Prelog, Kristina; Taranath, Ajay; Chennapragada, Murthy

    2004-06-01

    Anterior spinal artery syndrome is characterised by acute flaccid quadriparesis or paraparesis, disturbance of pain and temperature sensation, and loss of sphincter control. Fibrocartilaginous embolism is a rarely recognised, but important cause of spinal cord infarction. Fibrocartilaginous embolisation usually occurs after minor trauma without major bony lesions, typically with an intervening symptom-free interval and progressive 'stroke-in-evolution' course. There is evidence that the embolus originates from the intervertebral disc, but the mechanism whereby disc fragments enter the spinal vessels is not well understood. We describe the evolution of MRI findings in a case of anterior spinal artery territory infarction thought to be secondary to fibrocartilaginous embolism. PMID:14747876

  7. Cryptogenic postpartum stroke.

    PubMed

    Bereczki, Dániel; Szegedi, Norbert; Szakács, Zoltán; Gubucz, István; May, Zsolt

    2016-01-01

    An estimated 25-40% of ischemic strokes are classified as cryptogenic, which means the cause of the cerebral infarction remains unidentified. One of the potential pathomechanisms - especially among young patients with no cardiovascular risk factors - is paradoxical embolism through a patent foramen ovale. Pregnancy, cesarean delivery and the postpartum period are associated with an increased risk of cerebrovascular events. Factors that may contribute to ischemic strokes during gestation and puerperium include classic cardiovascular risk factors, changes in hemostaseology/hemodynamics, and pregnancy-specific disorders such as pre-eclampsia, eclampsia, postpartum cerebral angiopathy or peripartum cardiomyopathy. In this case report, we present a 36-year-old thrombolysis candidate undergoing mechanical thrombectomy 3 weeks after a cesarean section due to HELLP-syndrome. After evaluation of anamnestic and diagnostic parameters, closure of the patent foramen ovale has been performed. In the absence of specific guidelines, diagnostic work-up for cryptogenic stroke should be oriented after the suspected pathomechanism based on patient history and clinical picture. As long as definite evidences emerge, management of cryptogenic stroke patients with pathogenic right-to-left shunt remains individual based on the mutual decision of the patient and the multidisciplinary medical team. PMID:27591063

  8. Chronic Brain Tissue Remodeling after Stroke in Rat: A One Year Multiparametric Magnetic Resonance Imaging Study

    PubMed Central

    Karki, Kishor; Knight, Robert A.; Shen, Li Hong; Kapke, Alissa; Lu, Mei; Li, Yi; Chopp, Michael

    2010-01-01

    Rats subjected to 2 hours of transient middle cerebral artery occlusion were studied temporally over 1 year by magnetic resonance imaging (MRI) and behavioral testing. Multiparameter MRI measures of T2, T1, T1 in the presence of off-resonance saturation of the bound proton signal (T1sat), apparent diffusion coefficient (ADC) and susceptibility-weighted imaging (SWI) were obtained at 1 day, 1, 2, 3 and 4 weeks, and 3, 6, 9 and 12 months post-ischemia. Regions of interest included: ischemic core (damaged both at 1 day and later); new lesion (normal at 1 day, but damaged later); and recovery (damaged at 1 day, but normal later) areas. Hematoxylin and eosin, Prussian blue and ED-1, a monoclonal antibody murine macrophage marker, stainings were performed for histological assessment. Core area T2 and ADC values increased until ~6 months, and T1 and T1sat until ~12 months. New lesion area MRI parameter values increased until ~6 months (T2, T1 and ADC), or ~1 year (T1sat). Lesion area was largest at 1 day (mean±SD: 37.0±13.7 mm2) and smallest at 1 year (18.1±10.5 mm2). Recovery area was largest at 3 weeks (8.9±3.8 mm2) and smallest at 1 year (6.4±3.3 mm2). The ipsilateral/contralateral ventricle area ratio was 0.7±0.2 at 1 day and increased significantly at 1 year (2.4±0.7). Iron-laden macrophages, histologically confirmed at 1 year, were detected in the lesion borders by SWI at 3, 6, 9 and 12 months. Our data indicate that MRI detectable changes of ischemia-damaged brain tissue continue for at least 1 year post-ischemia. PMID:20828544

