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  1. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

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    Jun Li

    Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

  2. Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

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    Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

    2018-04-01

    Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for

  3. Induction of interleukin-1β mRNA after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M.; Sauter, A.; Boddeke, H.W.G.M.

    1994-01-01

    The expression of interleukin-1β (IL-1β) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery (MCAO).

  4. INDUCTION OF INTERLEUKIN-1-BETA MESSENGER-RNA AFTER FOCAL CEREBRAL-ISCHEMIA IN THE RAT

    NARCIS (Netherlands)

    BUTTINI, M; SAUTER, A; BODDEKE, HWGM

    The expression of interleukin-1beta (IL-1beta) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery

  5. Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M; Appel, K; Sauter, A; GebickeHaerter, PJ; Boddeke, HWGM

    Induction of tumor necrosis factor alpha was studied in the brain of rats after focal cerebral ischaemia by occlusion of the left middle cerebral artery. Using a specific antisense riboprobe for in situ hybridization histochemistry, cells positive for tumor necrosis factor alpha messenger RNA were

  6. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent...

  7. Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

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    Xin, Nian; Yang, Fang-Ju; Li, Yan; Li, Yu-Juan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Deng, Yu-Lin

    2013-12-15

    Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (ppills had protective effects on focal cerebral ischemia rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

  8. Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia.

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    Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

    2013-06-10

    The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. In the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h' middle cerebral artery occlusion (MCAO) followed by 24 h' reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments. Our study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.

  9. [Focal cerebral ischemia in rats with estrogen deficiency and endothelial dysfunction].

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    Litvinov, A A; Volotova, E V; Kurkin, D V; Logvinova, E O; Darmanyan, A P; Tyurenkov, I N

    2017-01-01

    To assess an effect of ovariectomy (OE) on the cerebral blood flow, endothelium-dependent vasodilation, neurological, cognitive and locomotor deficit as markers of brain damage after focal ischemia in rats. The study was conducted in 48 female Wistar rats. Ovariectomy was performed with ovaries and uterine body extirpation, cerebral ischemia was performed by middle cerebral artery occlusion (MCAO) in rats. To assess brain damage, Combs and Garcia scores, 'open field' test (OFT), 'extrapolatory escape test' (EET), 'passive avoidance test' (PAT), 'beam-walking test' were used. Cerebral blood flow was measured using ultrasonic flowmetry. After 7 days of MCAO, the cerebral blood flow in ovarioectomized animals was reduced by 20% compared to sham-ovariectomized animals. Ovariectomized animals with MCAO showed a three-fold endothelium-dependent vasodilation reduction (the reaction of cerebral vessels to the introduction of acetylcholine and N-L-arginine), indicating the presence of severe endothelial dysfunction. In ovarioectomized animals, the cerebral blood flow was reduced by 34% compared to sham-operated animals. MCAO and OE taken together resulted in more than 2-fold increase in neurological, motor disturbances, 3-fold decrease in motor activity of the animals in the OP test. Focal ischemia in ovarioectomized animals with endothelial dysfunction led to memory decrease by 1/5 fold in PAT and by 2-fold in EET.

  10. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

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    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L.

    2016-01-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases

  11. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

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    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L. [Department of Neurology, Shenzhen Hospital, Peking University, Shenzhen (China)

    2016-08-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

  12. Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats

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    Song, Xue; Xu, Rui; Xie, Fei; Zhu, Haiyuan; Zhu, Ji; Wang, Xin

    2014-01-01

    Objective: To investigate the inducible effect of hemin on exogenous neuroglobin (Ngb) in focal cerebral hypoxic-ischemia in rats. Methods: 125 healthy SD rats were randomly divided into five groups: sham-operation control group, operation group, hemin treatment group, exogenous Ngb treatment group, and hemin and exogenous Ngb joint treatment group. Twenty-four hours after focal cerebral hypoxic-ischemia, Ngb expression was evaluated by immunocytochemistry, RT-PCR, and western blot analyses, while the brain water content and infarct volume were examined. Results: Immunocytochemistry, RT-PCR, and western blot analyses showed more pronounced Ngb expression in the hemin and exogenous Ngb joint operation group than in the hemin or exogenous Ngb individual treatment groups, thus producing significant differences in brain water content and infarct volume (p exogenous Ngb. PMID:24966924

  13. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

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    Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

    2011-01-01

    Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

  14. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

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    Jintanaporn Wattanathorn

    2011-01-01

    Full Text Available Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO. Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

  15. Sequential changes in ischemic edema following transient focal cerebral ischemia in rats; Magnetic resonance imaging study

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    Nagahiro, Shinji; Goto, Satoshi; Kogo, Kasei; Sumi, Minako; Takahashi, Mutsumasa; Ushio, Yukitaka [Kumamoto Univ. (Japan). School of Medicine

    1994-07-01

    Sequential and regional changes in ischemic edema following various durations of focal cerebral ischemia were studied by magnetic resonance (MR) imaging in a rat unilateral intraluminal middle cerebral artery occlusion model. Occlusion was performed from 5 minutes to 5 hours. T[sub 2]-weighted images were obtained chronologically 6 hours after onset of ischemia, on day 1 and day 7. An immunohistochemical study using antibodies to calcineurin and glial fibrillary acidic protein was performed to observe histological changes in the ischemic brain. The T[sub 2] high-signal-intensity areas representing ischemic edema were observed in the lateral striatum and/or the cerebral cortex by day 1 in all rats with 1- to 5-hour ischemia, and the areas were larger and detected earlier with longer durations of ischemia. In three of six rats with 15-minute ischemia and five of six rats with 30-minute ischemia, the T[sub 2] high-signal-intensity areas appeared transiently on day 1 in the dorsolateral striatum where loss of neurons expressing calcineurin immunoreactivity and associated gliosis were found. MR imaging in animal models of reversible focal ischemia can achieve sequential and noninvasive evaluation of dynamic regional changes in ischemic edema. (author).

  16. Effects of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats

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    Mingsan Miao

    2017-05-01

    Full Text Available The effect of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats was observed. The model group, nimodipine group, cerebral collateral group, and large, medium and small dose group of the Rabdosia rubescens total flavonoids were administered with corresponding drugs but sham operation group and model group were administered the same volume of 0.5%CMC, 1 times a day, continuous administration of 7 d. After 1 h at 7 d to medicine, left incision in the middle of the neck of rats after anesthesia, we can firstly expose and isolate the left common carotid artery (CCA, and then expose external carotid artery (ECA and internal carotid artery (ICA. The common carotid artery and the external carotid artery are ligated. Then internal carotid artery with arterial clamp is temporarily clipped. Besides, cut the incision of 0.2 mm from 5 cm of the bifurcation of the common carotid artery. A thread Line bolt is inserted with more than 18–20 mm from bifurcation of CCA into the internal carotid artery until there is resistance. Then the entrance of the middle cerebral artery is blocked and internal carotid artery is ligated (the blank group only exposed the left blood vessel without Plugging wire. Finally it is gently pulled out the plug line after 2 h. Results: Compared with the model mice, Rabdosia rubescens total flavonoids can significantly relieve the injury of brain in hippocampus and cortex nerve cells; experimental rat focal cerebral ischemia was to improve again perfusion model of nerve function defect score mortality; significantly reduce brain homogenate NOS activity and no content, MDA, IL-1, TNF-a, ICAM-1 content; increase in brain homogenate SOD and ATPase activity (P < 0.05, P < 0.01; and reduce the serum S-100β protein content. Each dose group of the Rabdosia rubescens total flavonoids has a better Improvement effect on focal cerebral ischemia reperfusion model in rats.

  17. Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia

    OpenAIRE

    Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

    2015-01-01

    Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potent...

  18. The neuroprotective efficacy of MK-801 in focal cerebral ischemia varies with rat strain and vendor.

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    Oliff, H S; Marek, P; Miyazaki, B; Weber, E

    1996-08-26

    The present study was designed to evaluate whether the neuroprotective efficacy of MK-801 in focal cerebral ischemia was dependent on strain and/or vendor differences. MK-801 (0.12 mg/kg i.v. bolus followed by 0.108 mg/kg/h infusion or 0.60 mg/kg i.v. bolus followed by 0.540 mg/kg/h infusion) or saline was administered just after intraluminal middle cerebral artery occlusion. Administration of 0.540 mg/kg/h MK-801 provided strain/line-dependent neuroprotection in the following rank order: Simonsen Laboratories Sprague-Dawley rats > Simonsen Laboratories Wistar rats > Taconic Laboratories Sprague-Dawley rats. After 0.108 mg/kg/h MK-801 treatment, Simonsen Laboratories Wistar rats were the only strain/line that were significantly neuroprotected. These results indicate that the neuroprotective effect of an experimental drug may be influenced by rat strain and vendor differences.

  19. Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia.

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    Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

    2015-01-01

    Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potential molecular mechanisms in cerebral ischemia rats. We found that sulforaphane significantly attenuated the blood-brain barrier (BBB) disruption; decreased the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β; reduced the nitric oxide (NO) levels and inducible nitric oxide synthase (iNOS) activity; inhibited the expression of iNOS and cyclooxygenase-2 (COX-2). In addition, sulforaphane inhibits the expression of p-NF-κB p65 after focal cerebral ischemia-reperfusion injury. Taken together, our results suggest that sulforaphane suppresses the inflammatory response via inhibiting the NF-κB signaling pathway in a rat model of focal cerebral ischemia, and sulforaphane may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

  20. Expression of Neurotrophin-3 and trkC following Focal Cerebral Ischemia in Adult Rat Brain with Treadmill Exercise

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    Jin-Young Chung

    2017-01-01

    Full Text Available Neurotrophin-3 (NT-3 is a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC receptor. NT-3 has been shown to have neuroprotective effects in focal cerebral ischemia. Exercise also has ability to induce functional recovery in focal cerebral ischemia. However, the relationship between NT-3, its receptor trkC, and exercise has not been revealed. In this study, we assessed the expressions of NT-3 and trkC in focal cerebral ischemia. We also assessed the expression of NT-3 and trkC with treadmill exercise in focal cerebral ischemia. The results showed that, in a permanent middle cerebral artery occlusion rat model, exercise increased NT-3 and trkC expression. However, the patterns of expression of NT-3 and trkC at different time points varied. These results suggest that exercise-induced functional recovery in focal cerebral ischemia was related to NT-3 and trkC, but the role on times of NT-3 and trkC differed, although trkC is the receptor kinase for NT-3.

  1. [Adipose-derived stem cell transplantation promotes the expression of netrin-1 in the rat cortex after focal cerebral ischemia].

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    Wang, Jiehua; Hong, Zhuquan; Pan, Ying; Li, Guoqian

    2017-01-01

    Objective To observe the effect of adipose-derived stem cells (ADSCs) transplantation on the expression of netrin-1 in rats after focal cerebral ischemia. Methods Male SD rats were randomly divided into control group, model group and ADSC group. ADSCs were harvested and purified. Focal cerebral ischemia models were established in rats by the suture method. ADSCs were injected into the lateral ventricle of ADSC group rats and the same does of PBS was given to model group rats. At day 4, 7 and 14 after reperfusion, six rats were sacrificed to remove the brain tissues at each time point. The expression of netrin-1 was detected by reverse-transcription PCR, Western blotting and immunohistochemistry. Results Compared with the control group, the expression of netrin-1 in the brain tissues of the model group increased after focal cerebral ischemia, reached the peak at 4 days, and the expression of netrin-1 was significantly higher than that of the control group at each time point. Compared with the model group, the expression of netrin-1 in the ADSC group increased further, reached the peak at 7 days, and the expression of netrin-1 in the ADSC group was significantly higher than that of the model group at each time point. Conclusion ADSC transplantation could up-regulate the expression of netrin-1, and promote axon regeneration and the recovery of neurological functions.

  2. Effect of tetramethylpyrazine on the spatial learning and memory function of rats after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Jianjun Zhao; Yong Liu; Xinlin Chen; Jianxin Liu; Yingfang Tian; Pengbo Zhang; Qianyan Kang; Fen Qiu

    2006-01-01

    BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arterial resistance, increases cerebral blood flow, and improves microcirculation.OBJECTIVE: To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN: A randomized controlled trial.SETTING: Department of Human Anatomy and Histological Embryology, School of Medicine, Xi'an Jiaotong University.MATERIALS: Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi'an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co. Ltd (Lot Number: 2004051106, Specification: 2 mL/piece).METHODS: The experiments were carried out in School of Medicine of Xi'an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method: sham-operated group, cerebral ischemia control group, Iow-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections.MAIN OUTCOME MEASURES: The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed,RESULTS : Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the

  3. Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats

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    Xin-juan Li

    2015-01-01

    Full Text Available The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X 7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X 7 receptors.

  4. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep

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    Wolfgang Härtig

    2017-08-01

    Full Text Available As part of the extracellular matrix (ECM, perineuronal nets (PNs are polyanionic, chondroitin sulfate proteoglycan (CSPG-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU, their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a mice after filament-based permanent middle cerebral artery occlusion (pMCAO; (b rats subjected to thromboembolic MACO; and (c sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV. Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the

  5. Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia

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    Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

    2013-01-01

    Background The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. Results I...

  6. Neuroprotective effect of curcumin on transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Zhao, Jing; Zhao, Yong; Zheng, Weiping; Lu, Yuyu; Feng, Gang; Yu, Shanshan

    2008-09-10

    Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from the powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Hence, in the present study the neuroprotective potential of curcumin was investigated in middle cerebral artery occlusion (MCAO) induced focal cerebral IR injury. Administration of curcumin 100 and 300 mg/kg i.p. 60 min after MCAO significantly diminished infarct volume, and improved neurological deficit in a dose-dependent manner. Nissl staining showed that the neuronal injury was significantly improved after being treated with curcumin. Curcumin significantly decreased the expression of caspase-3 protein. A higher number of TUNEL-positive cells were found in the vehicle group, but they were significantly decreased in the treated group. Taken together, these results suggest that the neuroprotective potentials of curcumin against focal cerebral ischemic injury are, at least in part, ascribed to its anti-apoptotic effects.

  7. Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.

    Science.gov (United States)

    Jia, Jie; Zhang, Xi; Hu, Yong-Shan; Wu, Yi; Wang, Qing-Zhi; Li, Na-Na; Wu, Cai-Qin; Yu, Hui-Xian; Guo, Qing-Chuan

    2009-03-01

    Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion. Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration. Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.

  8. Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation.

    Science.gov (United States)

    Fan, Tao; Jiang, Wei Long; Zhu, Jian; Feng Zhang, Yu

    2012-01-01

    Stroke is the third leading cause of death in industrialized countries and the most important cause of acquired adult disability. Many evidences suggest that inflammation accounts for the progression of cerebral ischemic injury. Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignin isolated from certain plants, has shown anti-inflammatory activity against diabetes and Alzheimer's disease. In this study, we tested whether arctigenin can protect middle cerebral artery occluded (MCAO) rats. Male Sprague-Dawley rats were pretreated with arctigenin or vehicle for 7 d before being subjected to transient occlusion of middle cerebral artery and reperfusion. Rats were evaluated at 24 h after MCAO for neurological deficit scoring. Furthermore, the mechanism of the anti-inflammatory effect of arctigenin was investigated with a focus on inflammatory cells, proinflammatory cytokines, and transcriptional factors. Arctigenin significantly reduced cerebral infarction and improved neurological outcome. Arctigenin suppressed the activation of microglia and decreased the expression of interleukin (IL)- 1β and tumor necrosis factor (TNF)-α. These results revealed that arctigenin has a promising therapeutic effect in ischemic stroke treatment through an anti-inflammatory mechanism.

  9. Chronic photoperiod disruption does not increase vulnerability to focal cerebral ischemia in young normotensive rats.

    Science.gov (United States)

    Ku Mohd Noor, Ku Mastura; Wyse, Cathy; Roy, Lisa A; Biello, Stephany M; McCabe, Christopher; Dewar, Deborah

    2017-11-01

    Photoperiod disruption, which occurs during shift work, is associated with changes in metabolism or physiology (e.g. hypertension and hyperglycaemia) that have the potential to adversely affect stroke outcome. We sought to investigate if photoperiod disruption affects vulnerability to stroke by determining the impact of photoperiod disruption on infarct size following permanent middle cerebral artery occlusion. Adult male Wistar rats (210-290 g) were housed singly under two different light/dark cycle conditions ( n = 12 each). Controls were maintained on a standard 12:12 light/dark cycle for nine weeks. For rats exposed to photoperiod disruption, every three days for nine weeks, the lights were switched on 6 h earlier than in the previous photoperiod. T 2 -weighted magnetic resonance imaging was performed at 48 h after middle cerebral artery occlusion. Disruption of photoperiod in young healthy rats for nine weeks did not alter key physiological variables that can impact on ischaemic damage, e.g. blood pressure and blood glucose immediately prior to middle cerebral artery occlusion. There was no effect of photoperiod disruption on infarct size after middle cerebral artery occlusion. We conclude that any potentially adverse effect of photoperiod disruption on stroke outcome may require additional factors such as high fat/high sugar diet or pre-existing co-morbidities.

  10. Improvement in regional CBF by L-serine contributes to its neuroprotective effect in rats after focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Tao-Jie Ren

    Full Text Available To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF. Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1 reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2 improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3 increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca(2+-activated K(+ channels on the cerebral blood vessel endothelium.

  11. Progesterone induces neuroprotection following reperfusion-promoted mitochondrial dysfunction after focal cerebral ischemia in rats.

    Science.gov (United States)

    Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

    2017-06-01

    Organelle damage and increases in mitochondrial permeabilization are key events in the development of cerebral ischemic tissue injury because they cause both modifications in ATP turnover and cellular apoptosis/necrosis. Early restoration of blood flow and improvement of mitochondrial function might reverse the situation and help in recovery following an onset of stroke. Mitochondria and related bioenergetic processes can be effectively used as pharmacological targets. Progesterone (P4), one of the promising neurosteroids, has been found to be neuroprotective in various models of neurological diseases, through a number of mechanisms. This influenced us to investigate the possible role of P4 in the mitochondria-mediated neuroprotective mechanism in an ischemic stroke model of rat. In this study, we have shown the positive effect of P4 administration on behavioral deficits and mitochondrial health in an ischemic stroke injury model of transient middle cerebral artery occlusion (tMCAO). After induction of tMCAO, the rats received an initial intraperitoneal injection of P4 (8 mg/kg body weight) or vehicle at 1 h post-occlusion followed by subcutaneous injections at 6, 12 and 18 h. Behavioral assessment for functional deficits included grip strength, motor coordination and gait analysis. Findings revealed a significant improvement with P4 treatment in tMCAO animals. Staining of isolated brain slices from P4-treated rats with 2,3,5-triphenyltetrazolium chloride (TTC) showed a reduction in the infarct area in comparison to the vehicle group, indicating the presence of an increased number of viable mitochondria. P4 treatment was also able to attenuate mitochondrial reactive oxygen species (ROS) production, as well as block the mitochondrial permeability transition pore (mPTP), in the tMCAO injury model. In addition, it was also able to ameliorate the altered mitochondrial membrane potential and respiration ratio in the ischemic animals, thereby suggesting that P4 has

  12. Protective Effects of Dihydrocaffeic Acid, a Coffee Component Metabolite, on a Focal Cerebral Ischemia Rat Model

    Directory of Open Access Journals (Sweden)

    Kyungjin Lee

    2015-06-01

    Full Text Available We recently reported the protective effects of chlorogenic acid (CGA in a transient middle cerebral artery occlusion (tMCAo rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p. dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema.

  13. Mild focal cerebral ischemia in the rat. The effect of local temperature on infarct size

    DEFF Research Database (Denmark)

    Hildebrandt-Eriksen, Elisabeth S; Christensen, Thomas; Diemer, Nils Henrik

    2002-01-01

    . The effect of local temperature at the occlusion site in this model was furthermore tested. Thirty-three Wistar rats were subjected to 30 min of simultaneous common carotid artery and distal middle cerebral artery occlusion or sham treatment. Animals were magnetic resonance-scanned repeatedly between day one...... and day 14 after surgery, then sacrificed, and paraffin brain sections stained. All animals scanned 24 h after reperfusion showed an area of edema in the affected cortex, which later was identified as an infarct. Animals with a temperature of 33.9 +/- 1.5 degrees C at the MCA site (hypothermic) showed...... smaller infarcts (14.4 +/- 10 mm3) than animals with normothermic local temperature (36.7 +/- 0.2 degrees C, 57.7 +/- 26.4 mm3). Infarct size was maximal on day 3 after ischemia but decreased as edema subsided. Infarct volumes from histology and magnetic resonance imaging correlated well. The model...

  14. Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

    Science.gov (United States)

    Haghnejad Azar, Adel; Oryan, Shahrbanoo; Bohlooli, Shahab; Panahpour, Hamdollah

    2017-01-01

    This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats. Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods. Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively). Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity. © 2016 S. Karger AG, Basel.

  15. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery.

    Science.gov (United States)

    Zhang, Shao-jie; Ke, Zheng; Li, Le; Yip, Shea-ping; Tong, Kai-yu

    2013-04-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely correlated with the neural

  16. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery

    International Nuclear Information System (INIS)

    Zhang, Shao-jie; Ke, Zheng; Tong, Kai-yu; Li, Le; Yip, Shea-ping

    2013-01-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague–Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely

  17. Effect of different component ratio of Astragalus total saponins and Verbena total glycosides on the cerebral infarction area and serum biochemical indicators in the focal cerebral ischemia-reperfusion rat model

    Directory of Open Access Journals (Sweden)

    Erping Xu

    2017-05-01

    Full Text Available Our purpose is to study the effect of different component ratio of Astragalus Total Saponins (ATS and Verbena Total Glycosides (VTG on the cerebral infarction area and the serum biochemical indicators in the focal cerebral ischemia-reperfusion rat model. Compared with the model group, different component ratio of ATS and VTG could significantly improve the neurological deficit scores to the focal cerebral ischemia-reperfusion rat model, and the group of 7:3, 6:4, 5:5 got the best results; it could reduce the mortality of rat model to a certain extent, and the group of 5:5 group got the best results; it can significantly reduce the cerebral infarction area, and the group of 7:3, 5:5, 4:6 got the best results; it could significantly reduce the content of TNF-α, and the group of 8:2, 6:4 got the best results; it could significantly reduce the content of NO, and the group of 7:3, 5:5 got the best results; it could significantly increase the content of SOD, and the group of 6:4, 5:5 got the best results. This indicates that different component ratio of ATS and VTG may protect the damage of focal cerebral ischemia-reperfusion rat model to a certain extent, which are compared using the comprehensive weight method and the ratio of 5:5 was proved to be the optimal active ratio.

  18. Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats

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    Shevtsov MA

    2014-05-01

    Full Text Available Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Anatolii V Dobrodumov,4 Anastasiy S Dayneko,5 Alexey A Shmonin,5,6 Timur D Vlasov,5 Elena V Melnikova,5 Alexander D Vilisov,4,5 Irina V Guzhova,1 Alexander M Ischenko,3 Anastasiya L Mikhrina,7 Oleg V Galibin,5 Igor V Yakovenko,2 Boris A Margulis1 1Institute of Cytology of the Russian Academy of Sciences (RAS, St Petersburg, Russia; 2AL Polenov Russian Research Scientific Institute of Neurosurgery, St Petersburg, Russia; 3Research Institute of Highly Pure Biopreparations, St Petersburg, Russia; 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS, St Petersburg, Russia; 5First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia; 6Federal Almazov Medical Research Centre, St Petersburg, Russia; 7IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS, St Petersburg, Russia Abstract: Recombinant 70 kDa heat shock protein (Hsp70 is an antiapoptotic protein that has a cell protective activity in stress stimuli and thus could be a useful therapeutic agent in the management of patients with acute ischemic stroke. The neuroprotective and neurotherapeutic activity of recombinant Hsp70 was explored in a model of experimental stroke in rats. Ischemia was produced by the occlusion of the middle cerebral artery for 45 minutes. To assess its neuroprotective capacity, Hsp70, at various concentrations, was intravenously injected 20 minutes prior to ischemia. Forty-eight hours after ischemia, rats were sacrificed and brain tissue sections were stained with 2% triphenyl tetrazolium chloride. Preliminary treatment with Hsp70 significantly reduced the ischemic zone (optimal response at 2.5 mg/kg. To assess Hsp70’s neurotherapeutic activity, we intravenously administered Hsp70 via the tail vein 2 hours after reperfusion (2 hours and 45 minutes after ischemia. Rats were then kept alive for 72 hours. The

  19. Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.

    Science.gov (United States)

    Yan, Han; Mitschelen, Matthew; Toth, Peter; Ashpole, Nicole M; Farley, Julie A; Hodges, Erik L; Warrington, Junie P; Han, Song; Fung, Kar-Ming; Csiszar, Anna; Ungvari, Zoltan; Sonntag, William E

    2014-11-01

    Aging is a major risk factor for cerebrovascular disease. Growth hormone (GH) and its anabolic mediator, insulin-like growth factor (IGF)-1, decrease with advancing age and this decline has been shown to promote vascular dysfunction. In addition, lower GH/IGF-1 levels are associated with higher stroke mortality in humans. These results suggest that decreased GH/IGF-1 level is an important factor in increased risk of cerebrovascular diseases. This study was designed to assess whether GH/IGF-1-deficiency influences the outcome of cerebral ischemia. We found that endothelin-1-induced middle cerebral artery occlusion resulted in a modest but nonsignificant decrease in cerebral infarct size in GH/IGF-1 deficient dw/dw rats compared with control heterozygous littermates and dw/dw rats with early-life GH treatment. Expression of endothelin receptors and endothelin-1-induced constriction of the middle cerebral arteries were similar in the three experimental groups. Interestingly, dw/dw rats exhibited reduced brain edema and less astrocytic infiltration compared with their heterozygous littermates and this effect was reversed by GH-treatment. Because reactive astrocytes are critical for the regulation of poststroke inflammatory processes, maintenance of the blood-brain barrier and neural repair, further studies are warranted to determine the long-term functional consequences of decreased astrocytic activation in GH/IGF-1 deficient animals after cerebral ischemia. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

  20. Reduction of mitochondrial electron transport complex activity is restricted to the ischemic focus after transient focal cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Christensen, Thomas; Diemer, Nils Henrik

    2003-01-01

    Using histochemical methods offering high topographical resolution for evaluation of changes in the ischemic focus and the penumbra, the mitochondrial electron transport chain (ETC) complexes I, II, and IV were examined in rats subjected to 2 h of proximal occlusion of the middle cerebral artery...

  1. Effects of Electroacupuncture Combined with Repetitive Transcranial Magnetic Stimulation on the Expression of Nestin in Neural Stem Cell after Focal Cerebral Ischemia in Adult Rats

    Institute of Scientific and Technical Information of China (English)

    HUANG Guofu; HUANG Xiaolin; CHEN Hong; HAY Xiaohua

    2009-01-01

    Objective: To investigate the influence of electroacupuncture (EA) combined with repetitive transeranial magnetic stimulation(rTMS) on the temporal profile of nestin expression after induction of focal cerebral isehemia in adult rats and to explore the mechanism of EA combined with rTMS in treating ischemic brain injury. Method: The model of transient focal ischemia was produced by occlusion of middle cerebral artery. Seventy-five Wistar rats were randomly divided into normal group, model group, EA group, rTMS group and EA +rTMS group. The neurologic impairment rating and ability of learning and memory were observed at the 7th、14th and 28th d after infarction respectively. Meanwhile, Western blotting was used to observe the number of nestin expression positive cells. Result: Nestin-positive cells were found in cortex, subgranular zone (SGZ), subventricular zone (SVZ) of the ipsilateral side at different time points after cerebral isehemia. The number of nestin-positive cells peaked at the 7th d, began to decrease at the 14th d and was significantly higher in EA+rTMS group than that in model group (P<0.05), then almost reached normal at the 28th d. The improvement of neural motor function deficits as well as the indexes of learning and memory were more obvious in EA+rTMS group compared with model group (P<0.01, P<0.05). These effects were most obvious in EA+rTMS group compared with the EA and rTMS group (P<0.05). Conclusion: EA and rTMS possess the potency of building up and can increase the number of nestin-positive cells in some brain regions after focal cerebral ischemia, which might be one of the important mechanisms of EA combined with rTMS in treating ischemia brain injury.

  2. PI3K/Akt Pathway Contributes to Neurovascular Unit Protection of Xiao-Xu-Ming Decoction against Focal Cerebral Ischemia and Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Rui Lan

    2013-01-01

    Full Text Available In the present study, we used a focal cerebral ischemia and reperfusion rat model to investigate the protective effects of Xiao-Xu-Ming decoction (XXMD on neurovascular unit and to examine the role of PI3K (phosphatidylinositol 3-kinase/Akt pathway in this protection. The cerebral ischemia was induced by 90 min of middle cerebral artery occlusion. Cerebral infarct area was measured by tetrazolium staining, and neurological function was observed at 24 h after reperfusion. DNA fragmentation assay, combined with immunofluorescence, was performed to evaluate apoptosis of neuron, astrocyte, and vascular endothelial cell which constitute neurovascular unit. The expression levels of proteins involved in PI3K/Akt pathway were detected by Western blot. The results showed that XXMD improved neurological function, decreased cerebral infarct area and neuronal damage, and attenuated cellular apoptosis in neurovascular unit, while these effects were abolished by inhibition of PI3K/Akt with LY294002. We also found that XXMD upregulated p-PDKl, p-Akt, and p-GSK3β expression levels, which were partly reversed by LY294002. In addition, the increases of p-PTEN and p-c-Raf expression levels on which LY294002 had no effect were also observed in response to XXMD treatment. The data indicated the protective effects of XXMD on neurovascular unit partly through the activation of PI3K/Akt pathway.

  3. Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on focal cerebral ischemia/reperfusion-induced inflammation, oxidative stress, and apoptosis in rats.

    Directory of Open Access Journals (Sweden)

    Gu Gong

    Full Text Available AIM: Glycyrrhizin (GL has been reported to protect against ischemia and reperfusion (I/R-induced injury by inhibiting the cytokine activity of high mobility group box 1 (HMGB1. In the present study, the protective effects of GL against I/R injury, as well as the related molecular mechanisms, were investigated in rat brains. METHODS: Focal cerebral I/R injury was induced by intraluminal filamentous occlusion of the middle cerebral artery (MCA in Male Sprague-Dawley rats. GL alone or GL and rHMGB1 were administered intravenously at the time of reperfusion. Serum levels of HMGB1 and inflammatory mediators were quantified via enzyme-linked immunosorbent assay (ELISA. Histopathological examination, immunofluorescence, RT-PCR and western blotting analyses were performed to investigate the protective and anti-apoptotic effects and related molecular mechanisms of GL against I/R injury in rat brains. RESULTS: Pre-treatment with GL significantly reduced infarct volume and improved the accompanying neurological deficits in locomotor function. The release of HMGB1 from the cerebral cortex into the serum was inhibited by GL administration. Moreover, pre-treatment with GL alleviated apoptotic injury resulting from cerebral I/R through the inhibition of cytochrome C release and caspase 3 activity. The expression levels of inflammation- and oxidative stress-related molecules including TNF-α, iNOS, IL-1β, and IL-6, which were over-expressed in I/R, were decreased by GL. P38 and P-JNK signalling were involved in this process. All of the protective effects of GL could be reversed by rHMGB1 administration. CONCLUSIONS: GL has a protective effect on ischemia-reperfusion injury in rat brains through the inhibition of inflammation, oxidative stress and apoptotic injury by antagonising the cytokine activity of HMGB1.

  4. Double-tracer autoradiographic study of protein synthesis and glucose consumption in rats with focal cerebral ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas; Balchen, T; Bruhn, T

    1999-01-01

    A double-tracer autoradiographic method for simultaneous measurement of regional glucose utilization (rCMRglc) and regional protein synthesis (PS) in consecutive brain sections is described and applied to study the metabolism of the ischemic penumbra 2 h after occlusion of the middle cerebral...... artery (MCAO) in rats. In halothane anesthesia, the left middle cerebral artery was permanently occluded. Two hours after MCAO an i.v. bolus injection of 14C-deoxyglucose and 3H-leucine was given and circulated for 45 min. Two sets of brain sections were processed for quantitative autoradiography....... Neighboring brain sections exposed an X-ray film (3H-insensitive), and a 3H-sensitive for determination of rCMRglc and PS, respectively. Sections for PS determination were washed in trichloroacetic acid (TCA) prior to film exposure in order to remove 14C-deoxyglucose and unincorporated 3H-leucine. Regional...

  5. Reduced PBR/TSPO Expression After Minocycline Treatment in a Rat Model of Focal Cerebral Ischemia: A PET Study Using [18F]DPA-714

    International Nuclear Information System (INIS)

    Martin, A.; Boisgard, R.; Tavitian, B.; Kassiou, M.; Dolle, F.

    2011-01-01

    Background: Many new candidate pharmaceuticals designed to improve recovery after stroke have been proposed recently, but there are still too few molecular imaging methods capable to assess their efficacy. A hallmark of the inflammatory reaction that follows focal cerebral ischemia is overexpression of the mitochondrial peripheral benzodiazepine receptor/18 kDa translocator protein (PBR/TSPO) in the monocytic lineage and astrocytes. This overexpression can be imaged with positron emission tomography (PET) using PBR/TSPO-selective radioligands such as [ 18 F]DPA-714. Purpose: Here, we tested whether PET with [ 18 F]DPA-714 would evidence the effect of minocycline, a broad spectrum antibiotic presently tested as neuro-protective agent after stroke, on the inflammatory reaction induced in an experimental model of stroke. Procedures: Ten rats were subjected to a 2-h transient middle cerebral artery occlusion with reperfusion. Minocycline or saline was intravenously administrated 1 h after reperfusion and daily during the following 6 days. PET studies were performed using [ 18 F]DPA-714 at 7 days after cerebral ischemia. Results: In vivo PET imaging showed a significant decrease in [ 18 F]DPA-714 uptake at 7 days after cerebral ischemia in rats treated with minocycline with respect to saline-treated animals. Minocycline treatment had no effect on the size of the infarcted area. Conclusion: Minocycline administered daily during 7 days after ischemia decreases [ 18 F]DPA- 714 binding, suggesting that the drug exerts an anti-inflammatory activity. [ 18 F]DPA-714 PET is a useful bio-marker to study novel anti-inflammatory strategies in experimental cerebral ischemia. (authors)

  6. Electroacupuncture modulates stromal cell-derived factor-1α expression and mobilization of bone marrow endothelial progenitor cells in focal cerebral ischemia/reperfusion model rats.