  9. Foreign body pulmonary embolism.

    PubMed

    Rief, Peter; Belaj, Klara; Smaczny, Nicole; Augustin, Michael; Eller, Philipp; Brodmann, Marianne; Pilger, Ernst

    2013-06-01

    We report a case of a foreign body embolism caused by a tip of an explanted port-a-cath system. The embolus could be removed with a gooseneck snare catheter, the patient fully recovered. PMID:23765525

  10. Embolization of Brain Aneurysms and Fistulas

    MedlinePlus

    ... Professions Site Index A-Z Embolization of Brain Aneurysms and Arteriovenous Malformations/Fistulas Embolization of brain aneurysms ... Aneurysms and Fistulas? What is Embolization of Brain Aneurysms and Fistulas? Embolization of brain aneurysms and arteriovenous ...

  11. Interleukin-6 as an early marker for fat embolism

    PubMed Central

    Yoga, R; Theis, JC; Walton, M; Sutherland, W

    2009-01-01

    Background Fat Embolism is a complication of long bone fractures, intramedullary fixation and joint arthroplasty. It may progress to fat embolism syndrome, which is rare but involves significant morbidity and can occasionally be fatal. Fat Embolism can be detected at the time of embolization by transoesophageal echocardiography or atrial blood sampling. Later, a combination of clinical signs and symptoms will point towards fat embolism but there is no specific test to confirm the diagnosis. We investigated serum Interleukin-6 (IL-6) as a possible early marker for fat embolism. Methods An animal study was conducted to simulate a hip replacement in 31 adult male Sprague Dawley rats. The procedure was performed under general anesthesia and the animals divided into 3 groups: control, uncemented and cemented. Following surgery and recovery from anaesthesia, the rats allowed to freely mobilize in their cages. Blood was taken before surgery and at 6 hours, 12 hours and 24 hours to measure serum IL-6 levels. The rats were euthanized at 24 hours and lungs removed and stained for fat. The amount of fat seen was then correlated with serum IL-6 levels. Results No rats in the control group had fat emboli. Numerous fat emboli were seen in both the uncemented and cemented implant groups. The interleukin levels were raised in all groups reaching a peak at 12 hours after surgery reaching 100 pg/ml in the control group and around 250 pg/ml in the uncemented and cemented implant groups. The IL-6 levels in the control group were significantly lower than any of the implant groups at 12 and 24 hours. At these time points, the serum IL-6 correlated with the amount of fat seen on lung histology. Conclusion Serum IL-6 is a possible early marker of fat embolism. PMID:19523233

  12. MRI/SPECT/Fluorescent Tri-Modal Probe for Evaluating the Homing and Therapeutic Efficacy of Transplanted Mesenchymal Stem Cells in a Rat Ischemic Stroke Model

    PubMed Central

    Tang, Yaohui; Wang, Jixian; Lin, Xiaojie; Zhang, Lu; Yang, Yi; Wang, Yongting; Zhang, Zhijun; Bulte, Jeff W. M.

    2015-01-01

    Quantitatively tracking engraftment of intracerebrally or intravenously transplanted stem cells and evaluating their concomitant therapeutic efficacy for stroke has been a challenge in the field of stem cell therapy. In this study, first, an MRI/SPECT/fluorescent tri-modal probe (125I-fSiO4@SPIOs) is synthesized for quantitatively tracking mesenchymal stem cells (MSCs) transplanted intracerebrally or intravenously into stroke rats, and then the therapeutic efficacy of MSCs delivered by both routes and the possible mechanism of the therapy are evaluated. It is demonstrated that (125)I-fSiO4@SPIOs have high efficiency for labeling MSCs without affecting their viability, differentiation, and proliferation capacity, and found that 35% of intracerebrally injected MSCs migrate along the corpus callosum to the lesion area, while 90% of intravenously injected MSCs remain trapped in the lung at 14 days after MSC transplantation. However, neurobehavioral outcomes are significantly improved in both transplantation groups, which are accompanied by increases of vascular endothelial growth factor, basic fibroblast growth factor, and tissue inhibitor of metalloproteinases-3 in blood, lung, and brain tissue (p < 0.05). The study demonstrates that 125I-fSiO4@SPIOs are robust probe for long-term tracking of MSCs in the treatment of ischemic brain and MSCs delivered via both routes improve neurobehavioral outcomes in ischemic rats. PMID:26290659

  13. Arteriovenous Fistula Embolization in Suspected Parauterine Choriocarcinoma.

    PubMed

    Alturkistani, Husain; Almarzooqi, Mohamed-Karji; Oliva, Vincent; Gilbert, Patrick

    2016-01-01

    This is a case of choriocarcinoma that did not regress after chemotherapy treatment. A 30-year-old female patient (gravida 2, para 2), presented to our ER with stroke and persistent mild pelvic pain 2 months after a Caesarean section. Computed tomography (CT) revealed an ischemic left hemicerebellar region and a hypervascular mass in the pelvic region. This mass was not present on routine fetal ultrasound during pregnancy. The lesion was treated by chemotherapy after closure of a foramen ovale and insertion of an inferior vena cava (IVC) filter. After that, 2 courses of EMACO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, and Vincristine) chemotherapy regimen were given. Posttreatment CT showed the hypervascular mass without any changes. Arteriography showed the arteriovenous fistulae that were embolized successfully with plugs, coils, and glue. Embolization was considered due to the risk of acute hemorrhagic life-threatening complications. Eight chemotherapy courses were added after embolization. Treatment by endovascular approach and reduction of the hypervascular mass can be a valuable adjunct to chemotherapy treatment of choriocarcinoma. PMID:27403360

  14. Arteriovenous Fistula Embolization in Suspected Parauterine Choriocarcinoma

    PubMed Central

    Almarzooqi, Mohamed-Karji; Oliva, Vincent; Gilbert, Patrick

    2016-01-01

    This is a case of choriocarcinoma that did not regress after chemotherapy treatment. A 30-year-old female patient (gravida 2, para 2), presented to our ER with stroke and persistent mild pelvic pain 2 months after a Caesarean section. Computed tomography (CT) revealed an ischemic left hemicerebellar region and a hypervascular mass in the pelvic region. This mass was not present on routine fetal ultrasound during pregnancy. The lesion was treated by chemotherapy after closure of a foramen ovale and insertion of an inferior vena cava (IVC) filter. After that, 2 courses of EMACO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, and Vincristine) chemotherapy regimen were given. Posttreatment CT showed the hypervascular mass without any changes. Arteriography showed the arteriovenous fistulae that were embolized successfully with plugs, coils, and glue. Embolization was considered due to the risk of acute hemorrhagic life-threatening complications. Eight chemotherapy courses were added after embolization. Treatment by endovascular approach and reduction of the hypervascular mass can be a valuable adjunct to chemotherapy treatment of choriocarcinoma. PMID:27403360

  15. Stroke in the Lehigh Valley: racial/ethnic differences.

    PubMed

    Friday, G; Lai, S M; Alter, M; Sobel, E; LaRue, L; Gil-Peralta, A; McCoy, R L; Levitt, L P; Isack, T

    1989-09-01

    We investigated black/white differences in stroke rate (standardized morbidity), severity, and subtype, and the relative frequencies of 5 primary risk factors (hypertension, diabetes, myocardial infarction, other heart diseases, and transient ischemic attack [TIA]) using the Lehigh Valley Stroke Register. Blacks had a statistically significant higher, age-adjusted rate of stroke than whites. We found no differences in stroke severity using our measures but blacks had a statistically higher proportion of lacunar stroke, while whites had a higher proportion of embolic stroke. There were no differences in proportions of thrombotic stroke or intracerebral hemorrhage. The relative frequencies of hypertension, myocardial infarction, other heart diseases, and diabetes were higher for blacks, while the relative frequency of TIA was higher for whites. These observations are consistent with other reports that blacks have a higher frequency of stroke and tend to have more small-vessel cerebrovascular pathology than whites. PMID:2771065

  16. Paradoxical brain embolism associated with Kimura disease mimics watershed infarction.

    PubMed

    Tanaka, Yasutaka; Ueno, Yuji; Shimada, Yoshiaki; Yamashiro, Kazuo; Tanaka, Ryota; Urabe, Takao; Hattori, Nobutaka