    Science.gov (United States)

    Xie, Chenchen; Gao, Xiang; Luo, Yong; Pang, Yueshan; Li, Man

    2016-10-01

    Stromal cell-derived factor-1α(SDF-1α) plays a crucial role in regulating the mobilization, migration and homing of endothelial progenitor cells(EPCs). Electroacupuncture(EA), a modern version of Traditional Chinese Medicine, can improve neurological recovery and angiogenesis in cerebral ischemic area. This study aimed to investigate the effects of electroacupuncture(EA) on the mobilization and migration of bone marrow EPCs and neurological functional recovery in rats model after focal cerebral ischemia/reperfusion and the potentially involved mechanisms. Sprague-Dawley rats received filament occlusion of the right middle cerebral artery for 2h followed by reperfusion for 12h, 1d, 2d, 3d, 7d respectively. Rats were randomly divided into sham group, model group and EA group. After 2h of the reperfusion, EA was given at the "Baihui" (GV 20)/Siguan ("Hegu" (LI 4)/"Taichong" (LR 3)) acupoints in the EA group. Modified neurological severity score (mNSS) was used to assess the neurological functional recovery. EPCs number and SDF-1α level in bone marrow(BM) and peripheral blood(PB) were detected by using fluorescence-activated cell sorting (FACS) analysis and quantitative real time polymerase chain reaction (qRT-PCR) respectively. An mNSS test showed that EA treatment significantly improved the neurological functional outcome. EPCs number in PB and BM were obviously increased in the EA group. After cerebral ischemia, the SDF-1α level was decreased in BM while it was increased in PB, which implied a gradient of SDF-1α among BM and PB after ischemia. It suggested that the forming of SDF-1α concentration gradient can induce the mobilization and homing of EPCs. Eletroacupuncture as a treatment can accelerate and increase the forming of SDF-1α concentration gradient to further induce the mobilization of EPCs and angiogenesis in ischemic brain and improve the neurological function recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Acute treatment with docosahexaenoic acid complexed to albumin reduces injury after a permanent focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Tiffany N Eady

    Full Text Available Docosahexaenoic acid complexed to albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo, but whether a similar effect occurs in permanent MCAo is unknown. Male Sprague-Dawley rats (270-330 g underwent permanent MCAo. Neurological function was evaluated on days 1, 2 and 3 after MCAo. We studied six groups: DHA (5 mg/kg, Alb (0.63 or 1.25 g/kg, DHA-Alb (5 mg/kg+0.63 g/kg or 5 mg/kg+1.25 g/kg or saline. Treatment was administered i.v. at 3 h after onset of stroke (n = 7-10 per group. Ex vivo imaging of brains and histopathology were conducted on day 3. Saline- and Alb-treated rats developed severe neurological deficits but were not significantly different from one another. In contrast, rats treated with low and moderate doses of DHA-Alb showed improved neurological score compared to corresponding Alb groups on days 2 and 3. Total, cortical and subcortical lesion volumes computed from T2 weighted images were reduced following a moderate dose of DHA-Alb (1.25 g/kg by 25%, 22%, 34%, respectively, compared to the Alb group. The total corrected, cortical and subcortical infarct volumes were reduced by low (by 36-40% and moderate doses (by 34-42% of DHA-Alb treatment compared to the Alb groups. In conclusion, DHA-Alb therapy is highly neuroprotective in permanent MCAo in rats. This treatment can provide the basis for future therapeutics for patients suffering from ischemic stroke.

  8. Talampanel improves the functional deficit after transient focal cerebral ischemia in rats. A 30-day follow up study.

    Science.gov (United States)

    Erdo, Franciska; Berzsenyi, Pál; Német, László; Andrási, Ferenc

    2006-01-15

    The neuroprotective effect of talampanel, a negative allosteric modulator of alpha-amino-3-hydroxy-methyl-4-isoxazolyl-propionic acid (AMPA) receptors has been described previously. However, in these studies the histological changes and not the functional consequences of the brain damage were evaluated. The aim of present investigation was to analyze the sensorimotor function after stroke and to test the influence of talampanel (GYKI-53773, LY-300164) by 30-day monitoring in rats. After 1h middle cerebral artery occlusion (MCAO) general 'well-being', neurological status, spontaneous motor activity, rotation, motor coordination, balancing, muscle strength and reaction time were followed for 1 month. Talampanel (6 x 10 mg/kg i.p. given on the day of stroke) improved the motor coordination in rotarod (p beam walking (p tests, reduced the number of stroke-induced rotations (p < 0.05), shortened the reflex time on the forelimb contralateral to brain ischemia and improved the survival rate comparing with vehicle treated control. After stroke, serious sensorimotor deficits appeared in rats but they showed partial spontaneous recovery after 30 days. Talampanel treatment enhanced the rate of functional improvement without changing the morphology at the end of the experiment. Our results indicate that modulation of AMPA receptors by talampanel can be a promising therapeutic approach to the treatment of stroke.

  9. GlyT1 Inhibitor NFPS Exerts Neuroprotection via GlyR Alpha1 Subunit in the Rat Model of Transient Focal Cerebral Ischaemia and Reperfusion

    Directory of Open Access Journals (Sweden)

    Baosheng Huang

    2016-05-01

    Full Text Available Background/Aims: Glycine is a strychnine-sensitive inhibitory neurotransmitter in the central nervous system (CNS, especially in the spinal cord, brainstem, and retina. The objective of the present study was to investigate the potential neuroprotective effects of GlyT1 inhibitor N [3-(4'-fluorophenyl-3-(4'-phenylphenoxy propyl] sarcosine (NFPS in the rat model of experimental stroke. Methods: In vivo ischaemia was induced by transient middle cerebral artery occlusion (tMCAO. The methods of Western Blotting, Nissl Staining and Morris water maze methods were applied to analyze the anti-ischaemia mechanism. Results: The results showed that high dose of NFPS (H-NFPS significantly reduced infarct volume, neuronal injury and the expression of cleaved caspase-3, enhanced Bcl-2/Bax, and improved spatial learning deficits which were administered three hours after transient middle cerebral artery occlusion (tMCAO induction in rats, while, low dose of NFPS (L-NFPS exacerbated the injury of ischaemia. These findings suggested that low and high dose of NFPS produced opposite effects. Importantly, it was demonstrated that H-NFPS-dependent neuronal protection was inverted by salicylate (Sal, a specific GlyR ɑ1 antagonist. Such effects could probably be attributed to the enhanced glycine level in both synaptic and extrasynaptic clefts and the subsequently altered extrasynaptic GlyRs and their subtypes. Conclusions: These data imply that GlyT1 inhibitor NFPS may be a novel target for clinical treatment of transient focal cerebral ischaemia and reperfusion which are associated with altered GlyR alpha 1 subunits.

  10. Serial neuroradiological studies in focal cerebritis

    International Nuclear Information System (INIS)

    Hatta, S.; Mochizuki, H.; Kuru, Y.; Miwa, H.; Kondo, T.; Mori, H.; Mizuno, Y.

    1994-01-01

    We report serial neuroradiological studies in a patient with focal cerebritis in the head of the left caudate nucleus. On the day after the onset of symptoms, CT showed an ill-defined low density lesion. The lack of contrast enhancement appeared to be the most important finding for differentiating focal cerebritis from an encapsulated brain abscess or a tumour. MRI two days later revealed the centre of the lesion to be of slightly low intensity on T1-weighted inversion recovery (IR) images and very low intensity on T2-weighted spin echo images, which appeared to correspond to the early cerebritis stage of experimentally induced cerebritis and brain abscess. Ten days after the onset of symptoms, CT revealed a thin ring of enhancement in the head of the caudate nucleus, and a similar small ring was seen in the hypothalamus 16 days after the onset, corresponding to the late cerebritis stage. MRI nine days later revealed ill-defined high signal lesions within the involved area on the T1-weighted IR images. To our knowledge, this is the first published MRI documentation of the early cerebritis stage developing into an encapsulated brain abscess. The mechanisms underlying of these radiographic changes are discussed. (orig.)

  11. Detection of viable cortical neurons using benzodiazepine receptor imaging after reversible focal ischaemia in rats: comparison with regional cerebral blood flow

    International Nuclear Information System (INIS)

    Watanabe, Yoshiyuki; Nakano, Takayuki; Yutani, Kenji; Nishimura, Hiroshi; Nishimura, Tsunehiko; Kusuoka, Hideo; Nakamura, Hironobu

    2000-01-01

    To elucidate the utility of benzodiazepine receptor imaging for the detection of viable cortical neurons, dual-tracer autoradiography using iodine-125 iomazenil (IMZ) and iodine-123 N-isopropyl-4-iodoamphetamine (IMP) was performed in a model of reversible focal ischaemia during the acute and subacute phases. The right middle cerebral artery of anaesthetized rats was occluded for 60 min using an intraluminal filament and reperfused. In the acute phase study, 125 I-IMZ (370 kBq) was injected via the femoral vein at 2 h after reperfusion, and 123 I-IMP (37 MBq) was injected at 50 min post-injection. Rats were sacrificed 10 min after the injection of 123 I-IMP. In the subacute phase study, the same procedure was performed at 5 days after reperfusion. In the acute phase, the IMP uptake was significantly decreased in almost all areas of the lesioned hemisphere, an exception being the cerebellum; however, the IMZ uptake was significantly decreased only in ischaemic cores. The discrepancy between IMZ and IMP uptake was observed in the lateral neocortex and the lateral caudate putamen (CPu), which were most frequently damaged in this ischaemic model. In the subacute phase, the IMZ uptake in lesioned rats was significantly decreased only in the parietal lobe and hippocampus, though the IMP uptake was decreased in many regions of lesioned hemispheres (the frontal, parietal cortex, CPu, hippocampus and thalamus). Histopathological findings indicated that both the IMP and the IMZ uptake was markedly decreased in necrotic areas. Although the IMP uptake was significantly decreased in the ischaemic areas, the IMZ uptake was maintained in these areas. These results suggest that benzodiazepine receptor imaging is superior to regional cerebral blood flow imaging for the detection of viable cortical neurons in both the acute and subacute phases of ischaemia. (orig.)

  12. Detection of viable cortical neurons using benzodiazepine receptor imaging after reversible focal ischaemia in rats: comparison with regional cerebral blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Yoshiyuki [Dept. of Radiology, Osaka National Hospital (Japan); Nakano, Takayuki; Yutani, Kenji; Nishimura, Hiroshi; Nishimura, Tsunehiko [Div. of Tracer Kinetics, Osaka University Medical School (Japan); Kusuoka, Hideo [Clinical Research Institute, Osaka National Hospital (Japan); Nakamura, Hironobu [Dept. of Radiology, Osaka University Medical School (Japan)

    2000-03-01

    To elucidate the utility of benzodiazepine receptor imaging for the detection of viable cortical neurons, dual-tracer autoradiography using iodine-125 iomazenil (IMZ) and iodine-123 N-isopropyl-4-iodoamphetamine (IMP) was performed in a model of reversible focal ischaemia during the acute and subacute phases. The right middle cerebral artery of anaesthetized rats was occluded for 60 min using an intraluminal filament and reperfused. In the acute phase study, {sup 125}I-IMZ (370 kBq) was injected via the femoral vein at 2 h after reperfusion, and {sup 123}I-IMP (37 MBq) was injected at 50 min post-injection. Rats were sacrificed 10 min after the injection of {sup 123}I-IMP. In the subacute phase study, the same procedure was performed at 5 days after reperfusion. In the acute phase, the IMP uptake was significantly decreased in almost all areas of the lesioned hemisphere, an exception being the cerebellum; however, the IMZ uptake was significantly decreased only in ischaemic cores. The discrepancy between IMZ and IMP uptake was observed in the lateral neocortex and the lateral caudate putamen (CPu), which were most frequently damaged in this ischaemic model. In the subacute phase, the IMZ uptake in lesioned rats was significantly decreased only in the parietal lobe and hippocampus, though the IMP uptake was decreased in many regions of lesioned hemispheres (the frontal, parietal cortex, CPu, hippocampus and thalamus). Histopathological findings indicated that both the IMP and the IMZ uptake was markedly decreased in necrotic areas. Although the IMP uptake was significantly decreased in the ischaemic areas, the IMZ uptake was maintained in these areas. These results suggest that benzodiazepine receptor imaging is superior to regional cerebral blood flow imaging for the detection of viable cortical neurons in both the acute and subacute phases of ischaemia. (orig.)

  13. The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study.

    Directory of Open Access Journals (Sweden)

    Ching-Chung Liang

    Full Text Available Human umbilical cord blood derived CD34+ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34+ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34+ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO. Experiment 2 was to evaluate the adjuvant effect of 17β-estradiol on CD34+ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34+ cells before MCAO (pre-treatment caused less infarction size than those infused after MCAO (post-treatment on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34+ + estradiol pre-treatment. When compared with no treatment group, CD34+ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34+ + estradiol pre-treatment. The present study suggests pre-treatment with CD34+ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF.

  14. Radiologic manifestations of focal cerebral hyperemia in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Skriver, E B; Herning, M

    1991-01-01

    In 16 acute stroke patients with focal cerebral hyperemia angiography and regional cerebral blood flow (rCBF) were studied 1 to 4 days post stroke. CT was performed twice with and without contrast enhancement 3 +/- 1 days and 16 +/- 4 days post stroke. Angiographic evidence of focal cerebral hype...

  15. Neuroprotective effect of STAZN, a novel azulenyl nitrone antioxidant, in focal cerebral ischemia in rats: dose-response and therapeutic window

    Science.gov (United States)

    Ley, James J.; Belayev, Ludmila; Saul, Isabel; Becker, David A.; Ginsberg., Myron D.

    2007-01-01

    Stilbazulenyl nitrone (STAZN) is a potent antioxidant that, in a rat model of transient focal cerebral ischemia, confers significant enduring functional and morphological neuroprotection. This study investigated the influence of dose and time of administration on the neuroprotective effects of STAZN in the intraluminal-suture model of middle cerebral artery occlusion (MCAo). Dose-Response At 2 and 4h after the onset of MCAo, animals received intravenously either STAZN (low dose=0.07 mg/kg, n=8), (medium dose=0.7 mg/kg, n=9), (high dose=3.5 mg/kg, n=9), an equivalent volume of vehicle (30% Solutol HS15 and 70% isotonic saline, 0.37 ml/kg, n=5), or saline (0.37 ml/kg, n=5). Only the medium dose improved scores (p<0.05) on a standardized neurobehavioral test at 1, 2 and 3d after MCAo. Only the medium dose reduced the total infarction (51%, p=0.014) compared to controls. These results indicate that STAZN exhibits maximal neuroprotection at the 0.7 mg/kg dose. Therapeutic Window STAZN (0.6 mg/kg) dissolved in dimethylsulfoxide was given intra-peritoneally at 2 and 4h (n=11), 3 and 5h (n=10), 4 and 6h (n=10), or 5 and 7h (n=7) after the onset of MCAo. Additional doses were given at 24 and 48h. Vehicle (dimethylsulfoxide, 2.0 ml/kg, n=6) was administered at 3, 5, 24 and 48h. STAZN treatment initiated at 2 or 3h after the onset of MCAo improved neurological scores (p<0.001) and reduced total infarction (42.2%, p<0.05) compared to controls. PMID:17945201

  16. Nonhuman primate models of focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Jingjing Fan

    2017-01-01

    Full Text Available Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

  17. Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Liu, Shimin; Shi, Honglian; Liu, Wenlan; Furuichi, Takamitsu; Timmins, Graham S; Liu, Ke Jian

    2004-03-01

    Stroke causes heterogeneous changes in tissue oxygenation, with a region of decreased blood flow, the penumbra, surrounding a severely damaged ischemic core. Treatment of acute ischemic stroke aims to save this penumbra before its irreversible damage by continued ischemia. However, effective treatment remains elusive due to incomplete understanding of processes leading to penumbral death. While oxygenation is central in ischemic neuronal death, it is unclear exactly what actual changes occur in interstitial oxygen tension (pO2) in ischemic regions during stroke, particularly the penumbra. Using the unique capability of in vivo electron paramagnetic resonance (EPR) oximetry to measure localized interstitial pO2, we measured both absolute values, and temporal changes of pO2 in ischemic penumbra and core during ischemia and reperfusion in a rat model. Ischemia rapidly decreased interstitial pO2 to 32% +/- 7.6% and 4% +/- 0.6% of pre-ischemic values in penumbra and core, respectively 1 hour after ischemia. Importantly, whilst reperfusion restored core pO2 close to its pre-ischemic value, penumbral pO2 only partially recovered. Hyperoxic treatment significantly increased penumbral pO2 during ischemia, but not in the core, and also increased penumbral pO2 during reperfusion. These divergent, important changes in pO2 in penumbra and core were explained by combined differences in cellular oxygen consumption rates and microcirculation conditions. We therefore demonstrate that interstitial pO2 in penumbra and core is differentially affected during ischemia and reperfusion, providing new insights to the pathophysiology of stroke. The results support normobaric hyperoxia as a potential early intervention to save penumbral tissue in acute ischemic stroke.

  18. Effect of NMDA Receptor Antagonist on Local Cerebral Glucose Metabolic Rate in Focal Cerebral Ischemia

    International Nuclear Information System (INIS)

    Kim, Sang Eun; Hong, Seung Bong; Yoon, Byung Woo

    1995-01-01

    There has recently been increasing interest in the use of NMDA receptor antagonists as potential neuroprotective agents for the treatment of ischemic stroke. To evaluate the neuroprotective effect of the selective non-competitive NMDA receptor antagonist MK-801 in focal cerebral ischemia, local cerebral glucose utilization (1CGU) was examined in 15 neuroanatomically discrete regions of the conscious rat brain using the 2-deoxy-D[14C]glucose quantitative autoradiographic technique 24 hr after left middle cerebral artery occlusion (MCAO). Animals received MK-801 (5 mg/kg i.v.) or saline vehicle before (20-30 min) or after (30 min) MCAO. Both pretreatment and posttreatment of MK-801 increased occluded/non-occluded 1CGU ratio in 7 and 5 of the 15 regions measured, respectively(most notably in cortical structures). Following MK-801 pretreatment, there was evidence of widespread increases in 1CCPU not only in the non-occluded hemisphere (12 of the 15 areas studied) but also in the occluded hemisphere (13 of the 15 areas studied), while MK-801 posttreatment did not significantly increase 1CGU both in the normal and occluded hemispheres. These data indicate that MK-801 has a neuroprotective effect in focal cerebral ischemia and demonstrate that MK-801 provides widespread alterations of glucose utilization in conscious animals.

  19. Fatty Acid Methyl Esters and Solutol HS 15 Confer Neuroprotection After Focal and Global Cerebral Ischemia

    OpenAIRE

    Lin, Hung Wen; Saul, Isabel; Gresia, Victoria L.; Neumann, Jake T.; Dave, Kunjan R.; Perez-Pinzon, Miguel A.

    2013-01-01

    We previously showed that palmitic methyl ester (PAME) and stearic acid methyl ester (SAME) are simultaneously released from the sympathetic ganglion and PAME possesses potent vasodilatory properties which may be important in cerebral ischemia. Since PAME is a potent vasodilator simultaneously released with SAME, our hypothesis was that PAME/SAME confers neuroprotection in rat models of focal/global cerebral ischemia. We also examined the neuroprotective properties of Soluto...

  20. Facilitated beam-walking recovery during acute phase by kynurenic acid treatment in a rat model of photochemically induced thrombosis causing focal cerebral ischemia.

    Science.gov (United States)

    Abo, Masahiro; Yamauchi, Hideki; Suzuki, Masahiko; Sakuma, Mio; Urashima, Mitsuyoshi

    We previously demonstrated the presence of activated areas in the non-injured contralateral sensorimotor cortex in addition to the ipsilateral sensorimotor cortex of the area surrounding a brain infarction, using a rat model of focal photochemically induced thrombosis (PIT) and functional magnetic resonance imaging. Using this model, we next applied gene expression profiling to screen key molecules upregulated in the activated area. RNA was extracted from the ipsilateral and contralateral sensorimotor cortex to the focal brain infarction and from the sham controlled cortex, and hybridized to gene-expression profiling arrays containing 1,322 neurology-related genes. Results showed that glycine receptors were upregulated in both the ipsilateral and contralateral cortex to the focal ischemic lesion. To prove the preclinical significance of upregulated glycine receptors, kynurenic acid, an endogenous antagonist to glycine receptors on neuronal cells, was administered intrathecally. As a result, the kynurenic acid significantly improved behavioral recovery within 10 days from paralysis induced by the focal PIT (p beam walking. These results suggest that intrathecal administration of a glycine receptor antagonist may facilitate behavioral recovery during the acute phase after brain infarction. Copyright (c) 2006 S. Karger AG, Basel.

  1. Relaxation along a fictitious field (RAFF and Z-spectroscopy using alternating-phase irradiation (ZAPI in permanent focal cerebral ischemia in rat.

    Directory of Open Access Journals (Sweden)

    Kimmo T Jokivarsi

    Full Text Available Cerebral ischemia alters the molecular dynamics and content of water in brain tissue, which is reflected in NMR relaxation, diffusion and magnetization transfer (MT parameters. In this study, the behavior of two new MRI contrasts, Relaxation Along a Fictitious Field (RAFF and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI, were quantified together with conventional relaxation parameters (T1, T2 and T1ρ and MT ratios in acute cerebral ischemia in rat. The right middle cerebral artery was permanently occluded and quantitative MRI data was acquired sequentially for the above parameters for up to 6 hours. The following conclusions were drawn: 1 Time-dependent changes in RAFF and T1ρ relaxation are not coupled to those in MT. 2 RAFF relaxation evolves more like transverse, rather than longitudinal relaxation. 3 MT measured with ZAPI is less sensitive to ischemia than conventional MT. 4 ZAPI data suggest alterations in the T2 distribution of macromolecules in acute cerebral ischemia. It was shown that both RAFF and ZAPI provide complementary MRI information from acute ischemic brain tissue. The presented multiparametric MRI data may aid in the assessment of brain tissue status early in ischemic stroke.

  2. Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis.

    Science.gov (United States)

    Jeong, Ji Heun; Yu, Kwang Sik; Bak, Dong Ho; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Kim, Dong Kwan; Kim, Jwa-Jin; Han, Seung-Yun

    2016-11-01

    Previous studies have demonstrated that autophagy induced by caloric restriction (CR) is neuroprotective against cerebral ischemia. However, it has not been determined whether intermittent fasting (IF), a variation of CR, can exert autophagy-related neuroprotection against cerebral ischemia. Therefore, the neuroprotective effect of IF was evaluated over the course of two weeks in a rat model of focal cerebral ischemia, which was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). Specifically, the role of autophagy modulation as a potential underlying mechanism for this phenomenon was investigated. It was demonstrated that IF reduced infarct volume and brain edema, improved neurobehavioral deficits, and rescued neuronal loss after MCAO/R. Furthermore, neuronal apoptosis was decreased by IF in the rat cortex. An increase in the number of autophagosomes (APs) was demonstrated in the cortices of IF-treated rats, using immunofluorescence staining and transmission electron microscopy. Using immunoblots, an IF-induced increase was detected in microtubule-associated protein 1 light chain 3 (LC3)-II, Rab7, and cathepsin D protein levels, which corroborated previous morphological studies. Notably, IF reduced the accumulation of APs and p62, demonstrating that IF attenuated the MCAO/R-induced disturbance of autophagic flux in neurons. The findings of the present study suggest that IF-induced neuroprotection in focal cerebral ischemia is due, at least in part, to the minimization of autophagic flux disturbance and inhibition of apoptosis.

  3. Preliminary evaluation of [1-11C]octanoate as a PET tracer for studying cerebral ischemia. A PET study in rat and canine models of focal cerebral ischemia

    International Nuclear Information System (INIS)

    Kuge, Yuji; Kawashima, Hidefumi; Hashimoto, Tadatoshi

    2000-01-01

    Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the tricarboxylic acid (TCA) cycle after β-oxidation. We speculate that [1- 11 C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of [1- 11 C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of [ 15 O]H 2 O measured 1-2 h and 5-6 h after insult was compared with that of [1- 11 C]octanoate measured 3-4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with [ 15 O]H 2 O were lower than those determined with [1- 11 C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of [1- 11 C]octanoate was observed in the ischemic regions. The uptake of [1- 11 C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that [1- 11 C]octanoate provides functional information different from CBF. In conclusion, we found that [1- 11 C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia. (author)

  4. Regional cerebral blood flow in focal cortical epilepsy

    DEFF Research Database (Denmark)

    Hougaard, Kristina Dupont; Oikawa, T; Sveinsdottir, E

    1976-01-01

    Regional cerebral blood flow (rCBF) was studied in ten patients with focal cortical epilepsy. The blood flow was measured by the intra-arterial injection of xenon 133 (133Xe), and the isotope clearance was recorded by a multidetector scintillation camera with 254 detectors. Three patients were....... This finding accords with earlier studies. All nine patients studied in the interictal phase showed, either spontaneously or during activation by intermittent light, focal flow increases in areas presumed to comprise the epileptic focus. These interictal hyperemic foci probably reflect subictal neuronal...

  5. Total flavonoid of Litsea coreana leve exerts anti-oxidative effects and alleviates focal cerebral ischemia/reperfusion injury

    OpenAIRE

    Dong, Shuying; Tong, Xuhui; Li, Jun; Huang, Cheng; Hu, Chengmu; Jiao, Hao; Gu, Yuchen

    2013-01-01

    In this study, we hypothesized that total flavonoid of Litsea coreana leve (TFLC) protects against focal cerebral ischemia/reperfusion injury. TFLC (25, 50, 100 mg/kg) was administered orally to a rat model of focal ischemia/reperfusion injury, while the free radical scavenging agent, edaravone, was used as a positive control drug. Results of neurological deficit scoring, 2,3,5-triphenyl tetrazolium chloride staining, hematoxylin-eosin staining and biochemical tests showed that TFLC at differ...

  6. Neuronal network disturbance after focal ischemia in rats

    International Nuclear Information System (INIS)

    Kataoka, K.; Hayakawa, T.; Yamada, K.; Mushiroi, T.; Kuroda, R.; Mogami, H.

    1989-01-01

    We studied functional disturbances following left middle cerebral artery occlusion in rats. Neuronal function was evaluated by [14C]2-deoxyglucose autoradiography 1 day after occlusion. We analyzed the mechanisms of change in glucose utilization outside the infarct using Fink-Heimer silver impregnation, axonal transport of wheat germ agglutinin-conjugated-horseradish peroxidase, and succinate dehydrogenase histochemistry. One day after occlusion, glucose utilization was remarkably reduced in the areas surrounding the infarct. There were many silver grains indicating degeneration of the synaptic terminals in the cortical areas surrounding the infarct and the ipsilateral cingulate cortex. Moreover, in the left thalamus where the left middle cerebral artery supplied no blood, glucose utilization significantly decreased compared with sham-operated rats. In the left thalamus, massive silver staining of degenerated synaptic terminals and decreases in succinate dehydrogenase activity were observed 4 and 5 days after occlusion. The absence of succinate dehydrogenase staining may reflect early changes in retrograde degeneration of thalamic neurons after ischemic injury of the thalamocortical pathway. Terminal degeneration even affected areas remote from the infarct: there were silver grains in the contralateral hemisphere transcallosally connected to the infarct and in the ipsilateral substantia nigra. Axonal transport study showed disruption of the corticospinal tract by subcortical ischemia; the transcallosal pathways in the cortex surrounding the infarct were preserved. The relation between neural function and the neuronal network in the area surrounding the focal cerebral infarct is discussed with regard to ischemic penumbra and diaschisis

  7. Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats

    OpenAIRE

    Glendenning, Michele L.; Lovekamp-Swan, Tara; Schreihofer, Derek A.

    2008-01-01

    Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague-Dawley rats were ovariectomized an...

  8. MRI of experimental focal cerebral ischemia in sheep

    International Nuclear Information System (INIS)

    Foerschler, A.; Waldmin, D.; Gille, U.; Leipzig Univ.; Zimmer, C.

    2007-01-01

    Purpose: With respect to the specific characteristic of rete mirabile epidurale rostrale in sheep, the aim of this study was to investigate the use of time of flight (TOF) magnetic resonance angiography (MRA) to observe vascular anatomy and to validate MCA occlusion in a new model of experimental focal cerebral ischemia by permanent middle cerebral artery (MCA) occlusion in sheep (designed to study stroke therapy using autologous stem cells from umbilical cord blood). Furthermore, we wanted to assess the extent and natural time course of ischemic focal brain injury in sheep using functional and morphological magnetic resonance imaging (MRI). Materials and Method: 13 Merino sheep were examined. In 4 of the animals all, in 5 sheep 1 or 2 MCA branches were occluded and in 1 one case touched (sham operation). 4 controls did not undergo a surgical procedure. 23 MRI sessions were performed in 10 sheep. These sessions included T1, T2, T2 * sequences, diffusion-weighted imaging (DWI) and TOF MRA before and 2 - 46 days after the onset of stroke using a 1.5T clinical MR scanner. Corrosion casts of the cerebral arteries of 3 sheep were prepared and compared to MRA. Results: The MRA visualized the vessel anatomy or occlusion distal to the rete mirabile. Anatomical variants concerning the variant origin of the MCA and inconstant arteria choroidea rostralis and communicans rostralis were revealed. Sheep with occluded left MCA showed space occupying lesions with a drop in ADC values. Depending on the number of preserved MCA branches (0; 1; 2), highly significant (p < 0.001) differences in lesion size (21 ± 5.7; 13; 1.7 ± 1.3 ml) could be found. No indication of ischemia but minimal contusion damage was observed in the sham operated animal. (orig.)

  9. Spreading depression and focal venous cerebral ischemia enhance cortical neurogenesis

    Directory of Open Access Journals (Sweden)

    Ryo Tamaki

    2017-01-01

    Full Text Available Endogenous neurogenesis can arise from a variety of physiological stimuli including exercise, learning, or “enriched environment” as well as pathological conditions such as ischemia, epilepsy or cortical spreading depression. Whether all these conditions use a common trigger to set off endogenous neurogenesis is yet unclear. We hypothesized that cortical spreading depression (CSD induces neurogenesis in the cerebral cortex and dentate gyrus after cerebral venous ischemia. Forty-two Wistar rats alternatively underwent sham operation (Sham, induction of ten CSDs or venous ischemia provoked via occlusion of two adjacent superficial cortical vein followed by ten induced CSDs (CSD + 2-VO. As an additional control, 15 naïve rats received no intervention except 5-bromo-2′-deoxyuridine (BrdU treatment for 7 days. Sagittal brain slices (40 μm thick were co-stained for BrdU and doublecortin (DCX; new immature neuronal cells on day 9 or NeuN (new mature neuronal cells on day 28. On day 9 after sham operation, cell proliferation and neurogenesis occurred in the cortex in rats. The sole induction of CSD had no effect. But on days 9 and 28, more proliferating cells and newly formed neurons in the ipsilateral cortex were observed in rats subjected to CSD + 2VO than in rats subjected to sham operation. On days 9 and 28, cell proliferation and neurogenesis in the ipsilateral dentate gyrus was increased in sham-operated rats than in naïve rats. Our data supports the hypothesis that induced cortical neurogenesis after CSD + 2-VO is a direct effect of ischemia, rather than of CSD alone.

  10. [Estimation of Time-Dependent microRNA Expression Patterns in Brain Tissue, Leukocytes, and Blood Plasma of Rats under Photochemically Induced Focal Cerebral Ischemia].

    Science.gov (United States)

    Gusar, V A; Timofeeva, A V; Zhanin, I S; Shram, S I; Pinelis, V G

    2017-01-01

    miRNA expression over different time periods (24 and 48 h) using the quantitative RT-PCR and deep sequencing has been evaluated in a model of photochemically induced thrombosis. A combination of two approaches allowed us to determine the miRNA expression patterns caused by ischemia. Nine miRNAs, including let-7f-5p, miR-221-3p, miR-21-5p, miR-30c-5p, miR-30a-3p, miR-223-3p, miR-23a-3p, miR-22-5p, and miR-99a-5p, were differentially expressed in brain tissue and leukocytes of rats 48 h after onset of ischemia. In addition, six miRNAs were differentially expressed in the brain tissue and blood plasma of rats 24 h after exposure, among which miR-145-3p and miR-375-3p were downregulated and miR-19a-3p, miR-92a-3p, miR-188-5p, and miR-532-5p were upregulated. In our opinion, miR-188-5p and miR-532-5p may be considered to be new potential markers of ischemic injury. The level of miRNA expression tended to increase 48 h after the onset of ischemia in brain tissue and leukocytes, which reflects not only the local response in brain tissue due to inflammation, vascular endothelial dysfunction, and disorders of the permeability of the blood-brain barrier, but also the systemic response of the organism to multifactor molecular processes induced by ischemic injury.

  11. Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia.