    2015-02-01

    Kimura disease (KD) is an uncommon chronic inflammatory disease presenting as subcutaneous lymphadenopathy with eosinophilia. To date, only a single case of brain embolism caused by fibroblastic endocarditis associated with KD has been reported. Watershed infarction was seen in patients with episodes of severe hypotension or cardiac surgery. We here report a young case of KD who developed ischemic stroke and showed multiple small infarcts in the border zones between the territories of major cerebral arteries, mimicking watershed infarction. Transesophageal echocardiography revealed patent foramen ovale and atrial septal aneurysm. Concurrently, deep venous thrombus in the femoral vein was found on duplex ultrasonography. Our case supports the notion that paradoxical brain embolism associated with KD can cause multiple small embolisms and mimic watershed infarction. PMID:25447210

  17. Isolated asymptomatic pulmonary arteriovenous malformation presenting with ischaemic stroke.

    PubMed

    Bertram, Kelly L; Madan, Anoop; Frayne, Judith

    2016-07-01

    Young onset stroke is uncommon, and may be due to conditions other than traditional vascular risk factors. A 42-year-old woman with an ischaemic stroke was found to have left atrial bubble study positivity on transthoracic echocardiogram (TTE) suggestive of patent foramen ovale, however she also had low peripheral oxygen saturation. Investigation revealed an isolated pulmonary arteriovenous malformation (PAVM), visible on admission chest radiograph. This can cause embolic stroke and is an alternate cause of the TTE findings. The PAVM was able to be closed via endovascular intervention, removing the shunt and therefore removing her risk of recurrent stroke events. This is a rare cause of embolic stroke in young people which can be easily missed on investigation yet is amenable to treatment. PMID:26896908

  18. Tissue oxygen is reduced in white matter of spontaneously hypertensive-stroke prone rats: a longitudinal study with electron paramagnetic resonance.

    PubMed

    Weaver, John; Jalal, Fakhreya Y; Yang, Yi; Thompson, Jeffrey; Rosenberg, Gary A; Liu, Ke J

    2014-05-01

    Small vessel disease is associated with white-matter (WM) magnetic resonance imaging (MRI) hyperintensities (WMHs) in patients with vascular cognitive impairment (VCI) and subsequent damage to the WM. Although WM is vulnerable to hypoxic-ischemic injury and O₂ is critical in brain physiology, tissue O₂ level in the WM has not been measured and explored in vivo. We hypothesized that spontaneously hypertensive stroke-prone rat (SHR/SP) fed a Japanese permissive diet (JPD) and subjected to unilateral carotid artery occlusion (UCAO), a model to study VCI, would lead to reduced tissue oxygen (pO₂) in the deep WM. We tested this hypothesis by monitoring WM tissue pO₂ using in vivo electron paramagnetic resonance (EPR) oximetry in SHR/SP rats over weeks before and after JPD/UCAO. The SHR/SP rats experienced an increase in WM pO₂ from 9 to 12 weeks with a maximal 32% increase at week 12, followed by a dramatic decrease in WM pO₂ to near hypoxic conditions during weeks 13 to 16 after JPD/UCAO. The decreased WM pO₂ was accompanied with WM damage and hemorrhages surrounding microvessels. Our findings suggest that changes in WM pO₂ may contribute to WM damage in SHR/SP rat model, and that EPR oximetry can monitor brain pO₂ in the WM of small animals. PMID:24549186

  19. Pulmonary embolism and amniotic fluid embolism in pregnancy.

    PubMed

    Brennan, Matthew C; Moore, Lisa E

    2013-03-01

    Amniotic fluid embolism and pulmonary embolism are 2 of the most common causes of maternal mortality in the developed world. Symptoms of pulmonary embolism include tachycardia, tachypnea, and shortness of breath, all of which are common complaints in pregnancy. Heightened awareness leads to rapid diagnosis and institution of therapy. Amniotic fluid embolism is associated with maternal collapse. There are currently no proven therapies, although rapid initiation of supportive care may decrease the risk of mortality. PMID:23466134

  20. Radiation dosimetry of the fibrin-binding probe 64Cu-FBP8 and its feasibility for positron emission tomography imaging of deep vein thrombosis and pulmonary embolism in rats

    PubMed Central

    Blasi, Francesco; Oliveira, Bruno L; Rietz, Tyson A; Rotile, Nicholas J; Day, Helen; Naha, Pratap C; Cormode, David P; Izquierdo-Garcia, David; Catana, Ciprian; Caravan, Peter