    Science.gov (United States)

    Lin, Hung Wen; Saul, Isabel; Gresia, Victoria L; Neumann, Jake T; Dave, Kunjan R; Perez-Pinzon, Miguel A

    2014-02-01

    We previously showed that palmitic acid methyl ester (PAME) and stearic acid methyl ester (SAME) are simultaneously released from the sympathetic ganglion and PAME possesses potent vasodilatory properties which may be important in cerebral ischemia. Since PAME is a potent vasodilator simultaneously released with SAME, our hypothesis was that PAME/SAME confers neuroprotection in rat models of focal/global cerebral ischemia. We also examined the neuroprotective properties of Solutol HS15, a clinically approved excipient because it possesses similar fatty acid compositions as PAME/SAME. Asphyxial cardiac arrest (ACA, 6 min) was performed 30 min after PAME/SAME treatment (0.02 mg/kg, IV). Solutol HS15 (2 ml/kg, IP) was injected chronically for 14 days (once daily). Histopathology of hippocampal CA1 neurons was assessed 7 days after ACA. For focal ischemia experiments, PAME, SAME, or Solutol HS15 was administered following reperfusion after 2 h of middle cerebral artery occlusion (MCAO). 2,3,5-Triphenyltetrazolium staining of the brain was performed 24 h after MCAO and the infarct volume was quantified. Following ACA, the number of surviving hippocampal neurons was enhanced by PAME-treated (68%), SAME-treated (69%), and Solutol-treated HS15 (68%) rats as compared to ACA only-treated groups. Infarct volume was decreased by PAME (83%), SAME (68%), and Solutol HS15 (78%) as compared to saline (vehicle) in MCAO-treated animals. PAME, SAME, and Solutol HS15 provide robust neuroprotection in both paradigms of ischemia. This may prove therapeutically beneficial since Solutol HS15 is already administered as a solublizing agent to patients. With proper timing and dosage, administration of Solutol HS15 and PAME/SAME can be an effective therapy against cerebral ischemia.

  12. Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography.

    Science.gov (United States)

    Stöber, Franziska; Baldauf, Kathrin; Ziabreva, Iryna; Harhausen, Denise; Zille, Marietta; Neubert, Jenni; Reymann, Klaus G; Scheich, Henning; Dirnagl, Ulrich; Schröder, Ulrich H; Wunder, Andreas; Goldschmidt, Jürgen

    2014-01-01

    Neuronal damage shortly after onset or after brief episodes of cerebral ischemia has remained difficult to assess with clinical and preclinical imaging techniques as well as with microscopical methods. We here show, in rodent models of middle cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral ischemia can be mapped with single-cell resolution using thallium autometallography (TlAMG), a histochemical technique for the detection of the K(+)-probe thallium (Tl(+)) in the brain. We intravenously injected rats and mice with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that releases Tl(+) after crossing the blood-brain barrier. We found, within the territories of the affected arteries, areas of markedly reduced neuronal Tl(+) uptake in all animals at all time points studied ranging from 15 minutes to 24 hours after MCAO. In large lesions at early time points, areas with neuronal and astrocytic Tl(+) uptake below thresholds of detection were surrounded by putative penumbral zones with preserved but diminished Tl(+) uptake. At 24 hours, the areas of reduced Tl(+)uptake matched with areas delineated by established markers of neuronal damage. The results suggest the use of (201)TlDDC for preclinical and clinical single-photon emission computed tomography (SPECT) imaging of hyperacute alterations in brain K(+) metabolism and prediction of tissue viability in cerebral ischemia.

  13. Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse.

    Science.gov (United States)

    Xu, Kui; Ye, Lena; Sharma, Katyayini; Jin, Yongming; Harrison, Matthew M; Caldwell, Tylor; Berthiaume, Jessica M; Luo, Yu; LaManna, Joseph C; Puchowicz, Michelle A

    2017-01-01

    Over the past decade we have consistently shown that ketosis is neuroprotective against ischemic insults in rats. We reported that diet-induced ketotic rats had a significant reduction in infarct volume when subjected to middle cerebral artery occlusion (MCAO), and improved survival and recovery after cardiac arrest and resuscitation. The neuroprotective mechanisms of ketosis (via ketogenic diet; KG) include (i) ketones are alternate energy substrates that can restore energy balance when glucose metabolism is deficient and (ii) ketones modulate cell-signalling pathways that are cytoprotective. We investigated the effects of diet-induced ketosis following transient focal cerebral ischemia in mice. The correlation between levels of ketosis and hypoxic inducible factor-1alpha (HIF-1α), AKT (also known as protein kinase B or PKB) and 5' AMP-activated protein kinase (AMPK) were determined. Mice were fed with KG diet or standard lab-chow (STD) diet for 4 weeks. For the MCAO group, mice underwent 60 min of MCAO and total brain infarct volumes were evaluated 48 h after reperfusion. In a separate group of mice, brain tissue metabolites, levels of HIF-1α, phosphorylated AKT (pAKT), and AMPK were measured. After feeding a KG diet, levels of blood ketone bodies (beta-hydroxyburyrate, BHB) were increased. There was a proportional decrease in infarct volumes with increased blood BHB levels (KG vs STD; 4.2 ± 0.6 vs 7.8 ± 2.2 mm 3 , mean ± SEM). A positive correlation was also observed with HIF-1α and pAKT relative to blood BHB levels. Our results showed that chronic ketosis can be induced in mice by KG diet and was neuroprotective against focal cerebral ischemia in a concentration dependent manner. Potential mechanisms include upregulation of cytoprotective pathways such as those associated with HIF-1α, pAKT and AMPK.

  14. Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Thigarajah, Rushani; Edvinsson, Lars

    2014-01-01

    BACKGROUND AND PURPOSE: Increased expression of endothelin receptor type B (ETBR), a vasoactive receptor, has recently been implied in the reduced cerebral blood flow and exacerbated neuronal damage after ischemia-reperfusion (I/R). The study explores the regulatory mechanisms of ETBR to identify...... drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy. METHODS: We have employed in vitro methods on human and rat cerebral arteries to study the regulatory mechanisms and the efficacy of target selective inhibitor, Mithramycin A (Mit...... the ETBR mRNA and protein levels. It also significantly reduced the ETBR mediated cerebrovascular contractility. Detailed analysis indicated that ERK1/2 mediated phosphorylation of Sp1 might be essential for ETBR transcription. CONCLUSION: Transcription factor Sp1 regulates the ETBR mediated...

  15. Reduced Mechanical Stretch Induces Enhanced Endothelin B Receptor-mediated Contractility via Activation of Focal Adhesion Kinase and Extra Cellular-regulated Kinase 1/2 in Cerebral Arteries from Rat

    DEFF Research Database (Denmark)

    Spray, Stine; Rasmussen, Marianne N P; Skovsted, Gry F

    2016-01-01

    that rapid and sustained reduction in wall tension/stretch is a possible trigger mechanism for this vascular remodelling. Isolated rat middle cerebral artery (MCA) segments were incubated in a wire-myograph with or without mechanical stretch, prior to assessment of their contractile response to the selective...... expression to SMC expression and 2) an increased calcium sensitivity of the SMCs due to an increased expression of the calcium channel transient receptor potential canonical 1. Collectively, our results present a possible mechanism linking lack of vessel wall stretch/tension to changes in ETB receptor...

  16. Opposite effects of the gap junction blocker octanol on focal cerebral ischemia occluded for different durations.

    Science.gov (United States)

    Ding, Wenting; Zhou, Lequan; Liu, Wei; Guan, Li; Li, Xiaoying; Liu, Haimei; Yan, Fuman; Xu, Jinwen; Zeng, Weiyong; Qiu, Min

    2014-06-01

    Protectants and executioners have been demonstrated to be used by gap junctions in focal cerebral ischemia. Certain researchers hypothesized that the opposite role of gap junctions may be associated with the injury extent, which has been demonstrated to be highly correlated with occlusion duration. In order to examine this hypothesis directly, the effects of octanol, a frequently used drug, were examined to investigate the role of gap junctions, in rats following middle cerebral artery occlusion (MCAO) for 30 min/2 h and 24 h reperfusion, respectively. Octanol significantly reduced the infarct volume following 2 h of occlusion concomitant with lower neurological deficits, whereas it enlarged the infarct volume following 30 min of occlusion. Consistently, octanol attenuated the number of transferase dUTP nick-end labeling (TUNEL) positive neurons in the hippocampal CA1 region following 2 h of occlusion, while opposite effects were observed for 30 min of occlusion. Further immunohistochemical studies demonstrated that the expression of B-cell leukemia-2 (Bcl-2, anti-apoptotic protein) was upregulated and that Bcl-2-associated X (Bax, proapoptotic protein) was downregulated following 2 h of occlusion in the octanol group compared with the ischemic group. Conversely, octanol downregulated the expression of the Bcl-2 protein concomitant with increased Bax protein following 30 min of occlusion. These results indicated that the gap junction blocker octanol can protect against ischemic injury following long-term occlusion, however, can aggravate ischemic injury following short-term occlusion.

  17. Ebselen reduces autophagic activation and cell death in the ipsilateral thalamus following focal cerebral infarction.

    Science.gov (United States)

    Li, Yiliang; Zhang, Jian; Chen, Li; Xing, Shihui; Li, Jingjing; Zhang, Yusheng; Li, Chuo; Pei, Zhong; Zeng, Jinsheng

    2015-07-23

    Previous studies have demonstrated that both oxidative stress and autophagy play important roles in secondary neuronal degeneration in the ipsilateral thalamus after distal middle cerebral artery occlusion (MCAO). This study aimed to investigate whether oxidative stress is associated with autophagy activation within the ipsilateral thalamus after distal MCAO. Sixty stroke-prone renovascular hypertensive rats were subjected to distal MCAO or sham operation, and were killed at 14 days after MCAO. Mn-SOD, LC3-II, Beclin-1 and p62 expression were evaluated by immunostaining and immunoblotting. Secondary damage in the thalamus was assessed with Nissl staining and immunostaining. The association of oxidative stress with autophagy activation was investigated by the antioxidant, ebselen. We found that treatment with ebselen at 24h after MCAO significantly reduced the expression of Mn-SOD in the ipsilateral thalamus at 14 days following focal cerebral infarction. In parallel, it prevented the elevation of LC3-II and Beclin-1, and the reduction of p62. Furthermore, ebselen attenuated the neuronal loss and gliosis in the ipsilateral thalamus. These results suggested that ebselen reduced oxidative stress, autophagy activation and secondary damage in the ipsilateral thalamus following MCAO. There are associations between oxidative stress, autophagy activation and secondary damage in the thalamus after MCAO. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Breviscapine confers a neuroprotective efficacy against transient focal cerebral ischemia by attenuating neuronal and astrocytic autophagy in the penumbra.

    Science.gov (United States)

    Pengyue, Zhang; Tao, Guo; Hongyun, He; Liqiang, Yang; Yihao, Deng

    2017-06-01

    Breviscapine is a flavonoid derived from a traditional Chinese herb Erigerin breviscapus (Vant.) Hand-Mazz, and has been extensively used in clinical treatment for cerebral stroke in China, but the underlying pharmacological mechanisms are still unclear. In present study, we investigated whether breviscapine could confer a neuroprotection against cerebral ischemia injury by targeting autophagy mechanisms. A cerebral stroke model in Sprague-Dawley rats was prepared by middle cerebral artery occlusion (MCAO), rats were then randomly divided into 5 groups: MCAO+Bre group, rats were treated with breviscapine; MCAO+Tat-Beclin-1 group, animals were administrated with specific autophagy inducer Tat-Beclin-1; MCAO+Bre+Tat-Beclin-1 group, rats were treated with both breviscapine and Tat-Beclin-1, MCAO+saline group, rats received the same volume of physiological saline, and Sham surgery group. The autophagy levels in infarct penumbra were evaluated by western blotting, real-time PCR and immunofluorescence 7days after the insult. Meanwhile, infarct volume, brain water content and neurological deficit score were assessed. The results illustrated that the infarct volume, brain water content and neurofunctional deficiency were significantly reduced by 7days of breviscapine treatment in MCAO+Bre group, compared with those in MCAO+saline group. Meanwhile, the western blotting, quantitative PCR and immunofluorescence showed that the autophagy in both neurons and astrocytes at the penumbra were markedly attenuated by breviscapine admininstration. Moreover, these pharmacological effects of breviscapine could be counteracted by autophagy inducer Tat-Beclin-1. Our study suggests that breviscapine can provide a neuroprotection against transient focal cerebral ischemia, and this biological function is associated with attenuating autophagy in both neurons and astrocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Therapeutic potential of the novel hybrid molecule JM-20 against focal cortical ischemia in rats

    Directory of Open Access Journals (Sweden)

    Yanier Núñez Figueredo

    2016-08-01

    Full Text Available Context: Despite the great mortality and morbidity of stroke, treatment options remain limited. We previously showed that JM-20, a novel synthetic molecule, possessed a strong neuroprotective effect in rats subjected to transient middle cerebral artery occlusion. However, to verify the robustness of the pre-clinical neuroprotective effects of JM-20 to get good prognosis in the translation to the clinic, it is necessary to use other experimental models of brain ischemia. Aims: To evaluate the neuroprotective effects of JM-20 following the onset of permanent focal cerebral ischemia induced in rats by thermocoagulation of blood into pial blood vessels of cerebral cortices. Methods: Ischemic lesion was induced by thermocoagulation of blood into pial blood vessels of primary motor and somatosensory cortices. Behavioral performance was evaluated by the cylinder testing for a period of 2, 3 and 7 days after surgery, and was followed by histopathological study in brain cortex stained with hematoxylin- eosin. Results: Ischemic injury resulted in impaired function of the forelimb evidenced by high asymmetry punctuation, and caused histopathological alterations indicative of tissue damage at cerebral cortex. JM-20 treatment (4 and 8 mg/kg significantly decreased asymmetry scores and histological alterations with a marked preservation of cortical neurons. Conclusions: The effects of permanent brain ischemia were strongly attenuated by JM-20 administration, which expands and improves the current preclinical data of JM-20 as neuroprotector against cerebral ischemia, and strongly support the examination of its translation to the clinic to treat acute ischemic stroke.

  20. Mass spectrometry imaging of biomarker lipids for phagocytosis and signalling during focal cerebral ischaemia

    DEFF Research Database (Denmark)

    Nielsen, Mette M B; Lambertsen, Kate L; Clausen, Bettina H

    2016-01-01

    biomarker CD11b, and probably with cholesteryl ester. Mass spectrometry imaging can visualize spatiotemporal changes in the lipidome during the progression and resolution of focal cerebral inflammation and suggests that BMP(22:6/22:6) and N-acyl-phosphatidylethanolamines can be used as biomarkers......Focal cerebral ischaemia has an initial phase of inflammation and tissue injury followed by a later phase of resolution and repair. Mass spectrometry imaging (desorption electrospray ionization and matrix assisted laser desorption ionization) was applied on brain sections from mice 2 h, 24 h, 5d, 7...

  1. Aquaporin-4 inhibition mediates piroxicam-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rodents.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana; Yavagal, Dileep R

    2013-01-01

    Aquaporin-4(AQP4) is an abundant water channel protein in brain that regulates water transport to maintain homeostasis. Cerebral edema resulting from AQP4 over expression is considered to be one of the major determinants for progressive neuronal insult during cerebral ischemia. Although, both upregulation and downregulation of AQP4 expression is associated with brain pathology, over expression of AQP4 is one of the chief contributors of water imbalance in brain during ischemic pathology. We have found that Piroxicam binds to AQP4 with optimal binding energy value. Thus, we hypothesized that Piroxicam is neuroprotective in the rodent cerebral ischemic model by mitigating cerebral edema via AQP4 regulation. Rats were treated with Piroxicam OR placebo at 30 min prior, 2 h post and 4 h post 60 minutes of MCAO followed by 24 hour reperfusion. Rats were evaluated for neurological deficits and motor function just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, biochemical analysis, RT-PCR and western blot experiments. Piroxicam pretreatment thirty minutes prior to ischemia and four hour post reperfusion afforded neuroprotection as evident through significant reduction in cerebral infarct volume, improvement in motor behavior, neurological deficit and reduction in brain edema. Furthermore, ischemia induced surge in levels of nitrite and malondialdehyde were also found to be significantly reduced in ischemic brain regions in treated animals. This neuroprotection was found to be associated with inhibition of acid mediated rise in intracellular calcium levels and also downregulated AQP4 expression. Findings of the present study provide significant evidence that Piroxicam acts as a potent AQP4 regulator and renders neuroprotection in focal cerebral ischemia. Piroxicam could be clinically exploited for the treatment of brain stroke along with other anti-stroke therapeutics in future.

  2. Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.

    Science.gov (United States)

    Liu, Xiaobai; Wang, Zhenhua; Wang, Ping; Yu, Bo; Liu, Yunhui; Xue, Yixue

    2013-07-21

    It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

  3. White matter integrity and cerebral network topology in focal epilepsy

    NARCIS (Netherlands)

    Otte, W.M.

    2012-01-01

    Worldwide more than fifty million people suffer from recurrent spontaneous seizures. Seizures are considered to be harmful to the brain and may have adverse long-term behavioral and cognitive consequences in particular in people with focal epilepsies that do not respond to pharmacotherapy.

  4. Cerebroprotective Effect of Moringa oleifera against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2013-01-01

    Full Text Available The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg−1 was orally given to male Wistar rats (300–350 g once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

  5. Cerebral microbleeds in a neonatal rat model.

    Directory of Open Access Journals (Sweden)

    Brianna Carusillo Theriault

    Full Text Available In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter.Pregnant Wistar rats were subjected to intrauterine ischemia (IUI and low-dose maternal lipopolysaccharide (mLPS at embryonic day (E 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks.mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2 and protein (CD31, MMP2, MMP9 for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls.In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development.

  6. PPARγ agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

    International Nuclear Information System (INIS)

    Lee, Seong-Ryong; Kim, Hahn-Young; Hong, Jung-Suk; Baek, Won-Ki; Park, Jong-Wook

    2009-01-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation with pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.

  7. Alleviation of glutamate mediated neuronal insult by piroxicam in rodent model of focal cerebral ischemia: a possible mechanism of GABA agonism.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

    2014-12-01

    Neurotransmitter imbalance is an inevitable outcome in cerebral ischemia that leads to neuronal death. In the present study, we evaluated the effects of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID), on extracellular brain glutamate and γ-aminobutyric acid (GABA) release, survival time, and neuronal cell death. Transient focal cerebral ischemia in male Charles Foster rat led to neuronal infarction and compromised intrinsic antioxidant status. Thirty-minute preadministration of piroxicam (10 mg/kg b.w.) showed a significant (P piroxicam administration in stroke rat significantly reduced (P piroxicam attenuates extracellular glutamate release and also reduces neuronal cell death due to reduction in oxidative stress in cerebral ischemia. Our results also indicate a consequent increase of extracellular GABA in brain regions administered with piroxicam, which hints that piroxicam alleviates glutamate excitotoxicity possibly by GABA agonism.

  8. Diffusion-weighted magnetic resonance imaging reflects activation of signal transducer and activator of transcription 3 during focal cerebral ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Wen-juan Wu

    2017-01-01

    Full Text Available Signal transducer and activator of transcription (STAT is a unique protein family that binds to DNA, coupled with tyrosine phosphorylation signaling pathways, acting as a transcriptional regulator to mediate a variety of biological effects. Cerebral ischemia and reperfusion can activate STATs signaling pathway, but no studies have confirmed whether STAT activation can be verified by diffusion-weighted magnetic resonance imaging (DWI in rats after cerebral ischemia/reperfusion. Here, we established a rat model of focal cerebral ischemia injury using the modified Longa method. DWI revealed hyperintensity in parts of the left hemisphere before reperfusion and a low apparent diffusion coefficient. STAT3 protein expression showed no significant change after reperfusion, but phosphorylated STAT3 expression began to increase after 30 minutes of reperfusion and peaked at 24 hours. Pearson correlation analysis showed that STAT3 activation was correlated positively with the relative apparent diffusion coefficient and negatively with the DWI abnormal signal area. These results indicate that DWI is a reliable representation of the infarct area and reflects STAT phosphorylation in rat brain following focal cerebral ischemia/reperfusion.

  9. Effect of baicalin on the autophagy and Beclin-1 expression in rats with cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Xiang-Long Hong

    2016-07-01

    Full Text Available Objective: To explore the effect of baicalin on the autophagy and Beclin-1 expression in rats with cerebral ischemia, and the role of autophagy in the cerebral ischemia injury. Methods: The healthy male SD rats were randomized into the sham operation group, the ischemia model group, baicalin treatment group (100 mg/kg, and 3MA group (15 mg/kg, with 10 rats in each group. Transient focal cerebral ischemia injury model in rats was induced by occlusion of middle cerebral artery (MCA for 180 min. The rats were given the corresponding drugs through the tail veins 30 min before molding. Half of the specimens were used for TTC staining to analyze the cerebral infarction volume. The others were used to determine the expression of Beclin-1 in the brain tissues by Western-blot. Results: When compared with the ischemia model group, the cerebral infarction volume in 3MA group was significantly increased, while that in baicalin treatment group was significantly reduced, and the comparison among the groups was statistically significant. When compared with the ischemia model group, Beclin-1 expression level in baicalin treatment group was significantly elevated, while Beclin-1 expression level in 3MA group was significantly higher than that in the sham-operation group but lower than that in the ischemia model group. Conclusions: The autophagy level of brain tissues in normal rats is low. The cerebral ischemia can activate autophagy. The activated autophagy is probably involved in the neuroprotection of cerebral ischemia injury. Application of 3MA to inhibit the occurrence of autophagy can aggravate the cerebral injury. Baicalin can significantly improve the cerebral ischemia injury and promote the occurrence of autophagy, whose mechanism is probably associated with the up-regulation of Beclin-1 expression to promote the activation of type III PI3K signal transduction pathway.

  10. Opiates and cerebral functional activity in rats

    International Nuclear Information System (INIS)

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid [1- 14 C] octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions

  11. Opiates and cerebral functional activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.

  12. Rapamycin preconditioning attenuates transient focal cerebral ischemia/reperfusion injury in mice.

    Science.gov (United States)

    Yin, Lele; Ye, Shasha; Chen, Zhen; Zeng, Yaoying

    2012-12-01

    Rapamycin, an mTOR inhibitor and immunosuppressive agent in clinic, has protective effects on traumatic brain injury and neurodegenerative diseases. But, its effects on transient focal ischemia/reperfusion disease are not very clear. In this study, we examined the effects of rapamycin preconditioning on mice treated with middle cerebral artery occlusion/reperfusion operation (MCAO/R). We found that the rapamycin preconditioning by intrahippocampal injection 20 hr before MCAO/R significantly improved the survival rate and longevity of mice. It also decreased the neurological deficit score, infracted areas and brain edema. In addition, rapamycin preconditioning decreased the production of NF-κB, TNF-α, and Bax, but not Bcl-2, an antiapoptotic protein in the ischemic area. From these results, we may conclude that rapamycin preconditioning attenuate transient focal cerebral ischemia/reperfusion injury and inhibits apoptosis induced by MCAO/R in mice.

  13. Inflammation and the neurovascular unit in the setting of focal cerebral ischemia.

    Science.gov (United States)

    del Zoppo, G J

    2009-02-06

    Responses to focal cerebral ischemia by neurons and adjacent microvessels are rapid, simultaneous, and topographically related. Recent observations indicate the simultaneous appearance of proteases by components of nearby microvessels that are also expressed by neurons in the ischemic territory, implying that the events could be coordinated. The structural relationship of neurons to their microvascular supply, the direct functional participation of glial cells, and the observation of a highly ordered microvessel-neuron response to ischemia suggest that these elements are arranged in and behave in a unitary fashion, the neurovascular unit. Their roles as a unit in the stimulation of cellular inflammation and the generation of inflammatory mediators during focal cerebral ischemia have not been explored yet. However, components of the neurovascular unit both generate and respond to these influences under the conditions of ischemia. Here we briefly explore the potential inter-relationships of the components of the neurovascular unit with respect to their potential roles in ischemia-induced inflammatory responses.

  14. Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats.

    Science.gov (United States)

    Glendenning, Michele L; Lovekamp-Swan, Tara; Schreihofer, Derek A

    2008-11-14

    Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague-Dawley rats were ovariectomized and divided into placebo and estradiol-treated groups. Two weeks later, halothane-anesthetized rats underwent middle cerebral artery (MCA) occlusion by interparenchymal stereotactic injection of the potent vasoconstrictor endothelin 1 (180pmoles/2microl) near the middle cerebral artery. Laser-Doppler flowmetry (LDF) revealed similar reductions in cerebral blood flow in both groups. Animals were behaviorally evaluated before, and 2 days after, stroke induction, and infarct size was evaluated. In agreement with other models, estrogen treatment significantly reduced infarct size evaluated by both TTC and Fluoro-Jade staining and behavioral deficits associated with stroke. Stroke size was significantly correlated with LDF in both groups, suggesting that cranial perfusion measures can enhance success in this model.

  15. Functional MR imaging using sensory and motor task in brain tumors and other focal cerebral lesions

    International Nuclear Information System (INIS)

    Ok, Chul Su; Lim, Myung Kwan; Yu, Ki Bong; Kim, Hyung Jin; Suh, Chang Hae

    2002-01-01

    To determine the usefulness of the functional MRI (fMRI) using motor and sensory stimuli in patients with brain tumors of focal cerebral lesions. This study involved five patients with brain tumors (n=2) or cerebral lesions (cysticercosis (n=1), arteriovenous malformation (n=1), focal infarction (n=1) and seven normal controls. For MR examinations a 1.5T scanner was used, and during motor or sensory stimulation, the EPI BOLD technique was employed. For image postprocessing an SPM program was utilized. In volunteers, contralateral sensori-motor cortices were activated by both motor and sensory stimuli, while supplementary motor cortices were activated by motor stimuli and other sensory cortices by sensory stimuli. Preoperative evaluation of the relationship between lesions and important sensory and motor areas was possible, and subsequent surgery was thus successful, involving no severe complications. Activation of ipsilateral or other areas occurred in patients with destruction of a major sensory and/or motor area, suggesting compensatory reorganization. fMRI could be a useful supportive method for determining the best approach to surgery treatment in patients with brain tumors or focal cerebral lesions

  16. Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

    Directory of Open Access Journals (Sweden)

    Zhao Yu

    2012-09-01

    Full Text Available Abstract Background Electroacupuncture (EA pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. Results EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. Conclusions EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

  17. Dynamic change in cerebral microcirculation and focal cerebral metabolism in experimental subarachnoid hemorrhage in rabbits.

    Science.gov (United States)

    Song, Jin-Ning; Chen, Hu; Zhang, Ming; Zhao, Yong-Lin; Ma, Xu-Dong

    2013-03-01

    Regional cerebral blood flow (rCBF) in the cerebral metabolism and energy metabolism measurements can be used to assess blood flow of brain cells and to detect cell activity. Changes of rCBF in the cerebral microcirculation and energy metabolism were determined in an experimental model of subarachnoid hemorrhage (SAH) model in 56 large-eared Japanese rabbits about 12 to 16-month old. Laser Doppler flowmetry was used to detect the blood supply to brain cells. Internal carotid artery and vein blood samples were used for duplicate blood gas analysis to assess the energy metabolism of brain cells. Cerebral blood flow (CBF) was detected by single photon emission computed tomography (SPECT) perfusion imaging using Tc-99m ethyl cysteinate dimer (Tc-99m ECD) as an imaging reagent. The percentage of injected dose per gram of brain tissue was calculated and analyzed. There were positive correlations between the percentage of radionuclide injected per gram of brain tissue and rCBF supply and cerebral metabolic rate for oxygen (P brain cells after SAH, and also found that deterioration of energy metabolism of brain cells played a significant role in the development of SAH. There are matched reductions in CBF and metabolism. Thus, SPECT imaging could be used as a noninvasive method to detect CBF.

  18. Effect of Panax notoginseng saponins on the content of IL-8 in serum after cerebral ischemia-reperfusion in rat

    International Nuclear Information System (INIS)

    He Wei; Zhu Zunping

    2002-01-01

    Objective: To investigate the effect of Panax notoginseng saponins (Pns) against cerebral ischemia-reperfusion injury. Methods: Focal cerebral ischemia-reperal ischemia-reperfusion model in rat was established by occlusion the middle cerebral artery for 2 h, after 3 h reperfusion. The serum concentration of IL-8 was detected with radioimmunoassay (RIA). Results: Png 50 mg·kg -1 ip, qd x 7d before MCAO decreased the serum content of IL-8 after ischemia-reperfusion. Conclusion: Pns has protective effect against cerebral ischemia-reperfusion injury by decreased the serum content of IL-8

  19. Sequential assessment of regional cerebral blood flow, regional cerebral blood volume, and blood-brain barrier in focal cerebral ischemia: a case report

    International Nuclear Information System (INIS)

    Di Piero, V.; Perani, D.; Savi, A.; Gerundini, P.; Lenzi, G.L.; Fazio, F.

    1986-01-01

    Regional CBF (rCBF) and regional cerebral blood volume (rCBV) were evaluated by N,N,N'-trimethyl-N'-(2)-hydroxy-3-methyl-5-[123I]iodobenzyl-1, 3-propanediamine-2 HCl- and /sup 99m/TC-labeled red blood cells, respectively, and single-photon emission computerized tomography (SPECT) in a patient with focal cerebral ischemia. Sequential transmission computerized tomography (TCT) and SPECT functional data were compared with clinical findings to monitor the pathophysiological events occurring in stroke. A lack of correlation between rCBF-rCBV distributions and blood-brain barrier (BBB) breakdown was found in the acute phase. In the face of more prolonged alteration of BBB, as seen by TCT enhancement, a rapid evolution of transient phenomena such as luxury perfusion was shown by SPECT studies. Follow-up of the patient demonstrated a correlation between the neurological recovery and a parallel relative improvement of the cerebral perfusion

  20. Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

    Science.gov (United States)

    Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

    2014-01-01

    Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Cerebral ammonia metabolism in hyperammonemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, A J; Mora, S N; Cruz, N F; Gelbard, A S

    1985-06-01

    The short-term metabolic fate of blood-borne (/sup 13/N)ammonia was determined in the brains of chronically (8- or 14-week portacaval-shunted rats) or acutely (urease-treated) hyperammonemic rats. Using a freeze-blowing technique it was shown that the overwhelming route for metabolism of blood-borne (/sup 13/N)ammonia in normal, chronically hyperammonemic and acutely hyperammonemic rat brain was incorporation into glutamine (amide). However, the rate of turnover of (/sup 13/N)ammonia to L-(amide-/sup 13/N)glutamine was slower in the hyperammonemic rat brain than in the normal rat brain. The activities of several enzymes involved in cerebral ammonia and glutamate metabolism were also measured in the brains of 14-week portacaval-shunted rats. The rat brain appears to have little capacity to adapt to chronic hyperammonemia because there were no differences in activity compared with those of weight-matched controls for the following brain enzymes involved in glutamate/ammonia metabolism: glutamine synthetase, glutamate dehydrogenase, aspartate aminotransferase, glutamine transaminase, glutaminase, and glutamate decarboxylase. The present findings are discussed in the context of the known deleterious effects on the CNS of high ammonia levels in a variety of diseases.

  2. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    DEFF Research Database (Denmark)

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H

    2015-01-01

    of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation......BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number...

  3. Focal increase of blood flow in the cerebral cortex of man during vestibular stimulation

    DEFF Research Database (Denmark)

    Friberg, L; Olsen, T S; Roland, P E

    1985-01-01

    This study is an attempt to reveal projection areas for vestibular afferents to the human brain. Changes in regional cerebral blood flow (rCBF) were measured over 254 cortical regions during caloric vestibular stimulation with warm water (44 degrees C). rCBF was measured when the external auditory...... meatus was irrigated with water at body temperature as a control to vestibular stimulation. During vestibular stimulation there was only a single cortical area, located in the superior temporal region, which showed a consistent focal activation in the hemisphere contralateral to the stimulated side...... stimulation that gives rise to the associated conscious vestibular sensation of vertigo....

  4. Carvacrol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in Middle Cerebral Artery Occlusion Rats.

    Science.gov (United States)

    Li, Zhenlan; Hua, Cong; Pan, Xiaoqiang; Fu, Xijia; Wu, Wei

    2016-08-01

    Increasing evidence demonstrates that inflammation plays an important role in cerebral ischemia. Carvacrol, a monoterpenic phenol, is naturally occurring in various plants belonging to the family Lamiaceae and exerts protective effects in a mice model of focal cerebral ischemia/reperfusion injury by reducing infarct volume and decreasing the expression of cleaved caspase-3. However, the anti-inflammatory mechanisms by which carvacrol protect the brain have yet to be fully elucidated. We investigated the effects of carvacrol on inflammatory reaction and inflammatory mediators in middle cerebral artery occlusion rats. The results of the present study showed that carvacrol inhibited the levels of inflammatory cytokines and myeloperoxidase (MPO) activity, as well as the expression of iNOS and COX-2. It also increased SOD activity and decreased MDA level in ischemic cortical tissues. In addition, carvacrol treatment suppressed the ischemia/reperfusion-induced increase in the protein expression of nuclear NF-kB p65. In conclusion, we have shown that carvacrol inhibits the inflammatory response via inhibition of the NF-kB signaling pathway in a rat model of focal cerebral ischemia. Therefore, carvacrol may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

  5. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

    International Nuclear Information System (INIS)

    Fox, P.T.; Raichle, M.E.

    1986-01-01

    Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

  6. MRI of experimental focal cerebral ischemia in sheep; MR-Bildgebung eines experimentellen Schlaganfallmodells beim Schaf

    Energy Technology Data Exchange (ETDEWEB)

    Foerschler, A. [Universitaetsklinikum Leipzig (Germany). Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie, Abt. fuer Neuroradiologie; Boltze, J. [Universitaetsklinikum Leipzig (Germany). Inst. fuer Klinische Immunologie und Transfusionsmedizin; Fraunhofer-Inst. fuer Zelltherapie und Immunologie (Germany); Waldmin, D. [Leipzig Univ. (Germany). Veterinaer-Anatomisches Inst.; Gille, U. [Fraunhofer-Inst. fuer Zelltherapie und Immunologie (Germany); Leipzig Univ. (Germany). Veterinaer-Anatomisches Inst.; Zimmer, C. [Technische Univ. Muenchen (Germany). Klinikum rechts der Isar, Abt. fuer Neuroradiologie

    2007-05-15

    Purpose: With respect to the specific characteristic of rete mirabile epidurale rostrale in sheep, the aim of this study was to investigate the use of time of flight (TOF) magnetic resonance angiography (MRA) to observe vascular anatomy and to validate MCA occlusion in a new model of experimental focal cerebral ischemia by permanent middle cerebral artery (MCA) occlusion in sheep (designed to study stroke therapy using autologous stem cells from umbilical cord blood). Furthermore, we wanted to assess the extent and natural time course of ischemic focal brain injury in sheep using functional and morphological magnetic resonance imaging (MRI). Materials and Method: 13 Merino sheep were examined. In 4 of the animals all, in 5 sheep 1 or 2 MCA branches were occluded and in 1 one case touched (sham operation). 4 controls did not undergo a surgical procedure. 23 MRI sessions were performed in 10 sheep. These sessions included T1, T2, T2{sup *} sequences, diffusion-weighted imaging (DWI) and TOF MRA before and 2 - 46 days after the onset of stroke using a 1.5T clinical MR scanner. Corrosion casts of the cerebral arteries of 3 sheep were prepared and compared to MRA. Results: The MRA visualized the vessel anatomy or occlusion distal to the rete mirabile. Anatomical variants concerning the variant origin of the MCA and inconstant arteria choroidea rostralis and communicans rostralis were revealed. Sheep with occluded left MCA showed space occupying lesions with a drop in ADC values. Depending on the number of preserved MCA branches (0; 1; 2), highly significant (p < 0.001) differences in lesion size (21 {+-} 5.7; 13; 1.7 {+-} 1.3 ml) could be found. No indication of ischemia but minimal contusion damage was observed in the sham operated animal. (orig.)

  7. Downstream Toll-like receptor signaling mediates adaptor-specific cytokine expression following focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Bolanle Famakin

    2012-07-01

    Full Text Available Abstract Background Deletion of some Toll-like receptors (TLRs affords protection against cerebral ischemia, but disruption of their known major downstream adaptors does not. To determine whether compensation in the production of downstream effectors by one pathway when the other is disrupted can explain these findings, we examined cytokine/chemokine expression and inflammatory infiltrates in wild-type (WT, MyD88−/− and TRIF-mutant mice following permanent middle cerebral artery occlusion (pMCAO. Methods Cytokine/chemokine expression was measured with a 25-plex bead array in the serum and brains of all three groups of mice at baseline (no surgery/naïve and at 3 hours and 24 hours following pMCAO. Brain inflammatory and neutrophil infiltrates were examined 24 hours following pMCAO. Results IL-6, keratinocyte chemoattractant (KC, granulocyte colony-stimulating factor (G-CSF and IL-10 were significantly decreased in MyD88−/− mice compared to WT mice following pMCAO. Significantly, decreased levels of the neutrophil chemoattractants KC and G-CSF corresponded with a trend toward fewer neutrophils in the brains of MyD88−/− mice. IP-10 was significantly decreased when either pathway was disrupted. MIP-1α was significantly decreased in TRIF-mutant mice, consistent with TRIF-dependent production. MyD88−/− mice showed elevations of a number of Th2 cytokines, such as IL-13, at baseline, which became significantly decreased following pMCAO. Conclusions Both MyD88 and TRIF mediate pathway-specific cytokine production following focal cerebral ischemia. Our results also suggest a compensatory Th2-type skew at baseline in MyD88−/− mice and a paradoxical switch to a Th1 phenotype following focal cerebral ischemia. The MyD88 pathway directs the expression of neutrophil chemoattractants following cerebral ischemia.

  8. Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice

    Directory of Open Access Journals (Sweden)

    Nietfeld Wilfried

    2010-03-01

    Full Text Available Abstract Background The complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia. However, there is little information about the exact contribution of the membrane attack complex (MAC and its inhibitor-protein CD59. Methods Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO in young male and female CD59a knockout and wild-type mice. Two models of MCAO were applied: 60 min MCAO and 48 h reperfusion, as well as 30 min MCAO and 72 h reperfusion. CD59a knockout animals were compared to wild-type animals in terms of infarct size, edema, neurological deficit, and cell death. Results and Discussion CD59a-deficiency in male mice caused significantly increased infarct volumes and brain swelling when compared to wild-type mice at 72 h after 30 min-occlusion time, whereas no significant difference was observed after 1 h-MCAO. Moreover, CD59a-deficient mice had impaired neurological function when compared to wild-type mice after 30 min MCAO. Conclusion We conclude that CD59a protects against ischemic brain damage, but depending on the gender and the stroke model used.

  9. Memantine mediates neuroprotection via regulating neurovascular unit in a mouse model of focal cerebral ischemia.

    Science.gov (United States)

    Chen, Zheng-Zhen; Yang, Dan-Dan; Zhao, Zhan; Yan, Hui; Ji, Juan; Sun, Xiu-Lan

    2016-04-01

    Memantine is a low-moderate affinity and uncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist, which is also a potential neuroprotectant in acute ischemic stroke for its particular action profiles. The present study was to reveal the mechanisms involved in the neuroprotection of memantine. We used a mouse model of permanent focal cerebral ischemia via middle cerebral artery occlusion to verify our hypothesis. 2,3,5-Triphenyltetrazolium chloride staining was used to compare infarct size. The amount of astrocytes and the somal volume of the microglia cell body were analyzed by immunohistochemistry and stereological estimates. Western blotting was used to determine the protein expressions. Memantine prevented cerebral ischemia-induced brain infarct and neuronal injury, and reduced oxygen-glucose deprivation-induced cortical neuronal apoptosis. Moreover, memantine reduced the amount of the damaged astrocytes and over activated microglia after 24h of ischemia. In the early phase of ischemia, higher production of MMP-9 was observed, and thereby collagen IV was dramatically disrupted. Meanwhile, the post-synaptic density protein 95(PSD-95) was also severely cleavaged. Memantine decreased MMP-9 secretion, prevented the degradation of collagen IV in mouse brain. PSD-95 cleavage was also inhibited by memantine. These results suggested that memantine exerted neuroprotection effects in acute ischemic brain damage, partially via improving the functions of neurovascular unit. Taking all these findings together, we consider that memantine might be a promising protective agent against ischemic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Standards and pitfalls of focal ischemia models in spontaneously hypertensive rats: With a systematic review of recent articles

    Directory of Open Access Journals (Sweden)

    Yao Hiroshi

    2012-07-01

    Full Text Available Abstract We reviewed the early development of various focal ischemia models in spontaneously hypertensive rats (SHR, and summarized recent reports on this topic. Among 6 focal ischemia models established in divergent substrains of SHR, distal middle cerebral artery occlusion is the most frequently used and relevant method of focal ischemia in the light of penumbra concept. We performed an online PubMed search (2001–2010, and identified 118 original articles with focal ischemia in SHR. Physiological parameters such as age, body weight, and even blood pressure were often neglected in the literature: the information regarding the physiological parameters of SHR is critical, and should be provided within the methodology section of all articles related to stroke models in SHR. Although the quality of recent studies on neuroprotective strategy is improving, the mechanisms underlying the protection should be more clearly recognized so as to facilitate the translation from animal studies to human stroke. To overcome the genetic heterogeneity in substrains of SHR, new approaches, such as a huge repository of genetic markers in rat strains and the congenic strategy, are currently in progress.

  11. Neuroprotective mechanism of BNG-1 against focal cerebral ischemia: a neuroimaging and neurotrophin study.

    Science.gov (United States)

    Chi, Nai-Fang; Liu, Ho-Ling; Yang, Jen-Tsung; Lin, Jr-Rung; Liao, Shu-Li; Peng, Bo-Han; Lee, Yen-Tung; Lee, Tsong-Hai

    2014-01-01

    BNG-1 is a herb complex used in traditional Chinese medicine to treat stroke. In this study, we attempted to identify the neuroprotective mechanism of BNG-1 by using neuroimaging and neurotrophin analyses of a stroke animal model. Rats were treated with either saline or BNG-1 for 7 d after 60-min middle cerebral artery occlusion by filament model. The temporal change of magnetic resonance (MR) imaging of brain was studied using a 7 Tesla MR imaging (MRI) system and the temporal expressions of neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in brain were analyzed before operation and at 4 h, 2 d, and 7 d after operation. Compared with the saline group, the BNG-1 group exhibited a smaller infarction volume in the cerebral cortex in T2 image from as early as 4 h to 7 d, less edema in the cortex in diffusion weighted image from 2 to 7 d, earlier reduction of postischemic hyperperfusion in both the cortex and striatum in perfusion image at 4 h, and earlier normalization of the ischemic pattern in the striatum in susceptibility weighted image at 2 d. NT-3 and BDNF levels were higher in the BNG-1 group than the saline group at 7 d. We concluded that the protective effect of BNG-1 against cerebral ischemic injury might act through improving cerebral hemodynamics and recovering neurotrophin generation.

  12. Changes in brain levels of N-acylethanolamines and 2-arachidonoylglycerol in focal cerebral ischemia in mice

    DEFF Research Database (Denmark)

    Degn, Matilda; Lambertsen, Kate L; Petersen, Gitte

    2007-01-01

    cerebral ischemia and endogenous NAEs. Over the first 24 h after induction of permanent middle cerebral artery occlusion, we observed a time-dependent increase in all the investigated NAEs, except for anandamide. Moreover, we found an accumulation of 2-AG at 4 h that returned to basal level 12 h after.......5 h before arterial occlusion decreased the infarct volume in our model system. Our results suggest that NAEs and 2-AG may be involved in regulation of neuroprotection during focal cerebral ischemia in mice....

  13. Effects of dexmedetomidine on microregional O2 balance during reperfusion after focal cerebral ischemia.

    Science.gov (United States)

    Chi, Oak Z; Grayson, Jeremy; Barsoum, Sylviana; Liu, Xia; Dinani, Aliraza; Weiss, Harvey R

    2015-01-01

    This study was performed to determine whether there is an association between microregional O2 balance and neuronal survival in cerebral ischemia-reperfusion using dexmedetomidine, an α2-adrenoreceptor agonist and a sedative. Rats were subjected to 1 hour middle cerebral artery occlusion and a 2-hour reperfusion. During reperfusion, normal saline (n = 14) or dexmedetomidine 1 μg/kg/minute (n = 14) was infused intravenously. At 2 hours of reperfusion, regional cerebral blood flow using (14)C-iodoantipyrine autoradiography, microregional arterial and venous (20-60 μm in diameter) O2 saturation (SvO2) using cryomicrospectrophotometry, and the size of cortical infarction were determined. Ischemia-reperfusion decreased microregional SvO2 (52.9 ± 3.7% vs. 61.1 ± .6%, P < .005) with increased variation or heterogeneity (P < .0001) with similar regional cerebral blood flow and O2 consumption. Dexmedetomidine during reperfusion decreased the heterogeneity of SvO2 that was analyzed with an analysis of variance (P < .01) and reported as coefficient of variation (100 × standard deviation/Mean) (11.8 vs. 16.4). The number of veins with O2 saturation less than 50% decreased with dexmedetomidine (13/80 vs. 27/81, P < .01). The percentage of cortical infarct in total cortex was smaller with dexmedetomidine (8.3 ± 2.2% vs. 12.6 ± 1.5%, P < .005). In the cerebral ischemic reperfused cortex, dexmedetomidine decreased the heterogeneity of SvO2 and the number of small veins with low O2 saturation suggesting improved microregional O2 supply/consumption balance. The improvement was accompanied by the reduced size of cortical infarction. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Neuroprotective Activity of Lavender Oil on Transient Focal Cerebral Ischemia in Mice

    Directory of Open Access Journals (Sweden)

    Qiusheng Zheng

    2012-08-01

    Full Text Available The air-dried aerial parts of Lavandula angustifolia Mill, a traditional Uygur herbal drug, is used as resuscitation-inducing therapy to treat neurodisfunctions, such as stroke. This study was designed to assess the neuroprotective effects of lavender oil against ischemia/reperfusion (IR injury in mice. Focal cerebral ischemia was induced by the intraluminal occlusion method with a nylon string. The neurodysfuntion was evaluated by neurological deficit and the infarct area was showed by 2,3,5-triphenyltetrazolium chloride (TTC staining. The histopathological changes were observed by hematoxylin and eosin staining. The levels of mitochondria-generated reactive oxygen species (ROS, malondialdehyde (MDA and carbonyl, the ratio of reduced glutathione (GSH/glutathione disulfide (GSSG, the activities of superoxide dismutase (SOD, catalase (CAT and glutathion peroxidase (GSH-Px in brain tissue were measured to estimate the oxidative stress state. Neurological deficit, infarct size, histopathology changes and oxidative stress markers were evaluated after 22 h of reperfusion. In comparison with the model group, treatment with lavender oil significantly decreased neurological deficit scores, infarct size, the levels of MDA, carbonyl and ROS, and attenuated neuronal damage, upregulated SOD, CAT, GSH-Px activities and GSH/GSSG ratio. These results suggested that the neuroprotective effects of lavender oil against cerebral ischemia/reperfusion injury may be attributed to its antioxidant effects.

  15. Nicardipine reduces calcium accumulation and electrolyte derangements in regional cerebral ischemia in rats

    International Nuclear Information System (INIS)

    Hadani, M.; Young, W.; Flamm, E.S.

    1988-01-01

    We studied the effects of the calcium channel blocker nicardipine on regional tissue Ca 2+ , Na + , K + , and water shifts in the brains of seven Sprague-Dawley rats after permanent occlusions of the middle cerebral artery. We also assessed the entry of [ 14 C]nicardipine into the brains of five rats; the highest concentrations of [ 14 C]nicardipine were in the infarcted area. Nicardipine treatment significantly reduced Ca 2+ accumulation in the middle cerebral artery territory by 60% compared with six untreated rats 6 hours after arterial occlusion. Eight 125-micrograms/kg boluses of nicardipine given every 30 minutes starting 5 minutes after arterial occlusion also significantly reduced the Na + and K + shifts in the middle cerebral artery territory by 40% and 50%, respectively, 6 hours after arterial occlusion. Nicardipine appears to reduce Ca 2+ accumulation more than it reduces Na + and water accumulation and K + loss. Our results suggest that a calcium channel blocker can protect brain tissues in a model of focal cerebral infarction by directly reducing Ca 2+ entry into ischemic cells

  16. Hexane extracts of Polygonum multiflorum improve tissue and functional outcome following focal cerebral ischemia in mice.

    Science.gov (United States)

    Lee, Soo Vin; Choi, Kyung Ha; Choi, Young Whan; Hong, Jin Woo; Baek, Jin Ung; Choi, Byung Tae; Shin, Hwa Kyoung

    2014-04-01

    Polygonum multiflorum is a traditional Korean medicine that has been utilized widely in East Asian countries as a longevity agent. Clinical studies have demonstrated that Polygonum multiflorum improves hypercholesterolemia, coronary heart disease, neurosis and other diseases commonly associated with aging. However, scientific evidence defining the protective effects and mechanisms of Polygonum multiflorum against ischemic stroke is incomplete. In the present study, we investigated the cerebrovascular protective effects of Polygonum multiflorum against ischemic brain injury using an in vivo photothrombotic mouse model. To examine the underlying mechanism of action, we utilized an in vitro human brain microvascular endothelial cell (HBMEC) culture system. Hexane extracts (HEPM), ethyl acetate extracts (EAEPM) and methanol extracts (MEPM) of Polygonum multiflorum (100 mg/kg) were administered intraperitoneally 30 min prior to ischemic insult. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, as well as neurological and motor function, 24 h after ischemic brain injury. Following ischemic insult, HEPM induced a significant reduction in infarct volume and subsequent neurological deficits, compared with EAEPM and MEPM. HEPM significantly decreased infarct size and improved neurological and motor function, which was not observed in eNOS KO mice, suggesting that this cerebroprotective effect is primarily an eNOS-dependent mechanism. In vitro, HEPM effectively promoted NO production, however these effects were inhibited by the NOS inhibitor, L-NAME and the PI3K/Akt inhibitor, LY-294002. Furthermore, HEPM treatment resulted in increased phosphorylation-dependent activation of Akt and eNOS in HBMEC, suggesting that HEPM increased NO production via phosphorylation-dependent activation of Akt and eNOS. In conclusion, HEPM prevents cerebral

  17. Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice.

    Directory of Open Access Journals (Sweden)

    Hailong Yu

    Full Text Available Carvacrol (CAR, a naturally occurring monoterpenic phenol and food additive, has been shown to have antimicrobials, antitumor, and antidepressant-like activities. A previous study demonstrated that CAR has the ability to protect liver against ischemia/reperfusion injury in rats. In this study, we investigated the protective effects of CAR on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that CAR (50 mg/kg significantly reduced infarct volume and improved neurological deficits after 75 min of ischemia and 24 h of reperfusion. This neuroprotection was in a dose-dependent manner. Post-treatment with CAR still provided protection on infarct volume when it was administered intraperitoneally at 2 h after reperfusion; however, intracerebroventricular post-treatment reduced infarct volume even when the mice were treated with CAR at 6 h after reperfusion. These findings indicated that CAR has an extended therapeutic window, but delivery strategies may affect the protective effects of CAR. Further, we found that CAR significantly decreased the level of cleaved caspase-3, a marker of apoptosis, suggesting the anti-apoptotic activity of CAR. Finally, our data indicated that CAR treatment increased the level of phosphorylated Akt and the neuroprotection of CAR was reversed by a PI3K inhibitor LY-294002, demonstrating the involvement of the PI3K/Akt pathway in the anti-apoptotic mechanisms of CAR. Due to its safety and wide use in the food industry, CAR is a promising agent to be translated into clinical trials.

  18. Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning

    Science.gov (United States)

    Ren, Chuancheng; Gao, Xuwen; Steinberg, Gary K.; Zhao, Heng

    2009-01-01

    Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 minute occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 minute occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for 2 or 3 cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with 3 cycles of 15 minutes performed immediately before stroke reduced infarct size from 47.7±7.6% of control ischemia to 9.8±8.6%; at 2 cycles of 15 minutes, infarct was reduced to 24.7±7.3%; at 2 cycles of 5 minutes, infarct was not reduced. Delayed preconditioning with 3 cycles of 15 minutes conducted 2 days before stroke also reduced infarct to 23.0 ±10.9%, but with 2 cycles of 15 minutes it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with 3 cycles of 15 minutes performed 12 hours before stroke also reduced infarct to 24.7±4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia. PMID:18201834

  19. Sodium phenylbutyrate ameliorates focal cerebral ischemic/reperfusion injury associated with comorbid type 2 diabetes by reducing endoplasmic reticulum stress and DNA fragmentation.

    Science.gov (United States)

    Srinivasan, Krishnamoorthy; Sharma, Shyam S

    2011-11-20

    Endoplasmic reticulum (ER) stress has been postulated to play a crucial role in the pathophysiology of cerebral ischemic/reperfusion (I/R) injury and diabetes. Diabetes is a major risk factor and also common amongst the people who suffer from stroke. In this study, we have investigated the neuroprotective potential of sodium 4-phenylbutyrate (SPB; 30-300mg/kg), a chemical chaperone by targeting ER stress in a rat model of transient focal cerebral ischemia associated with comorbid type 2 diabetes. Intraperitoneal treatment with SPB (100 and 300mg/kg) significantly ameliorated brain I/R damage as evidenced by reduction in cerebral infarct and edema volume. It also significantly improved the functional recovery of various neurobehavioral impairments (neurological deficit score, grip strength and rota rod) evoked by I/R compared with vehicle-treatment. Further, SPB (100mg/kg) significantly reduced the DNA fragmentation as shown by prominent reduction in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells. This effect was observed concomitantly with significant attenuation in upregulation of 78kDa glucose regulated protein (GRP78), CCAAT/enhancer binding protein homologous protein or growth arrest DNA damage-inducible gene 153 (CHOP/GADD153) and activation of caspase-12, specific markers of ER stress/apoptosis. The neuroprotection observed with SPB was independent of its effect on cerebral blood flow and blood glucose. In conclusion, this study demonstrates the neuroprotective effect of SPB owing to amelioration of ER stress and DNA fragmentation. It also suggest that targeting ER stress might offer a promising therapeutic approach and benefits against ischemic stroke associated with comorbid type 2 diabetes. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Neuroprotective effect of safranal, an active ingredient of Crocus sativus , in a rat model of transient cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Hamid R. Sadeghnia

    2017-09-01

    Full Text Available Safranal is a monoterpene aldehyde found in saffron (Crocus sativus L. petals. It has been previously reported that safranal has a wide range of activities such as antioxidant and anti-inflammatory effects. In this study, we examined the effect of safranal on brain injuries in a transient model of focal cerebral ischemia. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min, followed by 24 h of reperfusion. Safranal in the doses of 72.5 and 145 mg/kg was administered intraperitoneally at 0, 3, and 6 h after reperfusion. Neurobehavioral deficit, infarct volume, hippocampal cell loss and markers of oxidative stress including thiobarbituric acid reactive substances (TBARS, total sulfhydryl (SH content, and antioxidant capacity (using FRAP assay were also assessed. The focal cerebral ischemia induced a significant increase in the neurological score, infarct volume and neuronal cell loss in the ipsilateral hippocampal CA1 and CA3 subfields (p < 0.001 and also oxidative stress markers (p < 0.01. Following safranal administration, the total SH content and antioxidant capacity significantly increased, while marked decreases were observed in the neurological score, infarct volume and hippocampal cell loss, as well as TBARS level. This study concluded that safranal had protective effects on ischemic reperfusion injury in the rat model of stroke. Such effects of safranal may have been exerted mainly by suppressing the production of free radicals and increasing antioxidant activity.

  1. Housing conditions influence motor functions and exploratory behavior following focal damage of the rat brain.

    Science.gov (United States)

    Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna

    2009-01-01

    The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.

  2. Effect of thuringiensin on adenylate cyclase in rat cerebral cortex

    International Nuclear Information System (INIS)

    Tsai, S.-F.; Yang Chi; Wang, S.-C.; Wang, J.-S.; Hwang, J.-S.; Ho, S.-P.

    2004-01-01

    The purpose of this work is to evaluate the effect of thuringiensin on the adenylate cyclase activity in rat cerebral cortex. The cyclic adenosine 3'5'-monophosphate (cAMP) levels were shown to be dose-dependently elevated 17-450% or 54-377% by thuringiensin at concentrations of 10 μM-100 mM or 0.5-4 mM, due to the activation of basal adenylate cyclase activity of rat cerebral cortical membrane preparation. Thuringiensin also activated basal activity of a commercial adenylate cyclase from Escherichia coli. However, the forskolin-stimulated adenylate cyclase activity in rat cerebral cortex was inhibited by thuringiensin at concentrations of 1-100 μM, thus cAMP production decreased. Furthermore, thuringiensin or adenylate cyclase inhibitor (MDL-12330A) reduced the forskolin (10 μM)-stimulated adenylate cyclase activity at concentrations of 10 μM, 49% or 43% inhibition, respectively. In conclusion, this study demonstrated that thuringiensin could activate basal adenylate cyclase activity and increase cAMP concentrations in rat cerebral cortex or in a commercial adenylate cyclase. Comparing the dose-dependent effects of thuringiensin on the basal and forskolin-stimulated adenylate cyclase activity, thuringiensin can be regarded as a weak activator of adenylate cyclase or an inhibitor of forskolin-stimulated adenylate cyclase

  3. Simulation of a conductive shield plate for the focalization of transcranial magnetic stimulation in the rat.

    Science.gov (United States)

    Gasca, Fernando; Richter, Lars; Schweikard, Achim

    2010-01-01

    Transcranial Magnetic Stimulation (TMS) in the rat is a powerful tool for investigating brain function. However, the state-of-the-art experiments are considerably limited because the stimulation usually affects undesired anatomical structures. A simulation of a conductive shield plate placed between the coil stimulator and the rat brain during TMS is presented. The Finite Element (FE) method is used to obtain the 3D electric field distribution on a four-layer rat head model. The simulations show that the shield plate with a circular window can improve the focalization of stimulation, as quantitatively seen by computing the three-dimensional half power region (HPR). Focalization with the shield plate showed a clear compromise with the attenuation of the induced field. The results suggest that the shield plate can work as a helpful tool for conducting TMS rat experiments on specific targets.

  4. The free radical spin-trap alpha-PBN attenuates periinfarct depolarizations following permanent middle cerebral artery occlusion in rats without reducing infarct volume

    DEFF Research Database (Denmark)

    Christensen, Thomas; Bruhn, Torben; Diemer, Nils Henrik

    2003-01-01

    The effect of the free radical spin-trap alpha-phenyl-butyl-tert-nitrone (alpha-PBN) in permanent focal cerebral ischemia in rats was examined in two series of experiments. In the first, rats were subjected to permanent occlusion of the middle cerebral artery (MCAO) and treated 1 h after occlusion...... with a single dose of alpha-PBN (100 mg/kg) or saline. Body temperature was measured and controlled for the first 24 h to obtain identical temperature curves in the two groups. Cortical infarct volumes were determined on histological sections 7 days later. alpha-PBN did not significantly reduce infarct volume...

  5. Protective effects of alkaloid extract from Leonurus heterophyllus on cerebral ischemia reperfusion injury by middle cerebral ischemic injury (MCAO) in rats.

    Science.gov (United States)

    Liang, Hao; Liu, Ping; Wang, Yunshan; Song, Shuliang; Ji, Aiguo

    2011-07-15

    The neuronal damage following cerebral ischemia is a serious risk to stroke patients. The aim of this study was to investigate the neuroprotective effects of alkaloid extract from Leonurus heterophyllus (LHAE) on cerebral ischemic injury. After 24 h of reperfusion following ischemia for 2 h induced by middle cerebral artery occlusion (MCAO), some rats were intraperitoneally administered different doses of LHAE (3.6, 7.2, 14.4 mg/kg, respectively). Neurological examination was measured in all animals. Infarct volume, myeloperoxidase (MPO) activity, levels of nitrate/nitrite metabolite (NO) and apoptosis ratio of nerve fiber in brain were determined. The results showed that LHAE at 7.2 mg/kg or 14.4 mg/kg exerted significantly decreasing neurological deficit scores and reducing the infarct volume on rats with focal cerebral ischemic injury (pagent. Further studies are warranted to assess the efficacy and safety of LHAE in patients. Copyright © 2011 Elsevier GmbH. All rights reserved.

  6. Hyperexpressed netrin-1promoted neural stem cells migration in mice after focal cerebral ischemia

    OpenAIRE

    Haiyan Lu; Xiaoyan Song; Feng Wang; Guodong Wang; Yuncheng Wu; Qiaoshu Wang; Yongting Wang; Guoyuan Yang; Zhijun Zhang

    2016-01-01

    Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent ...

  7. Induction profile of MANF/ARMET by cerebral ischemia and its implication for neuron protection

    OpenAIRE

    Yu, Yong-Qiang; Liu, Lian-Cheng; Wang, Fa-Cai; Liang, Yan; Cha, Da-Qin; Zhang, Jing-Jing; Shen, Yu-Jun; Wang, Hai-Ping; Fang, Shengyun; Shen, Yu-Xian

    2009-01-01

    Cerebral ischemia-induced accumulation of unfolded proteins in vulnerable neurons triggers endoplasmic reticulum (ER) stress. Arginine-rich, mutated in early stage tumors (ARMET) is an ER stress-inducible protein and upregulated in the early stage of cerebral ischemia. The purposes of this study were to investigate the characteristics and implications of ARMET expression induced by focal cerebral ischemia. Focal cerebral ischemia in rats was induced by right middle cerebral artery occlusion w...

  8. Enhanced expressions of microvascular smooth muscle receptors after focal cerebral ischemia occur via the MAPK MEK/ERK pathway

    DEFF Research Database (Denmark)

    Maddahi, A.; Edvinsson, L.

    2008-01-01

    ), the enhanced vascular receptor expression, and attenuated the cerebral infarct and improved neurology score. CONCLUSION: Our results show that MCAO results in upregulation of cerebrovascular ETB, AT1 and 5-HT1B receptors. Blockade of this event with a MEK1 inhibitor as late as 6 h after the insult reduced...... the role of the MEK/ERK pathway in receptor expression following ischemic brain injury using the specific MEK1 inhibitor U0126. METHODS AND RESULT: Rats were subjected to a 2-h middle cerebral artery occlusion (MCAO) followed by reperfusion for 48-h and the ischemic area was calculated. The expression...... of phosphorylated ERK1/2 and Elk-1, and of endothelin ETA and ETB, angiotensin AT1, and 5-hydroxytryptamine 5-HT1B receptors were analyzed with immunohistochemistry using confocal microscopy in cerebral arteries, microvessels and in brain tissue. The expression of endothelin ETB receptor was analyzed...

  9. [Identification of early irreversible damage area in a rat model of cerebral ischemia and reperfusion].

    Science.gov (United States)

    Liu, S; Guo, Y

    2000-02-01

    To observe the early neuron ischemic damage in focal cerebral ischemia/reperfusion with histostaining methods of argyrophil III (AG III), Toludine blue(TB), and H&E, and to make out the 'separating line' between the areas of reversible and irreversible early ischemic damage. Forty-two male Wistar rats were randomly divided into the following groups: pseudo-surgical, blank-control, O2R0(occluded for 2 hours and reperfused for 0 hour), O2R0.5, O2R2, O2R4, O2R24. There were 6 rats in each group. Rats in experimental groups were suffered focal cerebral ischemia/reperfusion through a nylon suture method. After a special processor for tissue manage, the brain were coronal sectioned and stained with H&E, TB, and AG III. The area where dark neurons dwell in (ischemic core) were calculated with image analysis system. The success rate of ischemic model for this experiment is 90%. After being stained with argyrophil III method, normal neurons appear yellow or pale brown, which is hardly distinguished from the pale brown background. The ischemic neuron stained black, and has collapsed body and "corkscrew-like" axon or dentries, which were broken to some extent. The neuropil in the dark neurons dwelt area appears gray or pale black, which is apparently different from the pale brown neighborhood area. The distribution of dark neurons in cortex varies according to different layers, and has a character of columnar form. The dark neurons present as early as 2 hours ischemia without reperfusion with AG III method. AG III stain could selectively display early ischemic neurons, the area dwelt by dark neurons represent early ischemic core. Dark neuron is possibly the irreversibly damaged neuron. Identification of dark neurons could be helpful in the discrimination between early ischemic center and penumbra.

  10. Metabolite changes in the ipsilateral and contralateral cerebral hemispheres in rats with middle cerebral artery occlusion

    Directory of Open Access Journals (Sweden)

    Lei Ruan

    2017-01-01

    Full Text Available Cerebral ischemia not only causes pathological changes in the ischemic areas but also induces a series of secondary changes in more distal brain regions (such as the contralateral cerebral hemisphere. The impact of supratentorial lesions, which are the most common type of lesion, on the contralateral cerebellum has been studied in patients by positron emission tomography, single photon emission computed tomography, magnetic resonance imaging and diffusion tensor imaging. In the present study, we investigated metabolite changes in the contralateral cerebral hemisphere after supratentorial unilateral ischemia using nuclear magnetic resonance spectroscopy-based metabonomics. The permanent middle cerebral artery occlusion model of ischemic stroke was established in rats. Rats were randomly divided into the middle cerebral artery occlusion 1-, 3-, 9- and 24-hour groups and the sham group. 1H nuclear magnetic resonance spectroscopy was used to detect metabolites in the left and right cerebral hemispheres. Compared with the sham group, the concentrations of lactate, alanine, γ-aminobutyric acid, choline and glycine in the ischemic cerebral hemisphere were increased in the acute stage, while the concentrations of N-acetyl aspartate, creatinine, glutamate and aspartate were decreased. This demonstrates that there is an upregulation of anaerobic glycolysis (shown by the increase in lactate, a perturbation of choline metabolism (suggested by the increase in choline, neuronal cell damage (shown by the decrease in N-acetyl aspartate and neurotransmitter imbalance (evidenced by the increase in γ-aminobutyric acid and glycine and by the decrease in glutamate and aspartate in the acute stage of cerebral ischemia. In the contralateral hemisphere, the concentrations of lactate, alanine, glycine, choline and aspartate were increased, while the concentrations of γ-aminobutyric acid, glutamate and creatinine were decreased. This suggests that there is a

  11. Early Exercise Protects against Cerebral Ischemic Injury through Inhibiting Neuron Apoptosis in Cortex in Rats

    Directory of Open Access Journals (Sweden)

    Junfa Wu

    2013-03-01

    Full Text Available Early exercise is an effective strategy for stroke treatment, but the underlying mechanism remains poorly understood. Apoptosis plays a critical role after stroke. However, it is unclear whether early exercise inhibits apoptosis after stroke. The present study investigated the effect of early exercise on apoptosis induced by ischemia. Adult SD rats were subjected to transient focal cerebral ischemia by middle cerebral artery occlusion model (MCAO and were randomly divided into early exercise group, non-exercise group and sham group. Early exercise group received forced treadmill training initiated at 24 h after operation. Fourteen days later, the cell apoptosis were detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL and Fluoro-Jade-B staining (F-J-B. Caspase-3, cleaved caspase-3 and Bcl-2 were determined by western blotting. Cerebral infarct volume and motor function were evaluated by cresyl violet staining and foot fault test respectively. The results showed that early exercise decreased the number of apoptotic cells (118.74 ± 6.15 vs. 169.65 ± 8.47, p < 0.05, n = 5, inhibited the expression of caspase-3 and cleaved caspase-3 (p < 0.05, n = 5, and increased the expression of Bcl-2 (p < 0.05, n = 5. These data were consistent with reduced infarct volume and improved motor function. These results suggested that early exercise could provide neuroprotection through inhibiting neuron apoptosis.