    2016-01-01

    The diagnosis of deep venous thromboembolic disease is still challenging despite the progress of current thrombus imaging modalities and new diagnostic algorithms. We recently reported the high target uptake and thrombus imaging efficacy of the novel fibrin-specific positron emission tomography probe 64Cu-FBP8. Here, we tested the feasibility of 64Cu-FBP8-PET to detect source thrombi and culprit emboli after deep vein thrombosis and pulmonary embolism (DVT-PE). To support clinical translation of 64Cu-FBP8, we performed a human dosimetry estimation using time-dependent biodistribution in rats. Methods Sprague-Dawley rats (n=7) underwent ferric chloride application on the femoral vein to trigger thrombosis. Pulmonary embolism was induced 30 min or 2 days after deep vein thrombosis by intrajugular injection of a preformed blood clot labeled with 125I-Fibrinogen. PET imaging was performed to detect the clots, and single-photon emission tomography (SPECT) was used to confirm in vivo the location of the pulmonary emboli. Ex vivo gamma-counting and histopathology were used to validate the imaging findings. Detailed biodistribution was performed in healthy rats (n=30) at different time-points after 64Cu-FBP8 administration to estimate human radiation dosimetry. Longitudinal whole-body PET/MR imaging (n=2) was performed after 64Cu-FBP8 administration to further assess radioactivity clearance. Results 64Cu-FBP8-PET imaging detected the location of lung emboli and venous thrombi after DVT-PE, revealing significant differences in uptake between target and background tissues (P<0.001). In vivo SPECT imaging and ex vivo gamma-counting confirmed the location of the lung emboli. PET quantification of the venous thrombi revealed that probe uptake was greater in younger clots than in older ones, a result confirmed by ex vivo analyses (P<0.001). Histopathology revealed an age-dependent reduction of thrombus fibrin content (P=0.006), further supporting the imaging findings

  1. Atrial fibrillation and stroke: epidemiology.

    PubMed

    Reiffel, James A

    2014-04-01

    The statistics for AFib are impressive. (online video available at: http://education.amjmed.com/video.php?event_id=445&stage_id=5&vcs=1). The principal risk with AFib, stroke or thrombotic embolism, is increased 5-fold in some series; AFib accounts for ≥15% of all strokes in the United States, 36% of strokes for individuals aged >80, and up to 20% of cryptogenic strokes, which means >100,000-125,000 embolic strokes per year, of which >20% are fatal. Patients with ischemic stroke and AFib are significantly (P<.0005) more likely to be chronically disabled, bedridden, and to require constant nursing care, particularly older patients (≥85 years). Prevention of these thromboembolic outcomes requires prophylactic anticoagulation therapy. The "gold standard" for anticoagulation has been warfarin, despite its well-known side effects and adherence challenges for patients. The recent approvals of several new, novel oral anticoagulation (NOAC) agents, however, presents physicians with a benefit/risk profile that represents an important advance over warfarin prophylaxis. The principal risk with all oral anticoagulants is bleeding. An important misconception about warfarin is that if anticoagulated patients bleed, the risk can be quickly reversed, but most trial experience has found that warfarin reversal requires 24 hours to halve the INR value. Reversal of anticoagulation with the NOACs is unproven at present; possible approaches are presented in this review, but since the NOACs have both rapid onsets of action and short biologic half-lives, they do not present the same reversal challenges as warfarin. Finally, physicians must be aware of thromboembolic risk assessment. The principal risk assessment scores are CHADS2, updated with the more recent CHA2DS2-VASc to provide more accurate assessment of low-risk patients; this review concludes with a novel flow-chart showing physicians how the CHADS2/CHA2DS2-VASc scoring systems can be used. PMID:24655742

  2. Functional Improvement after Photothrombotic Stroke in Rats Is Associated with Different Patterns of Dendritic Plasticity after G-CSF Treatment and G-CSF Treatment Combined with Concomitant or Sequential Constraint-Induced Movement Therapy

    PubMed Central

    Leukel, Petra; Bauer, Henrike; Schäbitz, Wolf-Rüdiger; Sommer, Clemens J.; Minnerup, Jens