  12. Effects of focal lesions produced by beta irradiating the cerebellums in fetal and infant rats

    International Nuclear Information System (INIS)

    Pulliam, J.A.

    1976-01-01

    A beam of beta radiation, 2mm in diameter, was used to irradiate the cerebellum in 29 rat fetuses and in 90 infant rats and to irradiate the cerebrum in 51 rat fetuses and in 72 infant rats. The age range of the rats was from the 15th fetal day to the 6th postnatal day. Localized beta radiation produced lesions limited to the cerebrum, to the cerebellum, to one cerebral hemisphere, or to one cerebellar hemisphere and the vermis in rat fetes and in infant rats. Varying degrees of ataxia were produced in the irradiated rats. This ataxia was proportional to the hypoplasia of the cerebellum. Severe reduction in the size of the cerebrum caused no motor deficits. The lesions produced by localized beta radiation were similar to lesions produced by x radiation, except that beta radiation produced lesions that were more localized and that were asymmetrical. Also the beta radiation offered the investigator more flexibility in selecting the site of the lesion regardless to the age of the rat fetus or the infant rat

  13. Hyperthermia induced after recirculation triggers chronic neurodegeneration in the penumbra zone of focal ischemia in the rat brain

    Directory of Open Access Journals (Sweden)

    L.A. Favero-Filho

    2008-11-01

    Full Text Available Chronic neurodegenerative processes have been identified in the rat forebrain after prolonged survival following hyperthermia (HT initiated a few hours after transient global ischemia. Since transient global ischemia and ischemic penumbra share pathophysiological similarities, this study addressed the effects of HT induced after recirculation of focal brain ischemia on infarct size during long survival times. Adult male Wistar rats underwent intra-luminal occlusion of the left middle cerebral artery for 60 min followed by HT (39.0-39.5°C or normothermia. Control procedures included none and sham surgery with and without HT, and middle cerebral artery occlusion alone. Part I: 6-h HT induced at recirculation. Part II: 2-h HT induced at 2-, 6-, or 24-h recirculation. Part III: 2-h HT initiated at recirculation or 6-h HT initiated at 2-, 6- or 24-h recirculation. Survival periods were 7 days, 2 or 6 months. The effects of post-ischemic HT on cortex and striatum were evaluated histopathologically by measuring the area of remaining tissue in the infarcted hemisphere at -0.30 mm from bregma. Six-hour HT initiated from 6-h recirculation caused a significant decrease in the remaining cortical tissue between 7-day (N = 8 and 2-month (N = 8 survivals (98.46 ± 1.14 to 73.62 ± 8.99%, respectively. When induced from 24-h recirculation, 6-h HT caused a significant reduction of the remaining cortical tissue between 2- (N = 8 and 6-month (N = 9 survivals (94.97 ± 5.02 vs 63.26 ± 11.97%, respectively. These data indicate that post-ischemic HT triggers chronic neurodegenerative processes in ischemic penumbra, suggesting that similar fever-triggered effects may annul the benefit of early recirculation in stroke patients over the long-term.

  14. Enhanced expressions of microvascular smooth muscle receptors after focal cerebral ischemia occur via the MAPK MEK/ERK pathway

    Directory of Open Access Journals (Sweden)

    Edvinsson Lars

    2008-09-01

    Full Text Available Abstract Background MEK1/2 is a serine/threonine protein that phosphorylates extracellular signal-regulated kinase (ERK1/2. Cerebral ischemia results in enhanced expression of cerebrovascular contractile receptors in the middle cerebral artery (MCA leading to the ischemic region. Here we explored the role of the MEK/ERK pathway in receptor expression following ischemic brain injury using the specific MEK1 inhibitor U0126. Methods and result Rats were subjected to a 2-h middle cerebral artery occlusion (MCAO followed by reperfusion for 48-h and the ischemic area was calculated. The expression of phosphorylated ERK1/2 and Elk-1, and of endothelin ETA and ETB, angiotensin AT1, and 5-hydroxytryptamine 5-HT1B receptors were analyzed with immunohistochemistry using confocal microscopy in cerebral arteries, microvessels and in brain tissue. The expression of endothelin ETB receptor was analyzed by quantitative Western blot. We demonstrate that there is an increase in the number of contractile smooth muscle receptors in the MCA and in micro- vessels within the ischemic region. The enhanced expression occurs in the smooth muscle cells as verified by co-localization studies. This receptor upregulation is furthermore associated with enhanced expression of pERK1/2 and of transcription factor pElk-1 in the vascular smooth muscle cells. Blockade of transcription with the MEK1 inhibitor U0126, given at the onset of reperfusion or as late as 6 hours after the insult, reduced transcription (pERK1/2 and pElk-1, the enhanced vascular receptor expression, and attenuated the cerebral infarct and improved neurology score. Conclusion Our results show that MCAO results in upregulation of cerebrovascular ETB, AT1 and 5-HT1B receptors. Blockade of this event with a MEK1 inhibitor as late as 6 h after the insult reduced the enhanced vascular receptor expression and the associated cerebral infarction.

  15. Radiation dose reduction without compromise to image quality by alterations of filtration and focal spot size in cerebral angiography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Joon; Park, Min Keun; Jung, Da Eun; Kang, Jung Han; Kim, Byung Moon [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2017-08-01

    Different angiographic protocols may influence the radiation dose and image quality. In this study, we aimed to investigate the effects of filtration and focal spot size on radiation dose and image quality for diagnostic cerebral angiography using an in-vitro model and in-vivo patient groups. Radiation dose and image quality were analyzed by varying the filtration and focal spot size on digital subtraction angiography exposure protocols (1, inherent filtration + large focus; 2, inherent + small; 3, copper + large; 4, copper + small). For the in-vitro analysis, a phantom was used for comparison of radiation dose. For the in-vivo analysis, bilateral paired injections, and patient cohort groups were compared for radiation dose and image quality. Image quality analysis was performed in terms of contrast, sharpness, noise, and overall quality. In the in-vitro analysis, the mean air kerma (AK) and dose area product (DAP)/frame were significantly lower with added copper filtration (protocols 3 and 4). In the in-vivo bilateral paired injections, AK and DAP/frame were significantly lower with filtration, without significant difference in image quality. The patient cohort groups with added filtration (protocols 3 and 4) showed significant reduction of total AK and DAP/patient without compromise to the image quality. Variations in focal spot size showed no significant differences in radiation dose and image quality. Addition of filtration for angiographic exposure studies can result in significant total radiation dose reduction without loss of image quality. Focal spot size does not influence radiation dose and image quality. The routine angiographic protocol should be judiciously investigated and implemented.

  16. Evaluation of technetium-99m exametazime stabilised with cobalt chloride as a blood flow tracer in focal cerebral ischaemia

    Energy Technology Data Exchange (ETDEWEB)

    Gartshore, G [Wellcome Surgical Inst. and Hugh Fraser Neuroscience Labs., Glasgow Univ. (United Kingdom); Bannan, P [Wellcome Surgical Inst. and Hugh Fraser Neuroscience Labs., Glasgow Univ. (United Kingdom); Patterson, J [Wellcome Surgical Inst. and Hugh Fraser Neuroscience Labs., Glasgow Univ. (United Kingdom); Higley, B [Wellcome Surgical Inst. and Hugh Fraser Neuroscience Labs., Glasgow Univ. (United Kingdom); McCulloch, J [Wellcome Surgical Inst. and Hugh Fraser Neuroscience Labs., Glasgow Univ. (United Kingdom)

    1994-09-01

    A protocol has been devised to effectively extend the limited post-reconstitution shelf life of technetium-99m exametazime as a radiopharmaceutical for imaging cerebral blood flow (CBF) distribution. The potential of [sup 99m]Tc-exametazime stabilised with cobalt chloride for imaging CBF distribution as late as 4 h after reconstitution has been examined in ischaemic and non-ischaemic tissue in halothane-anaesthetised cats. Focal cerebral ischaemia was produced by permanent middle cerebral artery occlusion. The relationship between [sup 99m]Tc-exametazime uptake and retention and CBF (assessed with [[sup 14]C]iodoantipyrine 10 min after first radiopharmaceutical administration) was determined in the same tissue section with double label autoradiography. Over the CBF range 0 - 80 ml 100 g[sup -1] min[sup -1], the uptake of [sup 99m]Tc-exametazime (quantitatively and topographically) was linearly related to CBF irrespective of whether the [sup 99m]Tc-labelled tracer was unstabilised (and administered within 10 min of reconstitution) or was stabilised with cobalt chloride (and administered up to 240 min after reconstitution). For levels of CBF in excess of 80 ml 100 g[sup -1] min[sup -1] the excellent topographical relationship between [sup 99m]Tc-exametazime distribution and CBF is maintained but quantitatively, [sup 99m]Tc-exametazime underestimates CBF to a similar degree in animals receiving stabilised and unstabilised [sup 99m]Tc-exametazime. The presence of the stabiliser, cobalt chloride, extends greatly the period over which [sup 99m]Tc-exametazime can be used after reconstitution to generate images of CBF distribution in normal and ischaemic cerebral tissue. (orig.)

  17. Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

    Science.gov (United States)

    Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.

    1990-01-01

    Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat

  18. Effect of focal irradiation on plasma kallikrein activity in tumor bearing rats

    International Nuclear Information System (INIS)

    Makoyo, P.O.Z.R.; West, W.L.

    1977-01-01

    The activated plasma kallikrein from tumor bearing rats before and after focal irradiation of the hind limbs was measured by the hydrolysis of 0.015M N-(p-toluene sulfonyl)-L arginine methyl ester (TAME). Blood was collected from abdominal aorta of rats anesthetized with diethyl ether into plastic tubes containing 1 volume of 3.8 percent sodium citrate for each 9 volumes. Plasma was isolated by centrifugation (2000 g) at 4 0 C. Small pieces of minced tumor tissue were inserted in a trochar and inoculated in the hind limbs of the rats. Morris hepatomas 7777 and 3924A were transplanted subcutaneously over the hind legs while Walker 256 tumor was transplanted intramuscularly in the hind limbs. Plasma kallikrein (μm TAME utilized/ml/hr) was decreased in three different groups of tumor bearing rats: Walker tumor from 207 +- 34 to 114 +- 30 Hepatoma 7777 from 219 +- 13 to 106 +- 3 and Hepatoma 3924A from 227 +- 7 to 133 +- 5. Two hours after focal irradiation (1000 R) plasma kallikrein decreased further in Walker tumor and hepatoma 7777 to 55 +- 5 and 96 +- 3.6 respectively. The plasma of tumor bearing rats becomes deficient in kallikrein at about the time metastases may be identified. The acute fall in plasma kallikrein is consistent with the overall stress mechanism

  19. Systemic focal epileptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Marcussen, W.H.

    1986-01-01

    Rats that receive radiation to 0.25 cc of one cerebral hemisphere are clinically and electroencephalographically normal until there is a breakdown of the blood-brain barrier (BBB) at 3 to 6 months postradiation. This BBB lesion can be detected by transient focal seizure activity produced by the BBB-excluded systemic convulsant bicuculline methiodide. In two rats the seizure activity induced by this one injection was self-sustaining. In seven of 15 other rats tested, the subsequent administration of repeated 2 mg/kg injections created a chronic focus that continued to spike with great frequency for 3 weeks or more without further administration of any convulsant. In three of eight other rats, implanted minipumps delivering 180 micrograms/h of bicuculline methiodide produced self-sustaining epileptic activity.

  20. Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Magata, Yasuhiro; Kitano, Haruhiro; Shiozaki, Toshiki; Iida, Yasuhiko; Nishizawa, Sadahiko; Saji, Hideo; Konishi, Junji

    2000-01-01

    The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3 H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125 I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions

  1. Focal increase of cerebral blood flow during stereognostic testing in man

    DEFF Research Database (Denmark)

    Roland, E; Larsen, B

    1976-01-01

    An attempt was made to study the regional cerebral blood flow (rCBF) pattern during stereognostic discrimination in man. The rCBF was measured in 18 subjects who had no major neurological defects. The clearance from the hemisphere of xenon 133 injected (133Xe) into the carotid artery was measured...

  2. Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor κB p65 activation

    International Nuclear Information System (INIS)

    Xue, Xia; Qu, Xian-Jun; Yang, Ying; Sheng, Xie-Huang; Cheng, Fang; Jiang, E-Nang; Wang, Jian-hua; Bu, Wen; Liu, Zhao-Ping

    2010-01-01

    Research highlights: → Permanent NF-κB p65 activation contributes to the infarction after ischemia-reperfusion injury in rats. → Baicalin can markedly inhibit the nuclear NF-κB p65 expression and m RNA levels after ischemia-reperfusion injury in rats. → Baicalin decreased the cerebral infarction area via inhibiting the activation of nuclear NF-κB p65. -- Abstract: Baicalin is a flavonoid compound purified from plant Scutellaria baicalensis Georgi. We aimed to evaluate the neuroprotective effects of baicalin against cerebral ischemic reperfusion injury. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. Baicalin at doses of 50, 100 and 200 mg/kg was intravenously injected after ischemia onset. Twenty-four hours after reperfusion, the neurological deficit was scored and infarct volume was measured. Hematoxylin and eosin (HE) staining was performed to analyze the histopathological changes of cortex and hippocampus neurons. We examined the levels of NF-κB p65 in ischemic cortexes by Western blot analysis and RT-PCR assay. The results showed that the neurological deficit scores were significantly decreased from 2.0 ± 0.7 to 1.2 ± 0.4 and the volume of infarction was reduced by 25% after baicalin injection. Histopathological examination showed that the increase of neurons with pycnotic shape and condensed nuclear in cortex and hippocampus were not observed in baicalin treated animals. Further examination showed that NF-κB p65 in cortex was increased after ischemia reperfusion injury, indicating the molecular mechanism of ischemia reperfusion injury. The level of NF-κB p65 was decreased by 73% after baicalin treatment. These results suggest that baicalin might be useful as a potential neuroprotective agent in stroke therapy. The neuroprotective effects of baicalin may relate to inhibition of NF-κB p65.

  3. Edaravone, a Free Radical Scavenger, Mitigates Both Gray and White Matter Damages after Global Cerebral Ischemia in Rats

    Science.gov (United States)

    Kubo, Kozue; Nakao, Shinichi; Jomura, Sachiko; Sakamoto, Sachiyo; Miyamoto, Etsuko; Xu, Yan; Tomimoto, Hidekazu; Inada, Takefumi; Shingu, Koh

    2012-01-01

    Recent studies have shown that similar to cerebral gray matter (mainly composed of neuronal perikarya), white matter (composed of axons and glias) is vulnerable to ischemia. Edaravone, a free radical scavenger, has neuroprotective effects against focal cerebral ischemia even in humans. In this study, we investigated the time course and the severity of both gray and white matter damage following global cerebral ischemia by cardiac arrest, and examined whether edaravone protected the gray and the white matter. Male Sprague-Dawley rats were used. Global cerebral ischemia was induced by 5 minutes of cardiac arrest and resuscitation (CAR). Edaravone, 3 mg/kg, was administered intravenously either immediately or 60 minutes after CAR. The morphological damage was assessed by cresyl violet staining. The microtubule-associated protein 2 (a maker of neuronal perikarya and dendrites), the β amyloid precursor protein (the accumulation of which is a maker of axonal damage), and the ionized calcium binding adaptor molecule 1 (a marker of microglia) were stained for immunohistochemical analysis. Significant neuronal perikaryal damage and marked microglial activation were observed in the hippocampal CA1 region with little axonal damage one week after CAR. Two weeks after CAR, the perikaryal damage and microglial activation were unchanged, but obvious axonal damage occurred. Administration of edaravone 60 minutes after CAR significantly mitigated the perikaryal damage, the axonal damage, and the microglial activation. Our results show that axonal damage develops slower than perikaryal damage and that edaravone can protect both gray and white matter after CAR in rats. PMID:19410562

  4. The effect of S. pneumoniae bacteremia on cerebral blood flow autoregulation in rats

    DEFF Research Database (Denmark)

    Pedersen, Michael; Brandt, Christian T.; Knudsen, Gitte Moos

    2008-01-01

    during incremental reductions in cerebral perfusion pressure (CPP) by controlled hemorrhage. Autoregulation was preserved in all rats without meningitis (groups A and E) and was lost in 24 of 25 meningitis rats (groups B, C, and D) (P

  5. Netrin-1 overexpression promotes white matter repairing and remodeling after focal cerebral ischemia in mice

    OpenAIRE

    He, Xiaosong; Li, Yaning; Lu, Haiyan; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

    2013-01-01

    Damage of oligodendrocytes after ischemia has negative impact on white matter integrity and neuronal function. In this work, we explore whether Netrin-1 (NT-1) overexpression facilitates white matter repairing and remodeling. Adult CD-1 mice received stereotactic injection of adeno-associated virus carrying NT-1 gene (AAV-NT-1). One week after gene transfer, mice underwent 60 minutes of middle cerebral artery occlusion. The effect of NT-1 on neural function was evaluated by neurobehavioral te...

  6. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Miyanohara, Jun [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Shirakawa, Hisashi, E-mail: shirakaw@pharm.kyoto-u.ac.jp [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Sanpei, Kazuaki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Nakagawa, Takayuki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital (Japan); Kaneko, Shuji [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan)

    2015-11-20

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca{sup 2+} permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

  7. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

    International Nuclear Information System (INIS)

    Miyanohara, Jun; Shirakawa, Hisashi; Sanpei, Kazuaki; Nakagawa, Takayuki; Kaneko, Shuji

    2015-01-01

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca"2"+ permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

  8. Profiles of cortical tissue depolarization in cat focal cerebral ischemia in relation to calcium ion homeostasis and nitric oxide production.

    Science.gov (United States)

    Ohta, K; Graf, R; Rosner, G; Heiss, W D

    1997-11-01

    Cortical depolarization was investigated in a topographic gradient of ischemic density after 1-hour transient middle cerebral artery occlusion in halothane-anesthetized cats. A laser Doppler flow probe, an ion-selective microelectrode, and a nitric oxide (NO) electrode measured regional CBF (rCBF), direct current (DC) potential, extracellular Ca2+ concentration ([Ca2+]o), and NO concentration in ectosylvian and suprasylvian gyri of nine animals. Recordings revealed 12 of 18 sites with persistent negative shifts of the DC potential, severe rCBF reduction, and a drop of [Ca2+]o characteristic for core regions of focal ischemia. Among these sites, two types were distinguished by further analysis. In Type 1 (n = 5), rapid, negative DC shifts resembled anoxic depolarization as described for complete global ischemia. In this type, ischemia was most severe (8.9 +/- 2.5% of control rCBF), [Ca2+]o dropped fast and deepest (0.48 +/- 0.20 mmol/L), and NO concentration increased transiently (36.1 +/- 24.0 nmol/L at 2.5 minutes), and decreased thereafter. In Type 2 (n = 7), the DC potential fell gradually over the first half of the ischemic episode, rCBF and [Ca2+]o reductions were smaller than in Type 1 (16.2 +/- 8.2%; 0.77 +/- 0.41 mmol/L), and NO increased continuously during ischemia (53.1 +/- 60.4 nmol/L at 60 minutes) suggesting that in this type NO most likely exerts its diverse actions on ischemia-threatened tissue. In the remaining six recording sites, a third type (Type 3) attributable to the ischemic periphery was characterized by minimal DC shifts, mild ischemia (37.2 +/- 13.3%), nonsignificant alterations of [Ca2+]o, but decreased NO concentrations during middle cerebral artery occlusion. Reperfusion returned the various parameters to baseline levels within 1 hour, the recovery of [Ca2+]o and NO concentration being delayed in Type 1. An NO synthase inhibitor (N(G)-nitro-L-arginine, 50 mg/kg intravenously; four animals) abolished NO elevation during ischemia. In

  9. Astragaloside IV for Experimental Focal Cerebral Ischemia: Preclinical Evidence and Possible Mechanisms

    Directory of Open Access Journals (Sweden)

    Hui-Lin Wang

    2017-01-01

    Full Text Available Astragaloside IV (AST-IV is a principal component of Radix Astragali seu Hedysari (Huangqi and exerts potential neuroprotection in experimental ischemic stroke. Here, we systematically assessed the effectiveness and possible mechanisms of AST-IV for experimental acute ischemic stroke. An electronic search in eight databases was conducted from inception to March 2016. The study quality score was evaluated using the CAMARADES. Rev Man 5.0 software was used for data analyses. Thirteen studies with 244 animals were identified. The study quality score of included studies ranged from 3/10 to 8/10. Eleven studies showed significant effects of AST-IV for ameliorating the neurological function score (P<0.05; seven studies for reducing the infarct volume (P<0.05; and three or two studies for reducing the brain water content and Evans blue leakage (P<0.05, respectively, compared with the control. The mechanisms of AST-IV for ischemic stroke are multiple such as antioxidative/nitration stress reaction, anti-inflammatory, and antiapoptosis. In conclusion, the findings of present study indicated that AST-IV could improve neurological deficits and infarct volume and reduce the blood-brain barrier permeability in experimental cerebral ischemia despite some methodological flaws. Thus, AST-IV exerted a possible neuroprotective effect during the cerebral ischemia/reperfusion injury largely through its antioxidant, anti-inflammatory, and antiapoptosis properties.

  10. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-02-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled (/sup 14/C)glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-(1,2-/sup 14/C)choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis.

  11. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    International Nuclear Information System (INIS)

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-01-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [ 14 C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2- 14 C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis

  12. MRI of cerebral ischaemia in rats with occlusion of the middle cerebral artery

    International Nuclear Information System (INIS)

    Thuomas, K.AA.; Kotwica, Z.; Bergstroem, K.; Bolander, H.; Hillered, L.; Olsson, Y.; Ponten, U.; Persson, L.

    1991-01-01

    The development of ischaemic brain oedema caused by middle cerebral artery (MCA) occlusion was studied by serial magnetic resonance imaging (MRI) in rats. Multiple spin echo sequences were used with TR = 1500 ms and TE = 30-240 ms (8 echos). Substraction images were obtained by subtracting the last three echos from the first echo. Fourteen rats were studied 3, 6, and 12 h and 1, 1.5, 3, 4, 6, and 8 days after MCA occlusion, and 2 of them also 3 and 6 weeks later. Two T2 components could be separated, a fast one representing bound water and a slow one representing free bulk water. MR showed T2 prolongation even on the first examination, and the highest values were observed 24 h after occlusion. The subsequent examinations showed a slow reduction in oedema. MR studies 3 and 6 weeks after occlusion revealed an area of very long T2, which correlated well with infarction shown by histology. The substraction images demonstrated both the infarct location and the oedematous changes in the surrounding uninfarcted tissue. MRI imaging employing T2 components and subtraction images appears to be a valuable method for observing the time course of the development and resolution of oedema in cerebral infarction. (orig.)

  13. Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion.

    Science.gov (United States)

    Liu, Yanqun; Tang, Guanghui; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

    2014-09-05

    Current studies demonstrated that metformin is not only a hypoglycemic drug, but also a neuro-protective agent. However, the effect of metformin during ischemic brain injury is unclear. The aim of the present study is to explore the effect of metformin during ischemic brain injury. Adult male CD1 mice underwent 90min transient middle cerebral artery occlusion. Metformin (200mg/kg) was given at the time of reperfusion daily until sacrifice. Results showed that metformin treatment significantly reduced ischemia-induced brain atrophy volume compared to the control (pcerebral artery occlusion, suggesting that metformin is a potential new drug for ischemic stroke therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. The protective effect of dexanabinol (HU-211) on nitric oxide and cysteine protease-mediated neuronal death in focal cerebral ischemia.

    Science.gov (United States)

    Durmaz, Ramazan; Ozden, Hilmi; Kanbak, Güngör; Aral, Erinç; Arslan, Okan Can; Kartkaya, Kazim; Uzuner, Kubilay

    2008-09-01

    We hypothesized that dexanabinol can prevent neuronal death by protecting neuronal lysosomes from nitric oxide (NO)-mediated toxicity, and in turn, by suppressing the release of cathepsins during cerebral ischemia. Focal cerebral ischemia was induced in two sets of animals by permanent middle cerebral artery occlusion. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. In post-ischemic brain tissue, NO content and cathepsin B and L activity increased (p 0.05). The number of eosinophilic and apoptotic neurons increased in the post-ischemic cerebral cortex (p agent for the treatment of stroke patients.

  15. Increased radiosensitivity of cerebral capillaries in neonatal Gunn rats as compared to Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Landolt, R.; Arn, D.

    1979-01-01

    The extent of petechial haemorrhages of the cerebral cortex examined between 14 hours and 4 days after X-irradiation to the head was compared in Sprague-Dawley and homozygous Gunn rats with congenital hyperbilirubinaemia. Animals 1 to 2 days old received single doses of either 250, 500 or 750 rad. By means of a special scoring scale the degree of the damage to the micro vasculature was semi-quantitatively estimated. In both strains a significant difference in effect was obtained between 250 and 500 rad, but not between 500 and 750 rad. The shape of the dose-effect curve in Gunn rats was similar to that of Sprague-Dawley rats, but displaced upwards. In Gunn rats the effect of 250 rad was greater that that of 750 rad in Sprague-Dawley rats. Possible radiosensitizing mechanisms are discussed with reference to the literature and these results. (author)

  16. Effect of growth hormone on glycogenesis in rat cerebral cortical slices

    International Nuclear Information System (INIS)

    Visweswaran, P.; Binod Kumar; Azad, V.S.S.; Brahamchari, A.K.; Singh, S.P.

    1994-01-01

    Incubation of cerebral cortical slices of growth hormone treated diabetic and normal rats with U- 14 C glucose showed a two-fold increase in glycogenesis in diabetic rats. Glucose-6-phosphatase activity was lowered while the activities of phosphoglucomutase and phosphorylase were elevated in the cerebral cortex of diabetic rats treated with growth hormone. However, glycogen synthetase activity was slightly depressed. (author). 13 refs., 2 tabs

  17. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.

    Directory of Open Access Journals (Sweden)

    Shinichiro Teramoto

    Full Text Available Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27 is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27 from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27, which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.

  18. Transplanted Dental Pulp Stem Cells Migrate to Injured Area and Express Neural Markers in a Rat Model of Cerebral Ischemia.

    Science.gov (United States)

    Zhang, Xuemei; Zhou, Yinglian; Li, Hulun; Wang, Rui; Yang, Dan; Li, Bing; Cao, Xiaofang; Fu, Jin

    2018-01-01

    Ischemic stroke is a major cause of disability and mortality worldwide, while effective restorative treatments are limited at present. Stem cell transplantation holds therapeutic potential for ischemic vascular diseases and may provide an opportunity for neural regeneration. Dental pulp stem cells (DPSCs) origin from neural crest and have neuro-ectodermal features including proliferation and multilineage differentiation potentials. The rat model of middle cerebral artery occlusion (MCAO) was used to evaluate whether intravenous administration of DPSCs can reduce infarct size and to estimate the migration and trans-differentiation into neuron-like cells in focal cerebral ischemia models. Brain tissues were collected at 4 weeks following cell transplantation and analyzed with immunofluorescence, immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Intravenously administration of rat-derived DPSCs were found to migrate into the boundary of ischemic areas and expressed neural specific markers, reducing infarct volume and cerebral edema. These results suggest that DPSCs treatment may serve as a potential therapy for clinical stroke patients in the future. © 2018 The Author(s). Published by S. Karger AG, Basel.

  19. Activation-induced resetting of cerebral oxygen and glucose uptake in the rat

    DEFF Research Database (Denmark)

    Madsen, P L; Linde, R; Hasselbalch, S G

    1998-01-01

    In the clinical setting it has been shown that activation will increase cerebral glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon further, this study presents an experimental setup that enables precise determination of the ratio between cerebral uptake of glucose...... and oxygen in the awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio between cerebral uptake rates for oxygen, glucose, and lactate was calculated from cerebral arterial-venous differences. During baseline conditions, rats were kept in a closed box designed to minimize...... interference. During baseline conditions CBF was 1.08 +/- 0.25 mL x g(-1) x minute(-1), and the cerebral oxygen to glucose uptake ratio was 5.5. Activation was induced by opening the sheltering box for 6 minutes. Activation increased CBF to 1.81 mL x g(-1) x minute(-1). During activation cerebral glucose...

  20. Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia.

    Science.gov (United States)

    Moraga, Ana; Pradillo, Jesús M; García-Culebras, Alicia; Palma-Tortosa, Sara; Ballesteros, Ivan; Hernández-Jiménez, Macarena; Moro, María A; Lizasoain, Ignacio

    2015-05-10

    Aging is not just a risk factor of stroke, but it has also been associated with poor recovery. It is known that stroke-induced neurogenesis is reduced but maintained in the aged brain. However, there is no consensus on how neurogenesis is affected after stroke in aged animals. Our objective is to determine the role of aging on the process of neurogenesis after stroke. We have studied neurogenesis by analyzing proliferation, migration, and formation of new neurons, as well as inflammatory parameters, in a model of cerebral ischemia induced by permanent occlusion of the middle cerebral artery in young- (2 to 3 months) and middle-aged mice (13 to 14 months). Aging increased both microglial proliferation, as shown by a higher number of BrdU(+) cells and BrdU/Iba1(+) cells in the ischemic boundary and neutrophil infiltration. Interestingly, aging increased the number of M1 monocytes and N1 neutrophils, consistent with pro-inflammatory phenotypes when compared with the alternative M2 and N2 phenotypes. Aging also inhibited (subventricular zone) SVZ cell proliferation by decreasing both the number of astrocyte-like type-B (prominin-1(+)/epidermal growth factor receptor (EGFR)(+)/nestin(+)/glial fibrillary acidic protein (GFAP)(+) cells) and type-C cells (prominin-1(+)/EGFR(+)/nestin(-)/Mash1(+) cells), and not affecting apoptosis, 1 day after stroke. Aging also inhibited migration of neuroblasts (DCX(+) cells), as indicated by an accumulation of neuroblasts at migratory zones 14 days after injury; consistently, aged mice presented a smaller number of differentiated interneurons (NeuN(+)/BrdU(+) and GAD67(+) cells) in the peri-infarct cortical area 14 days after stroke. Our data confirm that stroke-induced neurogenesis is maintained but reduced in aged animals. Importantly, we now demonstrate that aging not only inhibits proliferation of specific SVZ cell subtypes but also blocks migration of neuroblasts to the damaged area and decreases the number of new interneurons in

  1. Electroacupuncture promotes post-stroke functional recovery via enhancing endogenous neurogenesis in mouse focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Yu Ri Kim

    Full Text Available To investigate the question of whether electroacupuncture (EA promotes functional recovery via enhancement of proliferation and differentiation of neuronal stem cells (NSCs in ischemic stroke, EA stimulation with 2 Hz was applied at bilateral acupoints to Baihui (GV20 and Dazhui (GV14 in middle cerebral artery occlusion (MCAO mice. EA stimulation improved neuromotor function and cognitive ability after ischemic stroke. EA stimulation resulted in an increase in the number of proliferated cells, especially in the subventricular zone (SVZ of the ipsilateral hemisphere. Although a very limited number of NSCs survived and differentiated into neurons or astrocytes, EA treatment resulted in a significant increase in the number of proliferative cells and differentiated cells in the hippocampus and SVZ of the ipsilateral hemisphere compared to MCAO mice. EA stimulation resulted in significantly increased mRNA expression of brain-derived neurotrophic factor (BDNF and vascular endothelial growth factor (VEGF. Protein levels of these factors were confirmed in the ipsilateral hippocampus and SVZ by immunohistochemical and Western blotting analyses. Expression of phosphorylated phosphatidylinositol-3-kinase, BDNF, and VEGF-mediated down-stream were enhanced by EA stimulation in newly formed neuroblasts. These results indicate that EA treatment after ischemic stroke may promote post-stroke functional recovery by enhancement of proliferation and differentiation of NSCs via the BDNF and VEGF signaling pathway.

  2. Task-specific compensation and recovery following focal motor cortex lesion in stressed rats.

    Science.gov (United States)

    Kirkland, Scott W; Smith, Lori K; Metz, Gerlinde A

    2012-03-01

    One reason for the difficulty to develop effective therapies for stroke is that intrinsic factors, such as stress, may critically influence pathological mechanisms and recovery. In cognitive tasks, stress can both exaggerate and alleviate functional loss after focal ischemia in rodents. Using a comprehensive motor assessment in rats, this study examined if chronic stress and corticosterone treatment affect skill recovery and compensation in a task-specific manner. Groups of rats received daily restraint stress or oral corticosterone supplementation for two weeks prior to a focal motor cortex lesion. After lesion, stress and corticosterone treatments continued for three weeks. Motor performance was assessed in two skilled reaching tasks, skilled walking, forelimb inhibition, forelimb asymmetry and open field behavior. The results revealed that persistent stress and elevated corticosterone levels mainly limit motor recovery. Treated animals dropped larger amounts of food in successful reaches and showed exaggerated loss of forelimb inhibition early after lesion. Stress also caused a moderate, but non-significant increase in infarct size. By contrast, stress and corticosterone treatments promoted reaching success and other quantitative measures in the tray reaching task. Comparative analysis revealed that improvements are due to task-specific development of compensatory strategies. These findings suggest that stress and stress hormones may partially facilitate task-specific and adaptive compensatory movement strategies. The observations support the notion that hypothalamic-pituitary-adrenal axis activation may be a key determinant of recovery and motor system plasticity after ischemic stroke.

  3. Inhibition of Cathepsins B Induces Neuroprotection Against Secondary Degeneration in Ipsilateral Substantia Nigra After Focal Cortical Infarction in Adult Male Rats

    Directory of Open Access Journals (Sweden)

    Xialin Zuo

    2018-05-01

    Full Text Available Stroke is the leading cause of adult disability in the world. In general, recovery from stroke is incomplete. Accumulating evidences have shown that focal cerebral infarction leads to dynamic trans-neuronal degeneration in non-ischemic remote brain regions, with the disruption of connections to synapsed neurons sustaining ischemic insults. Previously, we had reported that the ipsilateral striatum, thalamus degenerated in succession after permanent distal branch of middle cerebral artery occlusion (dMCAO in Sprague-Dawley (SD rats and cathepsin (Cath B was activated before these relay degeneration. Here, we investigate the role of CathB in the secondary degeneration of ipsilateral substantia nigra (SN after focal cortical infarction. We further examined whether the inhibition of CathB with L-3-trans-(Propyl-carbamoyloxirane-2-carbonyl-L-isoleucyl-L-proline methyl ester (CA-074Me would attenuate secondary degeneration through enhancing the cortico-striatum-nigral connections and contribute to the neuroprotective effects. Our results demonstrated that secondary degeneration in the ipsilateral SN occurred and CathB was upregulated in the ipsilateral SN after focal cortical infarction. The inhibition of CathB with CA-074Me reduced the neuronal loss and gliosis in the ipsilateral SN. Using biotinylated dextran amine (BDA or pseudorabies virus (PRV 152 as anterograde or retrograde tracer to trace striatum-nigral and cortico-nigral projections pathway, CA-074Me can effectively enhance the cortico-striatum-nigral connections and exert neuroprotection against secondary degeneration in the ipsilateral SN after cortical ischemia. Our study suggests that the lysosomal protease CathB mediates the secondary damage in the ipsilateral SN after dMCAO, thus it can be a promising neuroprotective target for the rehabilitation of stroke patients.

  4. Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans.

    Science.gov (United States)

    Nomura, Sadahiro; Fujii, Masami; Inoue, Takao; He, Yeting; Maruta, Yuichi; Koizumi, Hiroyasu; Suehiro, Eiichi; Imoto, Hirochika; Ishihara, Hideyuki; Oka, Fumiaki; Matsumoto, Mishiya; Owada, Yuji; Yamakawa, Takeshi; Suzuki, Michiyasu

    2014-05-01

    Recently, focal brain cooling (FBC) was proposed as a method for treating refractory epilepsy. However, the precise influence of cooling on the molecular basis of epilepsy has not been elucidated. Thus the aim of this study was to assess the effect of FBC on glutamate (Glu) concentration, cerebral blood flow (CBF), and glucose metabolism in patients with intractable epilepsy. Nine patients underwent FBC at 15°C for 30 min prior to cortical resection (n = 6) or hippocampectomy (n = 3). Measurement of metabolites and CBF, as well as electrocorticography (ECoG), was performed. Epileptic discharge (ED), as observed by ECoG, disappeared in the cooling period and reappeared in the rewarming period. Glu concentrations were high during the precooling period and were reduced to 51.2% during the cooling period (p = 0.025). Glycerol levels showed a similar decrease (p = 0.028). Lactate concentration was high during the precooling period and was reduced during the cooling period (21.3% decrease; p = 0.005). Glucose and pyruvate levels were maintained throughout the procedure. Changes in CBF were parallel to those observed by ECoG. FBC reduced EDs and concentrations of Glu and glycerol. This demonstrates the neuroprotective effect of FBC. Our findings confirm that FBC is a reasonable and optimal treatment option for patients with intractable epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  5. Genetic ablation of soluble tumor necrosis factor with preservation of membrane tumor necrosis factor is associated with neuroprotection after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Madsen, Pernille M; Clausen, Bettina H; Degn, Matilda

    2016-01-01

    Microglia respond to focal cerebral ischemia by increasing their production of the neuromodulatory cytokine tumor necrosis factor, which exists both as membrane-anchored tumor necrosis factor and as cleaved soluble tumor necrosis factor forms. We previously demonstrated that tumor necrosis factor...... reduced infarct volumes at one and five days after stroke. This was associated with improved functional outcome after experimental stroke. No changes were found in the mRNA levels of tumor necrosis factor and tumor necrosis factor-related genes (TNFR1, TNFR2, TACE), pro-inflammatory cytokines (IL-1β, IL-6...... knockout mice display increased lesion volume after focal cerebral ischemia, suggesting that tumor necrosis factor is neuroprotective in experimental stroke. Here, we extend our studies to show that mice with intact membrane-anchored tumor necrosis factor, but no soluble tumor necrosis factor, display...

  6. Ultrastructure of rat cerebral vessels 4 months after gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Iwanowski, L; Ostenda, M

    1975-01-01

    The purpose of this paper was to check the current opinion that one of the late postirradiation changes is early senility (Maxwell, Kruger, 1964). The postirradiation changes of the brain parenchyma are well known from the literature; therefore our investigation is limited to brain capillaries and their closest vicinity. This paper constitutes a fragment of a larger work on the role of connective tissue in the aging brain. Six Wistar male rats of the same brood, about 3 months old, were irradiated over the whole body with gamma rays. Three rats were exposed to a dose of 400 R and three to 800 R. The chosen doses were the lowest and the highest, provoking brain edema but still not lethal. Four months after the exposure the rats were perfused with 4% glutaraldehyde intracardiacly and decapitated. Brain specimens were taken from frontoparietal cortex, lateral ventricle wall, from corpus callosum and griseum pontis. The samples were routinely handled for ultrastructural studies. Observations were performed under electron microscopes showed that the cerebral vessels of both groups of animals were similar.

  7. Pharmacological and molecular comparison of K(ATP) channels in rat basilar and middle cerebral arteries

    DEFF Research Database (Denmark)

    Ploug, Kenneth Beri; Edvinsson, Lars; Olesen, Jes

    2006-01-01

    , we studied the possible involvement of endothelial K(ATP) channels by pressurized arteriography after luminal administration of synthetic K(ATP) channel openers to rat basilar and middle cerebral arteries. Furthermore, we examined the mRNA and protein expression profile of K(ATP) channels to rat...... basilar and middle cerebral arteries using quantitative real-time PCR (Polymerase Chain Reaction) and Western blotting, respectively. In the perfusion system, we found no significant responses after luminal application of three K(ATP) channel openers to rat basilar and middle cerebral arteries...

  8. A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model.

    Science.gov (United States)

    Fujiwara, Norio; Som, Angel T; Pham, Loc-Duyen D; Lee, Brian J; Mandeville, Emiri T; Lo, Eng H; Arai, Ken

    2016-10-28

    A free radical scavenger edaravone is clinically used in Japan for acute stroke, and several basic researches have carefully examined the mechanisms of edaravone's protective effects. However, its actions on pro-inflammatory responses under stroke are still understudied. In this study, we subjected adult male Sprague-Dawley rats to 90-min middle cerebral artery (MCA) occlusion followed by reperfusion. Edaravone was treated twice via tail vein; after MCA occlusion and after reperfusion. As expected, edaravone-treated group showed less infarct volume and edema formation compared with control group at 24-h after an ischemic onset. Furthermore, edaravone reduced the levels of plasma interleukin (IL)-1β and matrix metalloproteinase-9 at 3-h after ischemic onset. Several molecules besides IL-1β and MMP-9 are involved in inflammatory responses under stroke conditions. Therefore, we also examined whether edaravone treatment could decrease a wide range of pro-inflammatory cytokines/chemokines by testing rat plasma samples with a rat cytokine array. MCAO rats showed elevations in plasma levels of CINC-1, Fractalkine, IL-1α, IL-1ra, IL-6, IL-10, IP-10, MIG, MIP-1α, and MIP-3α, and all these increases were reduced by edaravone treatment. These data suggest that free radical scavengers may reduce systemic inflammatory responses under acute stroke conditions, and therefore, oxidative stress can be still a viable target for acute stroke therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Characterization of α2-adrenergic receptors in rat cerebral cortex

    International Nuclear Information System (INIS)

    Nasseri, A.

    1987-01-01

    The properties of 3 H-RX 781094 binding sites and the receptors inhibiting norepinephrine (NE) release and cyclic AMP accumulation in rat cerebral cortex were compared. 3 H-RX 781094, a new α 2 -adrenergic receptor antagonist radioligand, labelled a homogeneous population of binding sites at 37 0 C with the pharmacological specificity expected of α 2 -adrenergic receptors. Gpp(NH)p and NaCl decreased the potencies of agonists at 3 H-RX 781094 binding sites 3-22 fold. Antagonists blocked the inhibition of potassium-evoked tritium release from cortical slices preloaded with 3 H-NE by exogenous NE with potencies similar to those observed in competition for specific 3 H-RX 781094 binding sites. EEDQ, an irreversible α 2 -adrenergic receptors and determine whether there was a receptor reserve for the inhibition of tritium release

  10. Improvement of oxygen supply by an artificial carrier in combination with normobaric oxygenation decreases the volume of tissue hypoxia and tissue damage from transient focal cerebral ischemia

    NARCIS (Netherlands)

    Seiffge, David J.; Lapina, Natalia E.; Tsagogiorgas, Charalambos; Theisinger, Bastian; Henning, Robert H.; Schilling, Lothar

    Tissue hypoxia may play an important role in the development of ischemic brain damage. In the present study we investigated in a rat model of transient focal brain ischemia the neuroprotective effects of increasing the blood oxygen transport capacity by applying a semifluorinated alkane

  11. Anti-inflammatory and neuroprotective effects of sanguinarine following cerebral ischemia in rats

    OpenAIRE

    Wang, Qin; Dai, Peng; Bao, Han; Liang, Ping; Wang, Wei; Xing, An; Sun, Jianbin

    2016-01-01

    Stroke is one of the leading causes of mortality worldwide. Protective agents that can diminish injuries caused by cerebral ischemia-reperfusion (I/R) are important in alleviating the harmful outcomes of stroke. The aim of the present study was to investigate the protective role of sanguinarine in cerebral I/R injury. A rat middle cerebral artery occlusion model was used to assess the clinical effect of sanguinarine, and inflammatory cytokines in the serum were detected by ELISA. Western blot...

  12. Reduction of cerebral injury in stroke-prone spontaneously hypertensive rats by amlodipine

    NARCIS (Netherlands)

    Blezer, E.L.A.; Nicolaij, K.; Goldschmeding, R.C.; Koomans, H.A.; Joles, Jaap

    2002-01-01

    Dihydropyridine Ca2+ channel antagonists, initiated together with high salt intake, prevent the development of hypertension and subsequent cerebral damage in stroke-prone spontaneously hypertensive rats (SHRSP). We hypothesized that the dihydropyridine Ca2+ channel antagonist amlodipine

  13. Microangiographic study of the normal anatomy of the cerebral venous system in rats

    International Nuclear Information System (INIS)

    Schumacher, M.

    1984-01-01

    Microangiographic serial cuts were performed in 20 Sprague-Dawley rats for a systematic study of the normal anatomy of the cerebral veins. The draining pathways of the cerebral and cerebellar cortex, basal ganglia, hypothalamus, hippocampus and the midbrain are described and discussed with regard to their different functions. (orig.)

  14. Protective effect and its mechanism of curcumin on ischemia-reperfusion injury of cerebral cortex in rats

    Directory of Open Access Journals (Sweden)

    Li LIU

    2013-03-01

    Full Text Available Objective  To investigate the effect of curcumin pretreatment on the expression of uncoupling protein 2 (UCP2 and mitochondrial transcription factor A (MTFA in rats' cerebral cortex against focal ischemia reperfusion injury. Methods  Eighty male SD rats weighed 220g–300g were randomly divided into 4 groups: sham-operated group, ischemia/reperfusion (I/R group, curcumine 50mg/kg+I/R (low dose group, and curcumine 100mg/kg+I/R (high dose group. The common carotid artery, external carotid artery and internal carotid artery on the right side were exposed in the sham-operated group. Animals of the other groups were subjected to a 2-hour period of right middle cerebral artery occlusion, followed by 24 hours of reperfusion, and then they were sacrificed. Curcumin was administered (ip in a dose of 50mg/kg (low dose group or 100mg/kg (high dose group for 5 days, respectively, prior to arterial occlusion. The pathological changes in neurons and their mitochondria in the cerebral cortex supplied by middle cerebral artery were observed with Nissl staining and electron microscope, respectively. The expressions of UCP2 and MTFA in corresponding cotex were assessed by immunohistochemistry and RT-PCR. Results  Compared with sham-operated group, animals in I/R group presented edema of neurons in the corresponding cortex, reduction in the number of Nissl bodies, and swelling of mitochondria with broken, even lysis of cristae. Low dose and high dose of curcumin pretreatment before brain ischemia significantly alleviated the loss of neurons and the damage of mitochondria, accompanied with an increase in the expression of UCP2 and TFAM (P<0.05, and the changes appeared a dose-dependent manner (P<0.05. Conclusions  Curcumin may prevent neurons from focal cerebral ischemia reperfusion injury by up-regulating UCP2 and MTFA. Regulation of mitochondrial biogenesis may probably be a potential target of curcumin as a neuroprotective drug.

  15. A Study on the Effect of Neurogenesis and Regulation of GSK3β/PP2A Expression in Acupuncture Treatment of Neural Functional Damage Caused by Focal Ischemia in MCAO Rats

    Directory of Open Access Journals (Sweden)

    Ding Luo

    2014-01-01

    Full Text Available 170 SD rats were randomly divided to five groups. Rats in model group, no-acupuncture group, and acupuncture group were subjected to MCAO surgery. Acupuncture group received 3 consecutive acupuncture treatments at a parameter that deep in 2 mm towards apex nasi and thrust/lifted at 3 times per second for 1 minute, while model group and no-acupuncture group were no-intervention control groups. Serious neural functional damage and sharp decrease of cerebral blood flow, obvious infarction volume, increased nestin mRNA expression, and immunopositive cells population (nestin+, BrdU+ and nestin/BrdU+ were found in MCAO rats which had not been observed in normal group and sham-operated group. However, the damage was attenuated by rat’s “self-healing” capacity 3 days after MCAO. And the “self-healing” capacity can be strengthen by acupuncture treatment through increasing cerebral blood flow, neurogenesis, and regulation of gene transcription or GSK-3β and PP2A expression. In conclusion, the present study indicates that the underlying mechanism of acupuncture treatment on neural functional damage caused by focal ischemia injury is a multiple interaction which may involve improved cerebral blood supply, neurogenesis, and regulation of gene transcription or GSK-3β and PP2A expression in MCAO rats.

  16. Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.

    Science.gov (United States)

    Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

    2014-08-01

    Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.

  17. Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats.

    Science.gov (United States)

    Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G

    2013-05-01

    Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect.

  18. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

  19. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    International Nuclear Information System (INIS)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-01-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased

  20. Neuroprotective effect of p-coumaric acid in rat model of embolic cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Mustafa Guven

    2015-04-01

    Conclusion:Our results showed that p-coumaric acid is a neuroprotective agent on account of its strong anti-oxidant and anti-apoptotic features. Moreover, p-coumaric acid decreased the focal ischemia. Extra effort should be made to introduce p-coumaric acid as a promising therapeutic agent to be utilized for treatment of human cerebral ischemia in the future.

  1. The pre-ischaemic neuroprotective effects of N1-dansyl-spermine in a transient focal cerebral ischaemia model in mice.

    Science.gov (United States)

    Li, Jun; Henman, Martin C; Tatlisumak, Turgut; Shaw, Graham G; Doyle, Karen M

    2005-09-07

    The pre-ischaemic neuroprotective potential of a novel polyamine/NMDA antagonist N1-dansyl-spermine (1-5 mg kg(-1)) was studied in a transient focal cerebral ischaemia model in mice in comparison to a reference compound, MK-801 (1 or 3 mg kg(-1)). The intraluminal suture transient middle cerebral artery occlusion (MCAO) model was used. N1-dansyl-spermine and MK-801 were administered (i.p.) 30 min prior to ischaemia. A range of histological and behavioural assessments was employed. N1-dansyl-spermine had a comparable effect to MK-801 at reducing the percentage hemisphere lesion volume (%HLV) at the doses tested. Furthermore, N1-dansyl-spermine reduced the ischaemic brain oedema, which MK-801 did not. N1-dansyl-spermine significantly reversed the decrease of locomotor activity (LMA) caused by the MCAO and showed a significant effect at improving the rotarod performance impaired by MCAO. In contrast, MK-801 had no beneficial effect on sensorimotor function and even worsened the LMA. These results clearly demonstrate the pre-ischaemic neuroprotective effect of N1-dansyl-spermine in a transient focal cerebral ischaemia model.

  2. Effects of Mercury Chloride on the Cerebral Cortex of Adult Wistar Rats

    African Journals Online (AJOL)

    Mercury is among the heavy metals that have been reported to cause devastating health problem worldwide. The primary site of action of mercury chloride is the central nervous system. This study investigated the effect of mercury chloride on the cerebral cortex of adult wistar rats. Twenty-four (24) adult wistar rats were used ...

  3. Electroacupuncture ameliorates post-stroke learning and memory through minimizing ultrastructural brain damage and inhibiting the expression of MMP-2 and MMP-9 in cerebral ischemia-reperfusion injured rats.

    Science.gov (United States)

    Lin, Ruhui; Yu, Kunqiang; Li, Xiaojie; Tao, Jing; Lin, Yukun; Zhao, Congkuai; Li, Chunyan; Chen, Li-Dian

    2016-07-01

    The aim of the present study was to investigate the potential neuroprotective effects of electroacupuncture (EA) in the treatment of cerebral ischemia/reperfusion (I/R) injury, and to elucidate the association between this neuroprotective effect and brain ultrastructure and expression of matrix metalloproteinase (MMP)‑2 and 9. Rats underwent focal cerebral I/R injury by arterial ligation and received in vivo therapeutic EA at the Baihui (DU20) and Shenting (DU24) acupoints. The therapeutic efficacy was then evaluated following the surgery. The results of the current study demonstrated that EA treatment significantly ameliorated neurological deficits and reduced cerebral infarct volume compared with I/R injured rats. Furthermore, EA improved the learning and memory ability of rats following I/R injury, inhibited blood brain barrier breakdown and reduced neuronal damage in the ischemic penumbra. Furthermore, EA attenuated ultrastructural changes in the brain tissue following ischemia and inhibited MMP‑2/MMP‑9 expression in cerebral I/R injured rats. The results suggest that EA ameliorates anatomical deterioration, and learning and memory deficits in rats with cerebral I/R injury.

  4. Comparative studies of D2 receptors and cerebral blood flow in hemi-Parkinsonism rats

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    2000-01-01

    Objective: To study the relationship between dopamine D 2 receptors and cerebral blood flow in hemi-Parkinsonism rats. Methods: Hemi-Parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat to rotate toward the intact side was used to select the rat models, 125 I-IBZM in vivo autoradiography and 99 Tc m -HMPAO regional cerebral biodistribution analysis were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD was used to measure striatum DA and its metabolite content . Results: the lesioned side striatum DA and its metabolites homovanillic acid (HVA) 3,4-dihyroxy-phenylacetic acid (DOPAC) reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-Parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (P 0.05). Conclusions: the 6-OH-DA lesioned side DA content decreased significantly and thus induced a compensative up-regulation of striatum D 2 receptor binding sites in hemi-Parkinsonism rats, which show good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-Parkinsonism

  5. Preliminary EEG study of protective effects of Tebonin in transient global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Zagrean, L; Vatasescu, R; Munteanu, A M

    2000-01-01

    and metabolism. The objective of this study was to investigate the effects of preventive treatment with Ginkgo biloba extract (EGb 761--Tebonin) in cerebral global ischemia and reperfusion in rats using computerized EEG analysis. Ginkgo biloba extract, known to be, in vitro, a free radicals scavanger and a PAF......--antagonist, was administrated in dose of 100 mg/kg over 24 hours, for 5 days before and 5 days after cerebral ischemia--reperfusion. The apparition of isoelectric EEG (flat-line) following 4-vessel occlusion was observed after a mean time of 25 sec. in Ginkgo biloba treated rats and after 18 sec. in control rats (p

  6. Distribution of catecholamines and serotonin in the rat cerebral cortex:

    International Nuclear Information System (INIS)

    Reader, T.A.

    1981-01-01

    The rat cerebral cortex was dissected in five regions and analyzed for the catecholamines noradrenaline, adrenaline and dopamine, and for the indoleamine seroton in using sensitive radioenzymatic assay methods with thin-layer-chromatography. The noradrenaline concentration was highest in the ventral cortex, lateral to the hypothalamus, had intermediate values for the prefrontal, frontal and parietal cortical areas and was lowest in the occipital cortex. Dopamine levels were also highest in the cortex lateral to the hypothalamus, and moderate in the prefrontal and frontal cortical areas, with the lowest values measured for the occipital cortex. The ratios dopamine/noradrenaline further support the hypothesis that they are independent transmitters. Traces of adrenaline were measured in all regions examined. The serotonin distribution was found to be non-homogeneous, with the highest values for the prefrontal cortex and ventral cortex lateral to the hypothalamus. The functional significance of these amines and their ratios are discussed in relation to their role as putative modulators of cortical neuronal excitability. (author)

  7. Effect of electroacupuncture on TRPM7 mRNA expression after cerebral ischemia/reperfusion in rats via TrkA pathway.

    Science.gov (United States)

    Zhao, Li; Shi, Jing; Sun, Ning; Tian, Shunlian; Meng, Xianfang; Liu, Xiaochun; Li, Lingli

    2005-01-01

    The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion), AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGFs effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (PPM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.

  8. Protein metabolism in the rat cerebral cortex in vivo and in vitro as affected by the acquisition enhancing drug piracetam

    NARCIS (Netherlands)

    Nickolson, V.J.; Wolthuis, O.L.

    1976-01-01

    The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but

  9. Long-term evolution of cerebral hemodynamics after brain irradiation in the rat

    International Nuclear Information System (INIS)

    Keyeux, A.; Ochrymowicz-Bemelmans, D.

    1985-01-01

    Long-term evolution of radioisotope indices, evaluating respectively the cerebral blood flow (CBF), the cerebral blood volume (CBV) and the cephalic specific distribution space of iodoantipyrine (ΔIAP) of rat, was studied after brain irradiation at 20 Gy. Radioinduced hemodynamic alterations evidenced by this approach are biphasic and support the prominent role of circulation impairment in the genesis of delayed brain radionecrosis [fr

  10. Anti-inflammatory and neuroprotective effects of sanguinarine following cerebral ischemia in rats.

    Science.gov (United States)

    Wang, Qin; Dai, Peng; Bao, Han; Liang, Ping; Wang, Wei; Xing, An; Sun, Jianbin

    2017-01-01

    Stroke is one of the leading causes of mortality worldwide. Protective agents that can diminish injuries caused by cerebral ischemia-reperfusion (I/R) are important in alleviating the harmful outcomes of stroke. The aim of the present study was to investigate the protective role of sanguinarine in cerebral I/R injury. A rat middle cerebral artery occlusion model was used to assess the clinical effect of sanguinarine, and inflammatory cytokines in the serum were detected by ELISA. Western blotting was performed to examine the change in levels of apoptosis-associated proteins in the injured brains. The results suggested that sanguinarine, an anti-inflammatory agent derived from the roots of Sanguinaria canadensis , improved the state of cerebral ischemia in a rat model. The data demonstrated that when rats were treated with sanguinarine prior to middle cerebral artery occlusion, the infarct volume was reduced significantly. The inflammatory factors tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were measured in sanguinarine and vehicle-treated groups using an enzyme-linked immunosorbent assay, and the expression levels of the three factors were significantly reduced following treatment with sanguinarine (Pprotective effect in cerebral ischemia, and that this effect is associated with the anti-inflammatory and anti-apoptotic properties of sanguinarine.

  11. Characterization of beta-adrenergic receptors in synaptic membranes from rat cerebral cortex and cerebellum

    International Nuclear Information System (INIS)

    Lautens, L.

    1986-01-01

    Beta-adrenergic receptor ligand binding sites have been characterized in synaptic membranes from rat cerebral cortex and cerebellum using radioligand binding techniques. The equilibrium and kinetic properties of binding were assessed. The binding sites were non-interacting and exhibited two states of agonist binding which were sensitive to guanyl nucleotide. Synaptic membranes from cerebral cortex contained an equal number of beta 1 - and beta 2 -receptors; membranes from cerebellum possessed more beta 2 -than beta 1 -receptors. Photoaffinity labeling experiments revealed two different beta-adrenergic receptor polypeptides, R 1 and R 2 (and possibly a third, R 3 ) in synaptic membranes. The ratios of incorporation of photoaffinity label into R 1 : 2 were approximately 1:1 (cerebral cortex) and 5:1 (cerebellum). Photoaffinity labeling of R 1 and R 2 was inhibited equally well by both agonist and antagonist in synaptic membranes from cerebellum; whereas agonist was a less potent inhibitor in membranes from cerebral cortex. Both subtypes of beta-adrenergic receptors exhibited the same apparent molecular weight in synaptic membranes from cerebral cortex. The beta-adrenergic receptors in synaptic membranes from cerebral cortex and cerebellum were glycoproteins which exhibited the same apparent molecular weight after exposure to endoglycosidase F. The partial proteolytic digest maps of photoaffinity labeled beta-adrenergic receptors from rat cerebral cortex, cerebellum, lung and heart were compared

  12. Synchrotron radiation x-ray fluorescence (SRXRF) elemental distribution analysis of brain tissue in a rat model of transient focal ischemia

    International Nuclear Information System (INIS)

    Wang Xuxia; He Rui; Qian Junchao; Lei Hao; Liu Nianqing; Huang Yuying; He Wei

    2005-01-01

    It is shown recently that transient focal ischemia with a duration of 15 minutes in rat leads to delayed neurodegeneration in striatum, as evidenced by shortened T 1 relaxation time in this brain region. The mechanism underlying such T 1 change has been proposed to be deposition of paramagnetic metal ions, such as manganese, in the ischemic brain tissue. To further investigate the characteristics of metal ion deposition in the ischemic brain tissue, elemental (i.e., Ca, Mn, Fe and Zn) distribution was measured in rat brain sections 2 weeks after a 15-min middle cerebral artery occlusion (MCAO) using synchrotron radiation X-Ray fluorescence analysis (SRXRF). The right middle cerebral arteries of 4 Wistar rats weighting 200-250 g were occluded under mild anesthesia (1-1.5% isoflurane) for 15 minutes by inserting a silicon-coated nylon thread from the external carotid artery into the internal carotid artery. Two weeks later the rats were decapitated and the brain was immediately removed, frozen in liquid nitrogen, cut into 100 m sections at the level of striatum with a microtome, and put onto polycarbonate films specially designed for SRXRF examination. All SRXRF spectra obtained with a beam spot size of 100 m x 100 m were normalized to the acquisition time and the counting of the ion chambers, and the contribution from the supporting polycarbonate film was subtracted. The X-ray peak area for each element (A) and the Compton scattering intensity (B) for the whole brain section were obtained. The relative content for each element was taken as the ratio of A to B. The results show that, compared to those in the contralateral striatum (i.e., left hemisphere), the relative contents of Ca and Mn in the ipsilateral striatum (i.e., right hemisphere) increased 1300.3±500.3% and 39±23%, respectively. The relative contents of Fe and Zn in the ischemic striatum showed no obvious changes as compared to control, contrasted to the results reported by Danielisova et al who showed

  13. The pre-ischaemic neuroprotective effect of a novel polyamine antagonist, N1-dansyl-spermine in a permanent focal cerebral ischaemia model in mice.

    Science.gov (United States)

    Li, Jun; Henman, Martin C; Doyle, Karen M; Strbian, Daniel; Kirby, Brian P; Tatlisumak, Turgut; Shaw, Graham G

    2004-12-10

    The polyamine sites on the NMDA receptor complex offer a therapeutic target for focal ischaemia, potentially devoid of most side effects associated with NMDA antagonists. In this study, we investigated the effect of a novel polyamine antagonist, N(1)-dansyl-spermine (0.5-10 mg kg(-1)) in a permanent focal cerebral ischaemia model in mice, and compared its effect to that of MK-801 (0.3-3 mg kg(-1)) following administration 30 min prior to ischaemia. A battery of histological and behavioural tests was employed following permanent middle cerebral artery occlusion to assess any neuroprotective effect. Following middle cerebral artery occlusion, N(1)-dansyl-spermine (1-5 mg kg(-1)) and MK-801 (1 or 3 mg kg(-1)) caused a comparable and significant reduction in the percentage hemisphere lesion volume. Similarly, both drugs significantly reduced oedema and neurological deficit score to a similar extent. Locomotor activity in MCAO mice was not significantly improved by MK-801 or N(1)-dansyl-spermine, although N(1)-dansyl-spermine induced a trend towards significant improvement. Significant improvement in rotarod performance was observed at neuroprotective doses with both drugs. Upon comparison of the profile of effects, N(1)-dansyl-spermine at least matched the effectiveness of MK-801 as a neuroprotective agent in this model. In addition, in sham-operated control mice, N(1)-dansyl-spermine was well tolerated, in contrast to the pronounced adverse effects of MK-801 on locomotor activity and rotarod performance. In conclusion, this study has shown that N(1)-dansyl-spermine is as effective a neuroprotective drug as MK-801 in this model. Moreover, in contrast to MK-801, N(1)-dansyl-spermine could be a promising therapeutic candidate for stroke as it is well tolerated at neuroprotective doses in sham-operated animals.

  14. Effects of the combined treatment of bone marrow stromal cells with mild exercise and thyroid hormone on brain damage and apoptosis in a mouse focal cerebral ischemia model.

    Science.gov (United States)

    Akhoundzadeh, Kobar; Vakili, Abedin; Sameni, Hamid Reza; Vafaei, Abbas Ali; Rashidy-Pour, Ali; Safari, Manouchehr; Mohammadkhani, Razieh

    2017-08-01

    This study examined whether post-stroke bone marrow stromal cells (BMSCs) therapy combined with exercise (EX) and/or thyroid hormone (TH) could reduce brain damage in an experimental ischemic stroke in mice. Focal cerebral ischemia was induced under Laser Doppler Flowmetry (LDF) guide by 45 min of middle cerebral artery occlusion (MCAO), followed by 7 days of reperfusion in albino mice. BMSCs were injected into the right cerebral ventricle 24 h after MCAO, followed by daily injection of T3 (20 μg/100 g weight S.C) and 6 days of running on a treadmill. Infarct size, neurobehavioral test, TUNEL and BrdU positive cells were evaluated at 7 days after MCAO. Treatment with BMSCs and mild EX alone significantly reduced the infarct volume by 23% and 44%, respectively (both, p cells (a marker of apoptosis) was significantly reduced in the EX, BMSCs, BMSCs + EX, BMSCs + TH, and BMSCs + EX + TH groups (all, p cells in the subventricular zone (SVZ) (p cells and the attenuation of apoptosis in ischemia stroke in young mice.

  15. Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Wang, Ai-Hong; Ma, Qian; Wang, Xin; Xu, Gui-Hua

    2018-02-01

    Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke.

  16. Morphologic changes of cerebral veins in hypertensive rats: venous collagenosis is associated with hypertension.

    Science.gov (United States)

    Zhou, Min; Mao, Lijuan; Wang, Ying; Wang, Qian; Yang, Zhiyun; Li, Shurong; Li, Ling

    2015-03-01

    The aims of this study were to determine whether arterial hypertension could affect the venous system of brain and to find out the consequent pathologic changes of cerebral veins. Thirty male Sprague-Dawley rats were divided into 2 groups: a sham-clipped group and a stroke-prone renovascular hypertensive rat group. A 2-kidney 2-clip rat model was used to induce renovascular hypertension in the hypertensive group. Systolic blood pressure was measured by tail cuff once each week. Susceptibility-weighted imaging (SWI) was performed at 12, 16, and 20 weeks after surgery. All the rats were sacrificed after the SWI examination at 20 weeks after surgery. The brains were extracted and embedded in paraffin for histologic examination. Masson trichrome staining was performed to identify venous collagenosis. The sham group demonstrated less prominence of cerebral veins compared with hypertensive groups (P veins on SWI as a sign of venous hypertension and the thickened cerebral venous walls (venous collagenosis), which may play a role in cerebral ischemia and/or infarction, are both consequences of long-term hypertension in hypertensive rats. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  17. Point application with Angong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Dong-shu Zhang

    2015-01-01

    Full Text Available Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar, we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg were administered to the Dazhui (DU14, Qihai (RN6 and Mingmen (DU4 of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14, Qihai (RN6 and Mingmen (DU4. Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.