    2016-01-01

    We have previously shown that granulocyte-colony stimulating factor (G-CSF) treatment alone, or in combination with constraint movement therapy (CIMT) either sequentially or concomitantly, results in significantly improved sensorimotor recovery after photothrombotic stroke in rats in comparison to untreated control animals. CIMT alone did not result in any significant differences compared to the control group (Diederich et al., Stroke, 2012;43:185–192). Using a subset of rat brains from this former experiment the present study was designed to evaluate whether dendritic plasticity would parallel improved functional outcomes. Five treatment groups were analyzed (n = 6 each) (i) ischemic control (saline); (ii) CIMT (CIMT between post-stroke days 2 and 11); (iii) G-CSF (10 μg/kg G-CSF daily between post-stroke days 2 and 11); (iv) combined concurrent group (CIMT plus G-CSF) and (v) combined sequential group (CIMT between post-stroke days 2 and 11; 10 μg/kg G-CSF daily between post-stroke days 12 and 21, respectively). After impregnation of rat brains with a modified Golgi-Cox protocol layer V pyramidal neurons in the peri-infarct cortex as well as the corresponding contralateral cortex were analyzed. Surprisingly, animals with a similar degree of behavioral recovery exhibited quite different patterns of dendritic plasticity in both peri-lesional and contralesional areas. The cause for these patterns is not easily to explain but puts the simple assumption that increased dendritic complexity after stroke necessarily results in increased functional outcome into perspective. PMID:26752421

  3. Functional Improvement after Photothrombotic Stroke in Rats Is Associated with Different Patterns of Dendritic Plasticity after G-CSF Treatment and G-CSF Treatment Combined with Concomitant or Sequential Constraint-Induced Movement Therapy.

    PubMed

    Frauenknecht, Katrin; Diederich, Kai; Leukel, Petra; Bauer, Henrike; Schäbitz, Wolf-Rüdiger; Sommer, Clemens J; Minnerup, Jens

    2016-01-01

    We have previously shown that granulocyte-colony stimulating factor (G-CSF) treatment alone, or in combination with constraint movement therapy (CIMT) either sequentially or concomitantly, results in significantly improved sensorimotor recovery after photothrombotic stroke in rats in comparison to untreated control animals. CIMT alone did not result in any significant differences compared to the control group (Diederich et al., Stroke, 2012;43:185-192). Using a subset of rat brains from this former experiment the present study was designed to evaluate whether dendritic plasticity would parallel improved functional outcomes. Five treatment groups were analyzed (n = 6 each) (i) ischemic control (saline); (ii) CIMT (CIMT between post-stroke days 2 and 11); (iii) G-CSF (10 μg/kg G-CSF daily between post-stroke days 2 and 11); (iv) combined concurrent group (CIMT plus G-CSF) and (v) combined sequential group (CIMT between post-stroke days 2 and 11; 10 μg/kg G-CSF daily between post-stroke days 12 and 21, respectively). After impregnation of rat brains with a modified Golgi-Cox protocol layer V pyramidal neurons in the peri-infarct cortex as well as the corresponding contralateral cortex were analyzed. Surprisingly, animals with a similar degree of behavioral recovery exhibited quite different patterns of dendritic plasticity in both peri-lesional and contralesional areas. The cause for these patterns is not easily to explain but puts the simple assumption that increased dendritic complexity after stroke necessarily results in increased functional outcome into perspective. PMID:26752421

  4. [Cerebellar stroke].

    PubMed

    Paradowski, Michał; Zimny, Anna; Paradowski, Bogusław

    2015-01-01

    Cerebellar stroke belongs to a group of rare diseases of vascular origin. Cerebellum, supplied by three pairs of arteries (AICA, PICA, SCA) with many anastomoses between them is less susceptible for a stroke, especially ischemic one. Diagnosis of the stroke in this region is harder due to lower sensibility of commonly used CT of the head in case of stroke suspicion. The authors highlight clinical symptoms distinguishing between vascular territories or topographical locations of the stroke, diagnostic procedures, classical and surgical treatment, the most common misdiagnoses are also mentioned. The authors suggest a diagnostic and therapeutic algorithm development, including rtPA treatment criteria for ischemic cerebellar stroke. PMID:26181157

  5. Bipyridine, an iron chelator, does not lessen intracerebral iron-induced damage or improve outcome after intracerebral hemorrhagic stroke in rats.