  18. PTH prevents the adverse effects of focal radiation on bone architecture in young rats.

    Science.gov (United States)

    Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A; Altman, Allison R; Cengel, Keith A; Liu, X Sherry; Qin, Ling

    2013-08-01

    Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Imaging of rat cerebral ischemia-reperfusion injury using99mTc-labeled duramycin

    International Nuclear Information System (INIS)

    Zhang Yuqing; Stevenson, Gail D.; Barber, Christy; Furenlid, Lars R.; Barrett, Harrison H.; Woolfenden, James M.; Zhao Ming; Liu Zhonglin

    2013-01-01

    Objectives: Prompt identification of necrosis and apoptosis in the infarct core and penumbra region is critical in acute stroke for delineating the underlying ischemic/reperfusion molecular pathologic events and defining therapeutic alternatives. The objective of this study was to investigate the capability of 99m Tc-labeled duramycin in detecting ischemia-reperfusion injury in rat brain after middle cerebral artery (MCA) occlusion. Methods: Ischemic cerebral injury was induced in ten rats by vascular insertion of a nylon suture in the left MCA for 3 hr followed by 21–24 hr reperfusion. After i.v. injection of 99m Tc-duramycin (1.0-3.5 mCi), dynamic cerebral images were acquired for 1 hr in six rats using a small-animal SPECT imager. Four other rats were imaged at 2 hr post-injection. Ex vivo images were obtained by autoradiography after sacrifice. Histologic analyses were performed to assess cerebral infarction and apoptosis. Results: SPECT images showed that 99m Tc-duramycin uptake in the left cerebral hemisphere was significantly higher than that in the right at 1 and 2 hr post-injection. The level of radioactive uptake in the ischemic brain varied based on ischemic severity. The average ratio of left cerebral hot-spot uptake to right hemisphere radioactivity, as determined by computerized ROI analysis, was 4.92 ± 0.79. Fractional washout at 1 hr was 38.2 ± 4.5% of peak activity for left cerebral hot-spot areas and 80.9 ± 2.0% for remote control areas (P 99m Tc-duramycin SPECT imaging may be useful for detecting and quantifying ongoing apoptotic neuronal cell loss induced by ischemia-reperfusion injury.

  20. Effects of Mild Blast Traumatic Brain Injury on Cerebral Vascular, Histopathological, and Behavioral Outcomes in Rats

    Science.gov (United States)

    Zeng, Yaping; Deyo, Donald; Parsley, Margaret A.; Hawkins, Bridget E.; Prough, Donald S.; DeWitt, Douglas S.

    2018-01-01

    Abstract To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry [LDF]), and mean arterial blood pressure (MAP) cerebral vascular resistance were measured for 2 h post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. Neuronal injury was assessed (Fluoro-Jade C [FJC]) 24 and 48 h post-bTBI. Neurological outcomes (beam balance and walking tests) and working memory (Morris water maze [MWM]) were assessed 2 weeks post-bTBI. Because impact TBI (i.e., non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function in part because of the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO−), the effects of the administration of the ONOO− scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for 2 h post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and in the numbers of FJC-positive cells in the brain, and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend toward increased cerebral perfusion, suggesting that ONOO− may contribute to blast-induced cerebral vascular dysfunction. PMID:29160141

  1. Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

    OpenAIRE

    Najmeh Kabiri; Mahbubeh Setorki

    2016-01-01

    The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99). Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly hi...

  2. Asymmetry in the brain influenced the neurological deficits and infarction volume following the middle cerebral artery occlusion in rats

    OpenAIRE

    Zhang Meizeng; Gao Huanmin

    2008-01-01

    Abstract Background Paw preference in rats is similar to human handedness, which may result from dominant hemisphere of rat brain. However, given that lateralization is the uniqueness of the humans, many researchers neglect the differences between the left and right hemispheres when selecting the middle cerebral artery occlusion (MCAO) in rats. The aim of this study was to evaluate the effect of ischemia in the dominant hemisphere on neurobehavioral function and on the cerebral infarction vol...

  3. Focal ischaemia caused by instability of cerebrovascular tone during attacks of hemiplegic migraine. A regional cerebral blood flow study

    DEFF Research Database (Denmark)

    Friberg, L; Olsen, T S; Roland, P E

    1987-01-01

    During the course of hemiplegic migraine in 3 patients, changes in regional cerebral blood flow (rCBF) were recorded by the intracarotid 133Xe method and a 254 multidetector camera covering one hemisphere. The rCBF measurements were performed in conjunction with cerebral angiography. During...... the patients developed transient motor and/or sensory deficits and subsequently severe headache. No signs of arterial occlusion were found. In the over and underperfused regions blood flow fluctuated rapidly because of instability of cerebrovascular tone, defined as transient constriction of the smallest...

  4. VIP/PACAP receptors in cerebral arteries of rat

    DEFF Research Database (Denmark)

    Erdling, André; Sheykhzade, Majid; Maddahi, Aida

    2013-01-01

    BACKGROUND: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP)-containing nerves surround cerebral blood vessels. The peptides have potent vasodilator properties via smooth muscle cell receptors and activation of adenylate cyclase. The purpose of this s......BACKGROUND: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP)-containing nerves surround cerebral blood vessels. The peptides have potent vasodilator properties via smooth muscle cell receptors and activation of adenylate cyclase. The purpose...

  5. Comparative studies of D2 receptors and cerebral blood flow in hemi-parkinsonism rats

    International Nuclear Information System (INIS)

    Lin, Y.; Lin, X.

    2000-01-01

    To study the relationship between dopamine (DA) D 2 receptors and cerebral blood flow in hemiparkinsonism rats. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat rotates toward the intact side was used to screen that rats, 125 I-IBZM in vivo autoradiography and 99m Tc-HM-PAO regional brain biodistribution were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD were used to measure the concentration of DA and it metabolites homovanillic acid (HVA), 3,4-dehydroxyphenyl acetic acid (DOPAC) in bilateral striatum (ST). The lesioned side ST DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and pseudo-operated control group, ST/cerebellum (CB) 125 I-IBZM uptake ratio was 8.04 ±0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (p 99m Tc 30.1±4.53% enhancement as compared to the intact side, and also show good correlation with 30 min Apo induced rotation numbers (r=0.98), the regional cerebral blood flow study didn't show significant difference between bilateral brain cortex area (p>0.05). The DA content decreased significantly and induced an up-regulation of ST D 2 receptor binding sites in 6-OH-DA lesioned side in hemi-parkinsonism rats, the increased percentage of lesioned-intact side ST/CB 125 I-IBZM uptake ratio showed good correlation with rotation behavior induced by Apo. Compare with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-parkinsonism

  6. Radial extracorporeal shock wave therapy improves cerebral blood flow and neurological function in a rat model of cerebral ischemia.

    Science.gov (United States)

    Kang, Nan; Zhang, Jing; Yu, Xiaotong; Ma, Yuewen

    2017-01-01

    We performed middle cerebral artery occlusion (MCAO) in rats to investigate the effect and some of the underlying mechanisms of radial extracorporeal shock wave therapy (rESWT) in cerebral ischemia rats. We measured neurological function and cerebral blood flow (CBF) using a full-field laser perfusion imager and brain infarct volume on days 3, 12, and 30. Immunofluorescence, western blot, and real-time polymerase chain reaction (PCR) techniques were used to detect the expression of vascular endothelial growth factor (VEGF), neuron-specific enolase (NSE), nestin, Wnt3a, and β-catenin in the ischemic hemisphere. The dose of rESWT used on the head revealed remarkable advantages over sham rESWT, as demonstrated by improved neurological function scores, increased CBF, and reduced brain infarct volume. Furthermore, applying rESWT to the head and limbs enhanced short-term neurological function. Our results confirmed that rESWT can induce VEGF expression over an extended period with a profound effect, which may be the primary reason for CBF recovery. High NSE and nestin expression levels suggest that rESWT enhanced the number of neurons and neural stem cells (NSCs). Wnt3a and β-catenin expression were up-regulated in the ischemic hemisphere, indicating that rESWT promoted NSC proliferation and differentiation via the Wnt/β-catenin pathway. Overall, our findings suggest that an appropriate rESWT dose delivered to the head of rats helps restore neurological function and CBF, and additional application of rESWT to the limbs is more effective than treating the head alone.

  7. Effects of electroacupuncture on the cortical extracellular signal regulated kinase pathway in rats with cerebral ischaemia/reperfusion.

    Science.gov (United States)

    Wu, Chunxiao; Li, Chun; Zhou, Guoping; Yang, Lu; Jiang, Guimei; Chen, Jing; Li, Qiushi; Zhan, Zhulian; Xu, Xiuhong; Zhang, Xin

    2017-12-01

    To explore the effects of electroacupuncture (EA) on the phosphorylated extracellular signal regulated kinase (p-ERK) pathway of the cerebral cortex in a rat model of focal cerebral ischaemia/reperfusion (I/R). 160 adult Sprague-Dawley rats underwent middle carotid artery occlusion (MCAO) to establish I/R injury and were randomly divided into four groups (n=40 each) that remained untreated (I/R group) or received EA at LU5, LI4, ST36 and SP6 (I/R+EA group), the ERK inhibitor PD98059 (I/R+PD group), or both interventions (I/R+PD+EA groups). An additional 40 rats undergoing sham surgery formed a healthy control group. Eight rats from each group were sacrificed at the following time points: 2 hours, 6 hours, 1 day, 3 days and 1 week. Neurological function was assessed using neurological deficit scores, morphological examination was performed following haematoxylin-eosin staining of cortical tissues, and apoptotic indices were calculated after terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labelling. Cortical protein and mRNA expression of p-ERK and ERK were measured by immunohistochemistry and real-time quantitative PCR, respectively. Compared with the I/R group, neurological deficit scores and apoptotic indices were lower in the I/R+EA group at 1 and 3 days, whereas mRNA/protein expression of ERK/p-ERK was higher in the EA group at all time points studied. Our results suggest that EA can alleviate neurological deficits and reduce cortical apoptosis in rats with I/R injury. These anti-apoptotic effects may be due to upregulation of p-ERK. Moreover, apoptosis appeared to peak at 1 day after I/R injury, which might therefore represent the optimal time point for targeting of EA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. THE FATE OF MDACH1-EXPRESSING CELLS IN THE DORSAL PART OF THE LATERAL VENTRICLES FOLLOWING FOCAL CEREBRAL ISCHEMIA

    Czech Academy of Sciences Publication Activity Database

    Anděrová, Miroslava; Pivoňková, Helena; Honsa, Pavel

    2013-01-01

    Roč. 61, Supplement 1 (2013), S125-S126 ISSN 0894-1491. [European Meeting on Glia l Cell Function in Health and Disease /11./. 03.07.2013-06.07.2013, Berlin] Institutional support: RVO:68378041 Keywords : cerebral ischemia * neuroscience * MDACH1 Subject RIV: FH - Neurology

  9. Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats.

    Science.gov (United States)

    Feng, Xiaodong; Yang, Shanli; Liu, Jiao; Huang, Jia; Peng, Jun; Lin, Jiumao; Tao, Jing; Chen, Lidian

    2013-05-01

    Cognitive impairment is a serious mental deficit following stroke that severely affects the quality of life of stroke survivors. Nuclear factor‑κB (NF-κB)-mediated neuronal cell apoptosis is involved in the development of post-stroke cognitive impairment; therefore, it has become a promising target for the treatment of impaired cognition. Acupuncture at the Baihui (DU20) and Shenting (DU24) acupoints is commonly used in China to clinically treat post‑stroke cognitive impairment; however, the precise mechanism of its action is largely unknown. In the present study, we evaluated the therapeutic efficacy of electroacupuncture against post-stroke cognitive impairment and investigated the underlying molecular mechanisms using a rat model of focal cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture at Baihui and Shenting was identified to significantly ameliorate neurological deficits and reduce cerebral infarct volume. Additionally, electroacupuncture improved learning and memory ability in cerebral I/R injured rats, demonstrating its therapeutic efficacy against post-stroke cognitive impairment. Furthermore, electroacupuncture significantly suppressed the I/R-induced activation of NF-κB signaling in ischemic cerebral tissues. The inhibitory effect of electroacupuncture on NF-κB activation led to the inhibition of cerebral cell apoptosis. Finally, electroacupuncture markedly downregulated the expression of pro-apoptotic Bax and Fas, two critical downstream target genes of the NF-κB pathway. Collectively, our findings suggest that inhibition of NF-κB‑mediated neuronal cell apoptosis may be one mechanism via which electroacupuncture at Baihui and Shenting exerts a therapeutic effect on post-stroke cognitive impairment.

  10. Higher density of serotonin-1A receptors in the hippocampus and cerebral cortex of alcohol-preferring P rats

    International Nuclear Information System (INIS)

    Wong, D.T.; Threlkeld, P.G.; Lumeng, L.; Li, Ting-Kai

    1990-01-01

    Saturable [ 3 H]-80HDPAT binding to 5HT-1A receptors in membranes prepared from hippocampus and frontal cerebral cortex of alcohol-preferring (P) rats and of alcohol-nonpreferring (NP) rats has been compared. The B max values or densities of recognition sites for 5HT-1A receptors in both brain areas of the P rats are 38 and 44 percent lower in the P rats than in the NP rats. The corresponding K D values are 38 and 44 percent lower in the P rats than in the NP rats, indicating higher affinities of the recognition sites for the 5HT-1A receptors in hippocampus and cerebral cortex of the P rats. These findings indicate either an enrichment of 5HT-1A receptor density during selective breeding for alcohol preference or an upregulation of 5HT-1A receptors of 5HT found in these brain areas of P rats as compared with the NP rats

  11. Co-60 and Ca-45 autoradiography in cerebral ischemia in the rat

    NARCIS (Netherlands)

    Stevens, H; Krop-van Gastel, W; Korf, J

    1998-01-01

    Radioisotopes of divalent Co (Co-57 in Single photon emission tomography (SPECT)and Co-55 in positron emission tomography (PET) have clinically been applied to visualize Ca related brain damage. The cerebral uptake of Ca-45 and Co-60 in a unilateral stroke model in the rat was compared; 100 mu Ci

  12. CRYOPRESERVATION OF FRESHLY ISOLATED SYNAPTOSOMES PREPARED FROM THE CEREBRAL-CORTEX OF RATS

    NARCIS (Netherlands)

    GLEITZ, J; BEILE, A; WILFFERT, B; TEGTMEIER, F

    In the present study, we established a cryopreservation method for freshly isolated synaptosomes prepared from the cerebral cortex of rats. Freshly prepared synaptosomes were either shock-frozen or frozen under temperature-controlled conditions using a programmable temperature controller. Each group

  13. Proteinuria precedes cerebral edema in stroke-prone rats : a magnetic resonance imaging study

    NARCIS (Netherlands)

    Blezer, E.L.A.; Schurink, M.; Nicolaij, K.; Dop Bär, P.R.; Jansen, G.H.; Koomans, H.A.; Joles, Jaap

    1998-01-01

    Background and Purpose: Stroke-prone spontaneously hypertensive rats (SHRSP) subjected to high sodium intake develop severe hypertension, cerebral edema, and proteinuria, culminating in organ damage and early death. MRI, which can be applied serially, provides the unique opportunity to study

  14. Gene expression and molecular changes in cerebral arteries following subarachnoid hemorrhage in the rat

    DEFF Research Database (Denmark)

    Vikman, Petter; Beg, Saema; Khurana, Tejvir S

    2006-01-01

    OBJECT: The authors investigated early changes in the cerebral arteries of rats that occur after subarachnoid hemorrhage (SAH). METHODS: Messenger RNA was investigated by performing microarray and quantitative real-time polymerase chain reaction (PCR) analyses, and protein expression was shown...

  15. Brain scan in cerebral ischemia. An experimental model in the rat

    International Nuclear Information System (INIS)

    Turner, J.H.

    1975-01-01

    A rapid embolic method for consistent induction of stroke in the rat is described. Brain scans were performed using a micro-pinhole collimator system, and the value of the model for studies in localization of radiopharmaceuticals in cerebral ischemia is demonstrated

  16. Nimodipine Effects on Cerebral Microvessels and Sciatic Nerve in Aging Rats

    NARCIS (Netherlands)

    de Jong, Giena; Jansen, Arthur; Horvath, E.; Gispen, W.H.; Luiten, P.G.M.

    1992-01-01

    At the ultrastructural level different anomalies of the cerebral microvasculature were encountered in the brains of aged rats. These aberrations can either be attributed to degeneration processes or to the perivascular deposition of, e.g., collagen fibrils and other, unidentified, proteinous debris.

  17. Silymarin improves the behavioural, biochemical and histoarchitecture alterations in focal ischemic rats: a comparative evaluation with piracetam and protocatachuic acid.

    Science.gov (United States)

    Muley, Milind M; Thakare, Vishnu N; Patil, Rajesh R; Kshirsagar, Ajay D; Naik, Suresh R

    2012-08-01

    Comparative neuroprotective potential of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) was evaluated in focal ischemic rats. Various pharmacological, biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite content, brain water content) and behavioural (memory impairment, motor control, neurological score) including infarct size and histopathological alterations were evaluated. Silymarin (200mg/kg) and PCA treatment significantly improved behavioural, biochemical and histopathological changes, and reduced water content and infarct size. However, piracetam only improved behavioural and histopathological changes, reduced water content and infarct size. The findings indicate that silymarin exhibits neuroprotective activity better than PCA and piracetam in focal ischemia/reperfusion reflected by its better restoration of behavioural and antioxidant profile. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Therapeutic effects of different durations of acupuncture on rats with middle cerebral artery occlusion

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2015-01-01

    Full Text Available Acupuncture is regarded as an effective therapy for cerebral ischemia. Different acupuncture manipulations and durations may result in different therapeutic effects. In the present study, the Neiguan (PC6 acupoint of rats with occluded middle cerebral arteries was needled at a fixed frequency (3 Hz with different durations, i.e., 5, 60 and 180 seconds under a twisting-rotating acupuncture method. Results showed that different durations of acupuncture had different therapeutic effects, with 60 seconds yielding a better therapeutic effect than the other two groups. This duration of treatment demonstrated rapid cerebral blood flow, encouraging recovery of neurological function, and small cerebral infarct volume. Experimental findings indicated that under 3 Hz frequency, the treatment of needling Neiguan for 60 seconds is effective for ischemic stroke

  19. Correlation between synaptic plasticity, associated proteins, and rehabilitation training in a rat model of cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Dan Yang; Qian Yu

    2008-01-01

    All motions provide sensory, motoric, and reflexive input to the central nervous system, as well as playing an important role in cerebral functional plasticity and compensation. Cerebral plasticity has become the theoretical basis of neurorehabilitation. Studies of cerebrovascular disease, in particular, demonstrate that regeneration is accompanied by multiple forms of plasticity, such as functional and structural, in different phases of stroke rehabilitation. This study was designed to measure synaptic plasticity and expression of associated proteins to analyze the effect of rehabilitation training on learning and memory in a rat model of cerebral infarction. Results suggest that rehabilitation training increases expression of nerve growth factor associated protein 43, brain-derived neurotrophic factor, and neural cell adhesion molecules, and also promotes cerebral functional plasticity.

  20. Microcirculatory Impairment Following Focal and Global Cerebral Ischemia in the Rat.

    Science.gov (United States)

    1982-02-08

    intervals during isotope infusion. At I min the circulation was arrested by decapitation. The brain was quickly V 5 removed and frozen in isopentane...as blood pressure remains normal ŕ . When combined with prior electrocoagulation of the vertebral arteries, bilateral ligation of the common carotids...artery was electrocoagulated and the foramina packed with bone wax. The tissues were closed in layers. Through a midventral incision in the neck

  1. Effects of MK-801 upon local cerebral glucose utilization in conscious rats and in rats anaesthetised with halothane

    International Nuclear Information System (INIS)

    Kurumaji, A.; McCulloch, J.

    1989-01-01

    The effects of MK-801 (0.5 mg/kg i.v.), a non-competitive N-methyl-D-aspartate (NMDA) antagonist, upon local cerebral glucose utilization were examined in conscious, lightly restrained rats and in rats anaesthetised with halothane in nitrous oxide by means of the quantitative autoradiographic [14C]-2-deoxyglucose technique. In the conscious rats, MK-801 produced a heterogenous pattern of altered cerebral glucose utilization with significant increases being observed in 12 of the 28 regions of gray matter examined and significant decreases in 6 of the 28 regions. Pronounced increases in glucose use were observed after MK-801 in the olfactory areas and in a number of brain areas in the limbic system (e.g., hippocampus molecular layer, dentate gyrus, subicular complex, posterior cingulate cortex, and mammillary body). In the cerebral cortices, large reductions in glucose use were observed after administration of MK-801, whereas in the extrapyramidal and sensory-motor areas, glucose use remained unchanged after MK-801 administration in conscious rats. In the halothane-anaesthetised rats, the pattern of altered glucose use after MK-801 differed qualitatively and quantitatively from that observed in conscious rats. In anaesthetised rats, significant reductions in glucose use were noted after MK-801 in 10 of the 28 regions examined, with no area displaying significantly increased glucose use after administration of the drug. In halothane-anaesthetised rats, MK-801 failed to change the rates of glucose use in the olfactory areas, the hippocampus molecular layer, and the dentate gyrus

  2. Hemorrhagic Transformation After Large Cerebral Infarction in Rats Pretreated With Dabigatran or Warfarin.

    Science.gov (United States)

    Kwon, Il; An, Sunho; Kim, Jayoung; Yang, Seung-Hee; Yoo, Joonsang; Baek, Jang-Hyun; Nam, Hyo Suk; Kim, Young Dae; Lee, Hye Sun; Choi, Hyun-Jung; Heo, Ji Hoe

    2017-10-01

    It is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is less frequent in dabigatran users than warfarin users. We compared the occurrence of HT after large cerebral infarction among rats pretreated with dabigatran, warfarin, or placebo. This was a triple-blind, randomized, and placebo-controlled experiment. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or saline for 7 days, Wistar rats were subjected to transient middle cerebral artery occlusion. As the primary outcome, HT was determined by gradient-recalled echo imaging. For the secondary outcome, intracranial hemorrhage was assessed via gradient-recalled echo imaging in surviving rats and via autopsy for dead rats. Of 62 rats, there were 33 deaths (53.2%, 17 technical reasons). Of the intention-to-treat population, 33 rats underwent brain imaging. HT was less frequent in the dabigatran group than the warfarin group (placebo 2/14 [14%], dabigatran 0/10 [0%], and warfarin 9/9 [100%]; dabigatran versus warfarin; P warfarin group (19/29 [65.5%]; P =0.003), but not in the dabigatran group (6/19 [31.6%]; P =0.420). Mortality was significantly higher in the warfarin group than the dabigatran group (79.3% versus 47.4%; P =0.022), but not related to the hemorrhage frequency. The risk of HT after a large cerebral infarction was significantly increased in rats pretreated with warfarin than those with dabigatran. However, the results here may not have an exact clinical translation. © 2017 American Heart Association, Inc.

  3. Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

    Science.gov (United States)

    Okamura, Koichi; Tsubokawa, Tamiji; Johshita, Hiroo; Miyazaki, Hiroshi; Shiokawa, Yoshiaki

    2014-01-01

    Thrombolysis due to acute ischemic stroke is associated with the risk of hemorrhagic infarction, especially after reperfusion. Recent experimental studies suggest that the main mechanism contributing to hemorrhagic infarction is oxidative stress caused by disruption of the blood-brain barrier. Edaravone, a free radical scavenger, decreases oxidative stress, thereby preventing hemorrhagic infarction during ischemia and reperfusion. In this study, we investigated the effects of edaravone on hemorrhagic infarction in a rat model of hemorrhagic transformation. We used a previously established hemorrhagic transformation model of rats with hyperglycemia. Hyperglycemia was induced by intraperitoneal injection of glucose to all rats (n  =  20). The rats with hyperglycemia showed a high incidence of hemorrhagic infarction. Middle cerebral artery occlusion (MCAO) for 1.5 hours followed by reperfusion for 24 hours was performed in edaravone-treated rats (n  =  10) and control rats (n  =  10). Upon completion of reperfusion, both groups were evaluated for infarct size and hemorrhage volume and the results obtained were compared. Edaravone significantly decreased infarct volume, with the average infarct volume in the edaravone-treated rats (227.6 mm(3)) being significantly lower than that in the control rats (264.0 mm(3)). Edaravone treatment also decreased the postischemic hemorrhage volumes (53.4 mm(3) in edaravone-treated rats vs 176.4 mm(3) in controls). In addition, the ratio of hemorrhage volume to infarct volume was lower in the edaravone-treated rats (23.5%) than in the untreated rats (63.2%). Edaravone attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

  4. Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats

    DEFF Research Database (Denmark)

    Hansen, M B; Olsen, Niels Vidiendal; Hyldegaard, O

    2013-01-01

    -to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 k......Pa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations...

  5. Cerebral ischemia produced by four-vessel occlusion in the rat: a quantitative evaluation of cerebral blood flow

    International Nuclear Information System (INIS)

    Furlow, T.W. Jr.

    1982-01-01

    Cerebral ischemia was produced in the rat by simultaneous occlusion of the vertebral and carotid arteries according to the method of Pulsinelli and Brierley (Stroke 10: 267, 1979). Local cerebral blood flow (CBF) was determined by polarographic and autoradiographic techniques. Hydrogen-clearance measurements showed that mean CBF fell in four monitored regions of the hemispheres to between 0.11 and 0.18 ml/g/min, being least in deep rostal gray, intermediate in superficial gray, and greatest in deep caudal gray. However, individual animals had local CBF in excess of 0.20 and even 0.30 ml/g/min, and no animal showed zero CBF. When animals were rendered hypotensive (MABP of 50 Torr) during vascular occlusion, mean CBF ranged between 0.03 and 0.10 ml/g/min in the same regional order. With hypotension, total arrest of flow occurred. Autoradiographic data confirmed the above findings and indicated adequate CBF to the lower brainstem. During vascular occlusion, sufficient CBF may be present ot sustain cerebral tissue as in animals with a well developed spinal circulation or an inadvertently patent vertebral artery

  6. The Effects of Repeated Rehabilitation “Tune-Ups” on Functional Recovery After Focal Ischemia in Rats

    DEFF Research Database (Denmark)

    Clarke, Jared; Rytter, Hana Malá; Windle, Victoria

    2009-01-01

    of stroke recovery. Methods. Rats were exposed to focal ischemia (endothelin-1 applied to forelimb sensorimotor cortex and dorsolateral striatum) and allowed to recover either in standard housing or in a combination of enriched environment and rehabilitative reaching for 9 weeks. Animals were then exposed...... complexity in the contralesional forelimb motor cortex. Results. Although early enriched rehabilitation significantly improved sensorimotor function in both the beam and staircase tests, “tune-up” therapy had no effect on recovery. Golgi–Cox analysis revealed no effect of treatment on dendritic complexity...

  7. Focal treatment of spasticity using botulinum toxin A in cerebral palsy cases of GMFCS level V: evaluation of adverse effects

    Directory of Open Access Journals (Sweden)

    Ana Paula Tedesco

    2014-08-01

    Full Text Available Objective:To report on the experience of injections of botulinum toxin A (BTA in a series of patients with cerebral palsy of Gross Motor Function Classification System (GMFCS level V.Methods:This was a retrospective case series study on 33 patients with cerebral palsy of GMFCS level V who received 89 sessions of BTA application (of which 84 were Botox® and five were other presentations, in which the basic aim was to look for adverse effects.Results:The mean number of application sessions per patient was three, and the mean age at the time of each injection was 4 + 6 years (range: 1.6–13 years. The muscles that most frequently received injections were the gastrocnemius, hamstrings, hip adductors, biceps brachii and finger flexors. The mean total dose was 193 U and the mean dose per weight was 12.5 U/kg. Only one patient received anesthesia for the injections and no sedation was used in any case. No local or systemic adverse effects were observed within the minimum follow-up of one month.Conclusion:The absence of adverse effects in our series was probably related to the use of low doses and absence of sedation or anesthesia. According to our data, BTA can be safely used for patients with cerebral palsy of GMFCS level V, using low doses and preferably without sedation or anesthesia.

  8. Análisis comparativo de marcadores de lesión en modelos de isquemia cerebral focal y global en ratas

    Directory of Open Access Journals (Sweden)

    Ángel Enrique Céspedes

    2013-06-01

    Full Text Available Introducción. Los indicadores espacio-temporales de lesión son esenciales en el estudio neuropatológico y terapéutico de la isquemia cerebral. Objetivo. Optimizar la técnica de dos modelos de isquemia cerebral (focal y global y hacer un análisis comparativo de la progresión del daño cerebral, mediante marcadores de neurodegeneración. Materiales y métodos. Se sometieron ratas Wistar a oclusión temporal de la arteria cerebral media o aoclusión de cuatro vasos, y se evaluaron comparativamente el tiempo quirúrgico, la tasa de supervivenciay la recuperación neurológica. Se utilizó trifenilo de tetrazolio para establecer la distribución del infarto y tinción con Fluoro-Jade B® como marcador de neurodegeneración. La inmunorreacción de la astroglía  se evaluó con el anticuerpo contra la proteína acídica fibrilar de la glía (Glial Fibrillary Acidic Protein,GFAP y el anticuerpo AT-8 contra la proteína tau hiperfosforilada, 24, 48 y 72 horas después de la isquemia. Resultados. Los modelos de isquemia utilizados requirieron menor tiempo quirúrgico y hubo menorriesgo de muerte, respecto a estudios previos. En el modelo focal, las células positivas con Fluoro-Jade B® y los astrocitos reactivos, se evidenciaron en corteza e hipocampo a las 24 horas después de la isquemia. En el modelo global, se observó tinción Fluoro-Jade B® positiva a las 24 horas, aumentando significativamente la reacción de la GFAP a las 72 horas en corteza y a las 48 horas en el hipocampo. La reacción contra la proteína tau hiperfosforilada aumentó progresivamente y fue máxima a las 72horas en ambos modelos. Conclusiones. Los dos modelos de isquemia cerebral, oclusión temporal de la arteria cerebral media y oclusión de cuatro vasos, fueron optimizados. En estos modelos, los marcadores la tinción Fluoro-Jade B® y la GFAP permitieron detectar procesos de neurodegeneración 24 horas después de la isquemia, en tanto el marcador de proteína tau

  9. Alterations in the Cerebral Microvascular Proteome Expression Profile After Transient Global Cerebral Ischemia in Rat

    DEFF Research Database (Denmark)

    Spray, Stine; Johansson, Sara E; Edwards, Alistair V G

    2017-01-01

    . The proteomic profile of the isolated cerebral microvasculature 72 h after GCI (compared to sham) indicated that the main expressional changes could be divided into nine categories: (1) cellular respiration, (2) remodelling of the extracellular matrix, (3) decreased contractile phenotype, (4) clathrin...

  10. Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats.

    Science.gov (United States)

    Ahmed, Maha A E; El Morsy, Engy M; Ahmed, Amany A E

    2014-08-21

    Interruption to blood flow causes ischemia and infarction of brain tissues with consequent neuronal damage and brain dysfunction. Pomegranate extract is well tolerated, and safely consumed all over the world. Interestingly, pomegranate extract has shown remarkable antioxidant and anti-inflammatory effects in experimental models. Many investigators consider natural extracts as novel therapies for neurodegenerative disorders. Therefore, this study was carried out to investigate the protective effects of standardized pomegranate extract against cerebral ischemia/reperfusion-induced brain injury in rats. Adult male albino rats were randomly divided into sham-operated control group, ischemia/reperfusion (I/R) group, and two other groups that received standardized pomegranate extract at two dose levels (250, 500 mg/kg) for 15 days prior to ischemia/reperfusion (PMG250+I/R, and PMG500+I/R groups). After I/R or sham operation, all rats were sacrificed and brains were harvested for subsequent biochemical analysis. Results showed reduction in brain contents of MDA (malondialdehyde), and NO (nitric oxide), in addition to enhancement of SOD (superoxide dismutase), GPX (glutathione peroxidase), and GRD (glutathione reductase) activities in rats treated with pomegranate extract prior to cerebral I/R. Moreover, pomegranate extract decreased brain levels of NF-κB p65 (nuclear factor kappa B p65), TNF-α (tumor necrosis factor-alpha), caspase-3 and increased brain levels of IL-10 (interleukin-10), and cerebral ATP (adenosine triphosphate) production. Comet assay showed less brain DNA (deoxyribonucleic acid) damage in rats protected with pomegranate extract. The present study showed, for the first time, that pre-administration of pomegranate extract to rats, can offer a significant dose-dependent neuroprotective activity against cerebral I/R brain injury and DNA damage via antioxidant, anti-inflammatory, anti-apoptotic and ATP-replenishing effects. Copyright © 2014 Elsevier Inc

  11. Cerebral energy metabolism in streptozotocin-diabetic rats

    NARCIS (Netherlands)

    Biessels, G.J.; Braun, K.P.J.; Graaf, de R.A.; Eijsden, van P.; Gispen, W.H.; Nicolaij, K.

    2001-01-01

    Aims/hypothesis. It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood

  12. Subarachnoid hemorrhage enhances endothelin receptor expression and function in rat cerebral arteries

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Hoel, Natalie Løvland; Zhou, Mingfang

    2003-01-01

    OBJECTIVE: Inspired by organ culture-induced changes in the vascular endothelin (ET) receptor population, we investigated whether such changes occur in cerebral arteries in a rat subarachnoid hemorrhage (SAH) model. METHODS: SAH was induced with injection of 250 microl of blood into the prechiasm......OBJECTIVE: Inspired by organ culture-induced changes in the vascular endothelin (ET) receptor population, we investigated whether such changes occur in cerebral arteries in a rat subarachnoid hemorrhage (SAH) model. METHODS: SAH was induced with injection of 250 microl of blood...... into the prechiasmatic cistern. After 2 days, the middle cerebral artery, basilar artery, and posterior communicating artery were harvested. Pharmacological studies were performed in vitro, and levels of messenger ribonucleic acid (mRNA) were quantified in real-time reverse transcriptase-polymerase chain reaction assays....... RESULTS: In the middle cerebral artery and basilar artery from rats with induced SAH, enhanced biphasic responses to ET-1 were observed. The -log(50% effective concentration) value for the high-affinity phase was approximately 12, compared with approximately 8.5 for sham-operated animals...