    PubMed

    Caliaperumal, Jayalakshmi; Wowk, Shannon; Jones, Sarah; Ma, Yonglie; Colbourne, Frederick

    2013-12-01

    Iron chelators, such as the intracellular ferrous chelator 2,2'-bipyridine, are a potential means of ameliorating iron-induced injury after intracerebral hemorrhage (ICH). We evaluated bipyridine against the collagenase and whole-blood ICH models and a simplified model of iron-induced damage involving a striatal injection of FeCl2 in adult rats. First, we assessed whether bipyridine (25 mg/kg beginning 12 h post-ICH and every 12 h for 3 days) would attenuate non-heme iron levels in the brain and lessen behavioral impairments (neurological deficit scale, corner turn test, and horizontal ladder) 7 days after collagenase-induced ICH. Second, we evaluated bipyridine (20 mg/kg beginning 6 h post-ICH and then every 24 h) on edema 3 days after collagenase infusion. Body temperature was continually recorded in a subset of these rats beginning 24 h prior to ICH until euthanasia. Third, bipyridine was administered (as per experiment 2) after whole-blood infusion to examine tissue loss, neuronal degeneration, and behavioral impairments at 7 days post-stroke, as well as body temperature for 3 days post-stroke. Finally, we evaluated whether bipyridine (25 mg/kg given 2 h prior to surgery and then every 12 h for 3 days) lessens tissue loss, neuronal death, and behavioral deficits after striatal FeCl2 injection. Bipyridine caused a significant hypothermic effect (maximum drop to 34.6 °C for 2-5 h after each injection) in both ICH models; however, in all experiments bipyridine-treated rats were indistinguishable from vehicle controls on all other measures (e.g., tissue loss, behavioral impairments, etc.). These results do not support the use of bipyridine against ICH. PMID:24323426

  6. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists

    PubMed Central

    Lip, Gregory Y.H.; Rasmussen, Lars H.; Olsson, S. Bertil; Jensen, Eva C.; Persson, Anders L.; Eriksson, Ulf; Wåhlander, Karin F.C.

    2009-01-01

    Aims Oral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, is a prodrug converted to a selective and reversible direct thrombin inhibitor (AR-H067637). We report from a Phase II randomized, dose-guiding study (NCT00684307) to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of extended-release AZD0837 in patients with AF. Methods and results Atrial fibrillation patients (n = 955) with ≥1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2–3, target 2.5) for 3–9 months. Approximately 30% of patients were naïve to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3–14.7%, mean exposure 138–145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). d-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naïve subjects with treatment, whereas in VKA pre-treated patients, d-dimer levels started low and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by ∼10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase ≥3× upper limit of normal was similar for AZD0837 and VKA. Conclusion AZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA. This study is

  7. Association between changes in weight and cerebral arteries in rats.

    PubMed

    Divani, Afshin A; Patel, Ankur; Fredrickson, Vance L; Siljander, Blake; Vazquez, Gabriela

    2010-06-01

    The objective of the study was to gain a better understanding of brain artery diameters and anatomical variations for precise modification of cerebral blood supply in ischemic stroke models. Sprague-Dawley rats (n = 35) were used for the experiment. Rats were perfused and resin replicas of cerebral arteries were created using a corrosion casting technique. Resin replicas were measured and analyzed for correlation of vessel lumen with animal sex and weight. A strong correlation between root of aorta diameter and weight was observed (p < 0.0001). We also observed a significant correlation between weight, internal carotid arteries, right external carotid artery, and pterygopalatine arteries. For the common carotid artery, a significant difference between the left and right branches was observed even though there was no association with weight. There was no significant association observed between animal sex and vessel size independent of weight. A better knowledge of vessel lumen in relation to animal sex and weight is essential for adequate blockage of an intracranial artery to induce cerebral ischemia in a rat model of stroke. This study provides a viable reference for choice of rat size in relation to the size of embolic agents such as filaments, microwires, or in vitro thrombus used in ischemic stroke experiments. PMID:24323492

  8. Stroke Rehabilitation

    MedlinePlus

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  9. Stroke Stories

    MedlinePlus

    ... this page please turn Javascript on. Feature: Stroke Rehabilitation Stroke Stories Past Issues / Spring 2013 Table of ... she has returned to an active life after rehabilitation. Tedy Bruschi: The New England Patriots linebacker was ...

  10. Preventing stroke

    MedlinePlus

    ... Partially-hydrogenated or hydrogenated fats Medical problems may lead to stroke Control your cholesterol and diabetes with ... increase the chance of blood clots, which can lead to stroke. Clots are more likely in women ...