  13. Lesion Size Is Exacerbated in Hypoxic Rats Whereas Hypoxia-Inducible Factor-1 Alpha and Vascular Endothelial Growth Factor Increase in Injured Normoxic Rats: A Prospective Cohort Study of Secondary Hypoxia in Focal Traumatic Brain Injury.

    Science.gov (United States)

    Thelin, Eric Peter; Frostell, Arvid; Mulder, Jan; Mitsios, Nicholas; Damberg, Peter; Aski, Sahar Nikkhou; Risling, Mårten; Svensson, Mikael; Morganti-Kossmann, Maria Cristina; Bellander, Bo-Michael

    2016-01-01

    Hypoxia following traumatic brain injury (TBI) is a severe insult shown to exacerbate the pathophysiology, resulting in worse outcome. The aim of this study was to investigate the effects of a hypoxic insult in a focal TBI model by monitoring brain edema, lesion volume, serum biomarker levels, immune cell infiltration, as well as the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Female Sprague-Dawley rats (n = 73, including sham and naive) were used. The rats were intubated and mechanically ventilated. A controlled cortical impact device created a 3-mm deep lesion in the right parietal hemisphere. Post-injury, rats inhaled either normoxic (22% O2) or hypoxic (11% O2) mixtures for 30 min. The rats were sacrificed at 1, 3, 7, 14, and 28 days post-injury. Serum was collected for S100B measurements using ELISA. Ex vivo magnetic resonance imaging (MRI) was performed to determine lesion size and edema volume. Immunofluorescence was employed to analyze neuronal death, changes in cerebral macrophage- and neutrophil infiltration, microglia proliferation, apoptosis, complement activation (C5b9), IgG extravasation, HIF-1α, and VEGF. The hypoxic group had significantly increased blood levels of lactate and decreased pO2 (p hypoxic animals (p hypoxic group at 1 day after trauma (p = 0.0868). No differences were observed between the groups in cytotoxic and vascular edema, IgG extravasation, neutrophils and macrophage aggregation, microglia proliferation, or C5b-9 expression. Hypoxia following focal TBI exacerbated the lesion size and neuronal loss. Moreover, there was a tendency to higher levels of S100B in the hypoxic group early after injury, indicating a potential validity as a biomarker of injury severity. In the normoxic group, the expression of HIF-1α and VEGF was found elevated, possibly indicative of neuro-protective responses occurring in this less severely injured group. Further studies are

  14. Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries.

    Science.gov (United States)

    Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V; Busija, David W

    2015-11-01

    Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using N(ω)-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I-V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury. Copyright © 2015 the American Physiological Society.

  15. Effects of captopril on cerebral blood flow in normotensive and hypertensive rats

    International Nuclear Information System (INIS)

    Barry, D.I.; Paulson, O.B.; Jarden, J.O.; Juhler, M.; Graham, D.I.; Strandgaard, S.

    1984-01-01

    Cerebrovascular effects of the angiotensin converting enzyme inhibitor captopril were examined in normotensive and hypertensive rats. Cerebral blood flow was measured with the intracarotid 133 xenon injection method in halothane-anesthetized animals. The blood-brain barrier permeability of captopril (determined with an integral-uptake method) was negligible, the permeability-surface area product in most brain regions being 1 X 10(-5) cm3/g per second, that is, three to four times lower than that of sodium ion. When administered into the cerebral ventricles to bypass the blood-brain barrier, captopril had no effect on cerebral blood flow: furthermore, cerebral blood flow autoregulation (studied by raising and lowering blood pressure) was identical to that in controls. In contrast, when given intravenously, captopril had a marked effect on cerebral blood flow autoregulation--both the lower and upper limits of autoregulation being shifted to a lower pressure (by about 20 to 30 and 50 to 60 mm Hg, respectively), and the autoregulatory range was shortened by about 40 mm Hg. This effect may be ascribed to inhibition of converting enzyme in the cerebral blood vessels rather than within the brain

  16. Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

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    Erol-Demirbilek Melike

    2016-09-01

    Full Text Available Background: Thioredoxin reductase (TrxR, epidermal growth factor (EGF and tumor necrosis factor-α (TNF-α have neuroprotective/neurotoxic effects in cerebral ischemia. We aimed to investigate the TrxR activity, EGF and TNF-α levels in cerebral ischemic, sham-operated and non-ischemic rat brains.

  17. Changes of cerebral contents of neuropeptides in rat models of multiple ischemic dementia (MID)

    International Nuclear Information System (INIS)

    Zheng Xianghong; Guo Jingcai; Song Changyi; Wang Shejiao; Chen Wei

    2005-01-01

    Objective: To investigate the significance of changes of cerebral contents of the neuropeptides somatostatin (SS), arginine vasopressin (AVP) and substance P in rat models of MID. Methods: The rat models consisted of 15 rats undergoing intracarotid injection of autogenous thrombus powder. Another group of 15 rats undergoing sham operation served as controls. Learning and memory ability in these rats was assessed with daily passive avoidance task testing for 10 consecutive days. The animals were sacrificed on 30d and contents of the neuropeptides in tissue homogenate from different areas of brain (frontal cortex, temporal cortex, hippocampus, thalamus and corpus striatum) were measured with (RIA). Results: On the first day of passive avoidance task testing, the frequency of errors in the MID group and the control group was about the same. From the third day on, the frequency of errors in the MID group was significantly higher than that in the control group (P<0.05). The neuropeptides contents of all these cerebral areas in the MID group were significantly higher than those in the control group (P<0.05 or P<0.01) with the only exception of the contents of substance P in thalamus (no significant difference between the contents in the two groups). Conclusion: The impairment of learning and memory in rat models with MID was possibly related to the lowered contents of SS, AVP and substance P in the brain tissue. (authors)

  18. The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats

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    Lei Zhang

    2016-01-01

    Full Text Available The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB on ischemic cerebral infarction (stroke, by using an animal model of transient middle cerebral artery occlusion (MCAO. Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB.

  19. Effects of Edaravone, a Free Radical Scavenger, on Photochemically Induced Cerebral Infarction in a Rat Hemiplegic Model

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    Ikeda, Satoshi; Harada, Katsuhiro; Ohwatashi, Akihiko; Kamikawa, Yurie

    2013-01-01

    Edaravone is a free radical scavenger that protects the adjacent cortex during cerebral infarction. We created a hemiparetic model of cerebral thrombosis from a photochemically induced infarction with the photosensitive dye, rose bengal, in rats. We examined the effects of edaravone on recovery in the model. A total of 36 adult Wistar rats were used. The right sensorimotor area was irradiated with green light with a wavelength of 533?nm (10?mm diameter), and the rose bengal was injected intra...

  20. Protective effects of geniposide and ginsenoside Rg1 combination treatment on rats following cerebral ischemia are mediated via microglial microRNA‑155‑5p inhibition.

    Science.gov (United States)

    Wang, Jun; Li, Dan; Hou, Jincai; Lei, Hongtao

    2018-02-01

    Geniposide, an active component of Gardenia, has been reported to protect against cerebral ischemia in animals. Ginsenoside Rg1, a component of Panax notoginseng, is usually administered in combination with Gardenia for the treatment of acute ischemic stroke; however, there are unknown effects of ginsenoside Rg1 that require further investigation. In the present study, the effects of geniposide and ginsensoide Rg1 combination treatment on focal cerebral ischemic stroke were investigated. For in vivo analysis, male rats were separated into three groups, including the (control), model and geniposide + ginsenoside Rg1 groups (n=8 per group). A middle cerebral artery occlusion model was established as the model group. The treatment group was treated with geniposide (30 mg/kg, tail vein injection) + ginsenoside Rg1 (6 mg/kg, tail vein injection), and the model group received saline instead. Neurobehavioral deficits, infarct volume, brain edema, and the expression of microRNA (miR)‑155‑5p and CD11b by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry, were assessed following 24 h of ischemia. For in vitro analysis, BV2 mouse microglial cells were cultured and exposed to geniposide (40 µg/ml) + ginsenoside Rg1 (8 µg/ml) during various durations of oxygen‑glucose deprivation (OGD). The expression levels of miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 were detected by RT‑qPCR. The results demonstrated that increases in brain infarct volume, edema volume, CD11b‑positive cells and miR‑155‑5p levels were alleviated following geniposide + ginsenoside administration in rats exposed to ischemia. Furthermore, geniposide + ginsenoside Rg1 treatment suppressed the miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 expression levels in OGD‑injured BV2 microglial cells. The results of the present study demonstrated that tail vein administration of geniposide in combination with ginsenoside Rg1

  1. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

    Science.gov (United States)

    Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

    2013-08-15

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  2. Impact of treatment with melatonin on cerebral circulation in old rats

    Science.gov (United States)

    Dupuis, François; Régrigny, Olivier; Atkinson, Jeffrey; Limiñana, Patrick; Delagrange, Philippe; Scalbert, Elizabeth; Chillon, Jean-Marc

    2004-01-01

    Melatonin deprival in young rats induces alterations in cerebral arteriolar wall similar to those observed during aging: atrophy and a decrease in distensibility. In this study, we examined the effects of melatonin treatment on cerebral arteriolar structure and distensibility and on the lower limit of cerebral blood flow autoregulation (LLCBF) in old rats. We measured cerebral blood flow (arbitrary unit, laser Doppler, open skull preparation) prior to and during stepwise hypotension (SH) in adult (12/13 months) and old (24/25 months) IcoWI and WAG/Rij male rats. Old rats were untreated or treated for 3 months with melatonin (0.39 (IcoWi) and 0.44 (Wag/Rij) mg kg−1 day−1, drinking water). Stress–strain relationships were determined using cross-sectional area (CSA, μm2, histometry) and values of arteriolar internal diameter (μm) obtained during a second SH following arteriolar deactivation (EDTA, 67 mmol l−1). Aging induced (a) atrophy of the arteriolar wall in IcoWI (616±20 vs 500±27 μm2, P<0.05) but not in WAG/Rij rats (328±25 vs 341±20 μm2), (b) a decrease in arteriolar wall distensibility and (c) an increase in the LLCBF in both strains (67±10 mmHg in 12-month-old vs 95±6 mmHg in 24-month-old IcoWi, P<0.05 and 53±2 mmHg in 13-month-old vs 67±6 mmHg in 25-month-old WAG/Rij). Melatonin treatment induced in IcoWI and WAG/Rij rats (a) hypertrophy of the arteriolar wall (643±34 and 435±25 μm2, respectively), (b) an increase in arteriolar wall distensibility and (c) a decrease in the LLCBF (64±6 and 45±4 mmHg, respectively). Melatonin treatment of old rats induced hypertrophy of the arteriolar wall, prevented the age-linked decrease in cerebral arteriolar distensibility and decreased the LLCBF. PMID:14718260

  3. Effect of sevoflurane on the ATPase activity of hippocampal neurons in a rat model of cerebral ischemia-reperfusion injury via the cAMP-PKA signaling pathway.

    Science.gov (United States)

    Liu, Tie-Jun; Zhang, Jin-Cun; Gao, Xiao-Zeng; Tan, Zhi-Bin; Wang, Jian-Jun; Zhang, Pan-Pan; Cheng, Ai-Bin; Zhang, Shu-Bo

    2018-01-01

    We aim to investigate the effects of sevoflurane on the ATPase activity of the hippocampal neurons in rats with cerebral ischemia-reperfusion injury (IRI) via the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) signaling pathway. Sixty rats were assigned into the normal, model and sevoflurane groups (n = 20, the latter two groups were established as focal cerebral IRI models). The ATPase activity was detected using an ultramicro Na (+)-K (+)-ATP enzyme kit. Immunohistochemical staining was used to detect the positive protein expression of cAMP and PKA. The hippocampal neurons were assigned to the normal, IRI, IRI + sevoflurane, IRI + forskolin, IRI + H89 and IRI + sevoflurane + H89 groups. qRT-PCR and Western blotting were performed for the expressions of cAMP, PKA, cAMP-responsive element-binding protein (CREB) and brain derived neurotrophic factor (BDNF). The normal and sevoflurane groups exhibited a greater positive protein expression of cAMP and PKA than the model group. Compared with the normal group, the expressions of cAMP, PKA, CREB and BDNF all reduced in the IRI, model and IRI + H89 groups. The sevoflurane group showed higher cAMP, PKA, CREB and BDNF expressions than the model group. Compared with the IRI group, ATPase activity and expressions of cAMP, PKA, CREB and BDNF all increased in the normal, IRI + sevoflurane and IRI + forskolin groups but decreased in the IRI + H89 group. It suggests that sevoflurane could enhance ATPase activity in hippocampal neurons of cerebral IRI rats through activating cAMP-PKA signaling pathway. Copyright © 2017. Published by Elsevier Taiwan.

  4. The effects of low dose ionizing radiation on the development of rat cerebral cortex, (2)

    International Nuclear Information System (INIS)

    Matsushita, Koji

    1993-01-01

    In order to study the molecular mechanisms of neuronal migration on developing rat cerebral cortex, we need a tissue culture system in which neuronal migration can be observed. We prepared a tissue culture system of embryonic rat cerebral cortex starting on embryonic day 16 and cultivating it for 48 hours. The autoradiographic study in this system revealed not only the migration of 3 H-thymidine labeled neurons but also neuronal migration delays from low doses of ionizing radiation of more than 10 cGy. In addition, on immunohistochemical study, cell-cell adhesion molecule N-CAM staining was remarkably decreased in the matrix cell layer. In the tissue culture system where monoclonal anti-N-CAM antibodies were added, neuronal migration delay comparable to that of 20 cGy radiation was found. In conclusion, it was speculated that neuronal migration delay might be caused by disturbed N-CAM synthesis in matrix cells after low dose ionizing radiation. (author)

  5. Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia

    International Nuclear Information System (INIS)

    Beck, T.; Krieglstein, J.

    1987-01-01

    The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O 2 . Hypoxia affected a marked hypotension, hypocapnia and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate lactate, and pyruvate levels were significantly increased. Blood-brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40-70% of control values in gray matter and by 80-90% in white matter. Under hypoxia, columns of increased and decreased LCGU and were detectable in cortical gray matter. Color-coded [ 14 C]2-deoxy-D-glucose autoradiograms of rat brain are shown. Local cerebral blood flow (LCBF) increased by 50-90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggests a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur

  6. Effect of camphor essential oil on rat cerebral cortex activity as manifested by fractal dimension changes

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    Grbić G.

    2008-01-01

    Full Text Available The aim of our study was to investigate the effect of camphor essential oil on rat cerebral cortex activity by fractal analysis. Fractal dimension (FD values of the parietal electrocortical activity were calculated before and after intra-peritoneal administration of camphor essential oil (450-675 μl/kg in anesthetized rats. Camphor oil induced seizure-like activity with single and multiple spiking of high amplitudes in the parietal electrocorticogram and occasional clonic limb convulsions. The FD values of cortical activity after camphor oil administration increased on the average. Only FD values of cortical ECoG sequences were lower than those before camphor oil administration.

  7. Upregulation of neuronal zinc finger protein A20 expression is required for electroacupuncture to attenuate the cerebral inflammatory injury mediated by the nuclear factor-kB signaling pathway in cerebral ischemia/reperfusion rats.

    Science.gov (United States)

    Zhan, Jian; Qin, Wenyi; Zhang, Ying; Jiang, Jing; Ma, Hongmei; Li, Qiongli; Luo, Yong

    2016-10-03

    Zinc finger protein A20 (tumor necrosis factor alpha-induced protein 3) functions as a potent negative feedback inhibitor of the nuclear factor-kB (NF-kB) signaling. It exerts these effects by interrupting the activation of IkB kinase beta (IKKβ), the most critical kinase in upstream of NF-kB, and thereby controlling inflammatory homeostasis. We reported previously that electroacupuncture (EA) could effectively suppress IKKβ activation. However, the mechanism underlying these effects was unclear. Therefore, the current study further explored the effects of EA on A20 expression in rat brain and investigated the possible mechanism of A20 in anti-neuroinflammation mediated by EA using transient middle cerebral artery occlusion (MCAO) rats. Rats were treated with EA at the "Baihui (GV20)," "Hegu (L14)," and "Taichong (Liv3)" acupoints once a day starting 2 h after focal cerebral ischemia. The spatiotemporal expression of A20, neurobehavioral scores, infarction volumes, cytokine levels, glial cell activation, and the NF-kB signaling were assessed at the indicated time points. A20 gene interference (overexpression and silencing) was used to investigate the role of A20 in mediating the neuroprotective effects of EA and in regulating the interaction between neuronal and glial cells by suppressing neuronal NF-kB signaling during cerebral ischemia/reperfusion-induced neuroinflammation. EA treatment increased A20 expression with an earlier peak and longer lasting upregulation. The upregulated A20 protein was predominantly located in neurons in the cortical zone of the ischemia/reperfusion. Furthermore, neuronal A20 cell counts were positively correlated with neurobehavioral scores but negatively correlated with infarct volume, the accumulation of pro-inflammatory cytokines, and glial cell activation. Moreover, the effects of EA on improving the neurological outcome and suppressing neuroinflammation in the brain were reversed by A20 silencing. Finally, A20 silencing also

  8. Nylon filament coated with paraffin for intraluminal permanent middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Zuo, Xia-Lin; Wu, Ping; Ji, Ai-Min

    2012-06-21

    A variety of intraluminal nylon filament has been used in rat middle cerebral artery occlusion (MCAO) models. However the lesion extent and its reproducibility vary among laboratories. The properties of nylon filament play a part of reasons for these variations. In the present study, we used paraffin-coated nylon filament for rat MCAO model, tested the effects and advanced improvement for making the rat MCAO. Forty male Sprague-Dawley (SD) rats were randomized into two groups, MCAO with traditional uncoated nylon filament (uMCAO) and MCAO with paraffin-coated nylon filament (cMCAO), three rats as normal group and sham group respectively. Assessment included mortality rates, model success rates, neurological deficit evaluation, and infarct volume. The study showed two rats died in uMCAO group, no rat died in cMCAO group within the 12h. The model success rate of uMCAO was 100%, while the uMCAO group was 55% (n=20, two died within 12h, seven rats were excluded as the brain slices showed no TTC staining due to subarachanoid hemorrhage). Neurological evaluation demonstrated group cMCAO had more worse neurological outcomes than group uMCAO, and the difference was statistically signification (pparaffin-coated nylon filament intraluminal occlusion provide better occlusion of middle cerebral artery than the uncoated nylon filament, improve the consistent of model, and raise the success rate to reduce the number of experimental animals. These positive results are much encouraging and interesting. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Cerebral blood flow and oxygen consumption during ethanol withdrawal in the rat.

    Science.gov (United States)

    Hemmingsen, R; Barry, D I; Hertz, M M; Klinken, L

    1979-09-14

    The ethanol withdrawal syndrome in man and animals is characterized by signs of CNS hyperactivity although a direct measurement of a physiological variable reflecting this CNS hyperactivity has never been performed in untreated man or in animals. We induced ethanol dependence in the rat by means of intragastric intubation with a 20% w/v ethanol solution, thus keeping the animals in a state of continuous severe intoxication for 3--4 days; during the subsequent state of withdrawal characterized by tremor, rigidity, stereotyped movements and general seizures a 25% increase in cerebral oxygen consumption (CMRO2) could be measured; this increase was not due to catecholamines originating from adrenal medulla as adrenomedullectomized animals showed a similar increase in CMRO2 (28%); the withdrawing animals showed a corresponding cerebral blood flow (CBF) increase. The elevated CMRO2 and CBF could be reduced to normal by administration of a beta-adrenergic receptor blocker (propranolol 2 mg/kg i.v.), and hence the increased CMRO2 during ethanol withdrawal could be related to catecholaminergic systems in the brain, e.g. the noradrenergic locus coeruleus system which is anatomically well suited as a general activating system. This interpretation is supported by the earlier neurochemical finding of an increased cerebral noradrenaline turnover during ethanol withdrawal. The exact mechanism underlying the increased cerebral oxygen consumption during ethanol withdrawal and the effect of propranolol on cerebral function during this condition remains to be clarified.

  10. Effects of apomorphine upon local cerebral glucose utilization in conscious rats and in rats anesthetized with chloral hydrate

    Energy Technology Data Exchange (ETDEWEB)

    Grome, J.J.; McCulloch, J.

    1983-02-01

    The effects of the dopaminergic agonist apomorphine upon local cerebral glucose utilization in 43 anatomically discrete regions of the CNS were examined in conscious, lightly restrained rats and in rats anesthetized with chloral hydrate by means of the quantitative autoradiographic (/sup 14/C)2-deoxyglucose technique. In animals anesthetized with chloral hydrate, glucose utilization was reduced throughout all regions of the CNS from the levels observed in conscious animals. With chloral hydrate anesthesia, the proportionately most marked reductions in glucose use were noted in primary auditory nuclei, thalmaic relay nuclei, and neocortex, and the least pronounced reductions in glucose use (by 15-25% from conscious levels) were observed in limbic areas, some motor relay nuclei, and white matter. In conscious, lightly restrained rats, the administration of apomorphine effected significant increases in glucose utilization in 15 regions of the CNS, and significant reductions in glucose utilization in two regions of the CNS. In rats anesthetized with chloral hydrate, the effects of apomorphine upon local glucose utilization were less widespread and less marked than in conscious animals. The profound effects of chloral hydrate anesthesia upon local cerebral glucose use, and the modification by this anesthetic regime of the local metabolic responses to apomorphine, emphasize the difficulties which exists in the extrapolation of data from anesthetized animals to the conditions which prevail in the conscious animal.

  11. Effects on locomotion and memory in 2 models of cerebral hypoperfusion in male Wistar rats.

    Science.gov (United States)

    Martínez-Díaz, J A; García, L I; Hernández, M E; Aranda-Abreu, G E

    2015-09-01

    Cerebral ischaemia is one of the most common neurological diseases worldwide. Its many sequelae range from motor and sensory symptoms to cognitive decline and dementia. Animal models of cerebral ischaemia/hypoperfusion elicit effects on long term memory; however, the effects of these procedures on short term memory are not clearly understood and effects induced by alternative hypoperfusion models are completely unknown. We evaluated the effects of 2 cerebral hyperperfusion models on memory in 3-month-old male rats. Episodic memory and working memory were assessed using the new object recognition test and the spontaneous alteration test, respectively. Neurological assessment was also performed, along with an open field test to evaluate locomotor activity. Rats in both hyperperfusion models displayed no cognitive changes. Rats with unilateral left-sided ligation plus temporary ligation of the right carotid tended to show slightly impaired performance on the new object recognition test on the second day after the procedure. In contrast, the group with permanent unilateral ligation tended to display alterations in working and episodic memory 9 days after the procedure, but they subsequently recovered. Despite these differences, both hypoperfusion groups displayed clear signs of motor impairment 2 days after the procedure, as reflected by their decreased locomotor activity during the open field test. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Neuroprotective Effect of Xueshuantong for Injection (Lyophilized in Transient and Permanent Rat Cerebral Ischemia Model

    Directory of Open Access Journals (Sweden)

    Xumei Wang

    2015-01-01

    Full Text Available Xueshuantong for Injection (Lyophilized (XST, a Chinese Materia Medica standardized product extracted from Panax notoginseng (Burk., is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction clinically in China. In the present study, we evaluated the acute and extended protective effects of XST in different rat cerebral ischemic model and explored its effect on peroxiredoxin (Prx 6-toll-like receptor (TLR 4 signaling pathway. We found that XST treatment for 3 days could significantly inhibit transient middle cerebral artery occlusion (MCAO induced infarct volume and swelling percent and regulate the mRNA expression of interleukin-1β (IL-1β, IL-17, IL-23p19, tumor necrosis factor-α (TNFα, and inducible nitric oxide synthase (iNOS in brain. Further study demonstrated that treatment with XST suppressed the protein expression of peroxiredoxin (Prx 6-toll-like receptor (TLR 4 and phosphorylation level of p38 and upregulated the phosphorylation level of STAT3. In permanent MCAO rats, XST could reduce the infarct volume and swelling percent. Moreover, our results revealed that XST treatment could increase the rats’ weight and improve a batch of functional outcomes. In conclusion, the present data suggested that XST could protect against ischemia injury in transient and permanent MCAO rats, which might be related to Prx6-TLR4 pathway.

  13. Investigation of Implantable Multi-Channel Electrode Array in Rat Cerebral Cortex Used for Recording

    Science.gov (United States)

    Taniguchi, Noriyuki; Fukayama, Osamu; Suzuki, Takafumi; Mabuchi, Kunihiko

    There have recently been many studies concerning the control of robot movements using neural signals recorded from the brain (usually called the Brain-Machine interface (BMI)). We fabricated implantable multi-electrode arrays to obtain neural signals from the rat cerebral cortex. As any multi-electrode array should have electrode alignment that minimizes invasion, it is necessary to customize the recording site. We designed three types of 22-channel multi-electrode arrays, i.e., 1) wide, 2) three-layered, and 3) separate. The first extensively covers the cerebral cortex. The second has a length of 2 mm, which can cover the area of the primary motor cortex. The third array has a separate structure, which corresponds to the position of the forelimb and hindlimb areas of the primary motor cortex. These arrays were implanted into the cerebral cortex of a rat. We estimated the walking speed from neural signals using our fabricated three-layered array to investigate its feasibility for BMI research. The neural signal of the rat and its walking speed were simultaneously recorded. The results revealed that evaluation using either the anterior electrode group or posterior group provided accurate estimates. However, two electrode groups around the center yielded poor estimates although it was possible to record neural signals.

  14. [Relation between expression of cerebral beta-APP in the chronic alcoholism rats and death caused by TSAH].

    Science.gov (United States)

    Wei, Lai; Lei, Huai-Cheng; Yu, Xiao-Jun; Lai, Xiao-Ping; Qian, Hong; Xu, Xiao-Hu; Zhu, Fang-Cheng

    2013-04-01

    By observing the cerebral beta-amyloid precursor protein (beta-APP) expression in the chronic alcoholism rats with slight cerebral injury, to discuss the correlation of chronic alcoholism and death caused by traumatic subarachnoid haemorrhage (TSAH). Sixty male SD rats were randomly divided into watering group, watering group with strike, alcoholism group and alcoholism group with strike. Among them, the alcohol was used for continuous 4 weeks in alcoholism groups and the concussion was made in groups with strike. In each group, HE staining and immunohistochemical staining of the cerebral tissues were done and the results were analyzed by the histopathologic image system. In watering group, there was no abnormal. In watering group with strike, mild neuronic congestion was found. In alcoholism group, vascular texture on cerebral surface was found. And the neurons arranged in disorder with dilated intercellular space. In alcoholism group with strike, diffuse congestion on cerebral surface was found. And there was TSAH with thick-layer patches around brainstem following irregular axonotmesis. The quantity of beta-APP IOD in alcoholism group was significantly higher in the frontal lobe, hippocampus, cerebellum, brainstem than those in watering group with strike and alcoholism group with strike. The cerebral tissues with chronic alcoholism, due to the decreasing tolerance, could cause fatal TSAH and pathological changes in cerebral tissues of rats under slight cerebral injury.

  15. Effects of a Single Dose of Erythropoietin on Motor Function and Cognition after Focal Brain Ischemia in Adult Rats

    Directory of Open Access Journals (Sweden)

    Michaela Hralová

    2014-01-01

    Full Text Available We tested the influence of erythropoietin (EPO, a basic cytokine in erythropoiesis regulation, on the process of motor function and cognition after focal brain ischemia induced by a local application of endothelin. Endothelin-1 (ET-1 induced short lasting strong vasoconstriction, with described impact on the structure and on the function of neuronal cells. Neurological description of motor function and Morris water maze test (the swimming test is one of most widely used methods for studying cognitive functions in rodents were used to study the process of learning and memory in three-month-old male albino Wistar rats (n=52. Both tests were performed one week before, and three weeks after ischemia induction (endothelin application on the cortex in the area of a. cerebri media dx.. Experimental group received i.p. injection of EPO (5,000 IU/kg body weight, 10 min before endothelin application. Control group of animals received one i.p. injection of saline at the dose of 1 ml/kg body weight at the same time. Only sham surgery was performed in the third group of animals. Rats with EPO pretreatment before the experimental lesion exhibited significantly better motor and cognitive function then those with saline injection. No significant changes in the motor and cognitive function were found in the third group of rats (sham operated controls.

  16. Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds

    Directory of Open Access Journals (Sweden)

    Xianhua Zhang

    2017-07-01

    Full Text Available Previously, we only apply a traditional Chinese medicine (TCM Danshen-Chuanxiong-Honghua (DCH for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO. We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS, we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg and FA (100 mg/kg improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds.

  17. Salvia miltiorrhiza Bunge (Danshen) extract attenuates permanent cerebral ischemia through inhibiting platelet activation in rats.

    Science.gov (United States)

    Fei, Yu-Xiang; Wang, Si-Qi; Yang, Li-Jian; Qiu, Yan-Ying; Li, Yi-Ze; Liu, Wen-Yuan; Xi, Tao; Fang, Wei-Rong; Li, Yun-Man

    2017-07-31

    Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO 2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis. The present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism. Following induction of cerebral ischemia in rats by permanent middle cerebral artery occlusion (pMCAO). Neurological defect score, cerebral blood flow, infarct size, and brain edema were measured to evaluate the injury. Arteriovenous shunt thrombosis model and adenosine 5'-diphosphate (ADP) induced acute pulmonary embolism model were conducted to estimate the antithrombotic effect of SCED. In order to investigate the effects of SCED on platelet aggregation, rat platelet-rich-plasma (PRP) were incubated with SCED prior to the addition of the stimuli (ADP or 9, 11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619)). Aggregation was monitored in a light transmission aggregometer. Inhibitory effect of SCED on thromboxane A2 (TXA 2 ) release was detected by ELISA kit. Phospholipase C (PLC)/ Protein kinase C (PKC) signaling pathway was analyzed by a Western blot technique. The effect of the SCED was also studied in vivo on bleeding time in mice. SCED improved the neurological defect score, increased cerebral blood flow, reduced infarct size and alleviated brain edema in rats exposed to pMCAO. After administration of SCED, thrombosis formation in arteriovenous shunt was inhibited and recovery time in pulmonary embolism was shortened. The inhibitory effect of SCED on platelet activation was further confirmed by TXB 2 ELISA kit and Western blot analysis of PLC

  18. [Effect of Scalp-acupuncture Stimulation on Neurological Function and Expression of ASIC 1 a and ASIC 2 b of Hippocampal CA 1 Region in Cerebral Ischemia Rats].

    Science.gov (United States)

    Tian, Liang; Wang, Jin-Hai; Zhao, Min; Bao, Ying-Cun; Shang, Jun-Fang; Yan, Qi; Zhang, Zhen-Chang; Du, Xiao-Zheng; Jiang, Hua; Sun, Run-Jie; Yuan, Bo; Zhang, Xing-Hua; Zhang, Ting-Zhuo; Li, Xing-Lan

    2016-10-25

    To observe the influence of scalp-acupuncture on the expression of acid-sensing ion channels (ASICs) 1 a and 2 b of hippocampal CA 1 region in cerebral ischemia (CI) rats, so as to investigate its mechanism underlying improvement of ischemic stroke. Thirty-two male SD rats were randomly allocated to normal control, model, scalp-acupuncture and Amiloride group ( n =8 in each group). The model of focal CI was established by middle cerebral artery occlusion (MCAO). Scalp acupuncture stimulation was applied to bilateral Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), once daily for 7 days. Rats of the Amiloride group were fed with Amiloride solution, twice a day for 7 days, and those of the normal control and model groups were grabbled and fixed in the same way with the acupuncture and Amiloride groups. The neurological deficit score was given according to Longa's method. The expression of hippocampal ASIC 1 a and ASIC 2 b was detected by immunohistochemistry, and the Ca 2+ concentration in the hippocampal tissue assayed using flowing cytometry. After the intervention, the neurological deficit score of both the scalp-acupuncture and Amiloride groups were significantly decreased in comparison with pre-treatment ( P ASIC 1 a and ASIC 2 b in the hippocampal CA 1 region and hip-pocampal Ca 2+ concentration were significantly up-regulated in the model group compared with the normal control group ( P ASIC 1 a and ASIC 2 b expression and Ca 2+ concentration ( P >0.05). Scalp-acupuncture stimulation can improve neurological function in CI rats, which may be related to its effects in suppressing the increased expression of hippocampal ASIC 1 a and ASIC 2 b proteins and in reducing calcium overload in hip-pocampal neurocytes.

  19. Acupuncture inhibits Notch1 and Hes1 protein expression in the basal ganglia of rats with cerebral hemorrhage

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    Wei Zou

    2015-01-01

    Full Text Available Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduction pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups: in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-heparinized blood into the brain. In the acupuncture group, modeled rats had Baihui (DU20 and Qubin (GB7 acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 μg/mL DAPT solution (10 mL infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch1 and Hes1 protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by inhibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.

  20. Protective Effects of Ferulic Acid against Chronic Cerebral Hypoperfusion-Induced Swallowing Dysfunction in Rats

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    Takashi Asano

    2017-03-01

    Full Text Available Ferulic acid (FA, a phenolic phytochemical, has been reported to exert antioxidative and neuroprotective effects. In this study, we investigated the protective effects of FA against the dysfunction of the swallowing reflex induced by ligation of bilateral common carotid arteries (2VO in rats. In 2VO rats, topical administration of water or citric acid to the pharyngolaryngeal region evoked a diminished number of swallowing events with prolonged latency compared to sham-operated control rats. 2VO rats had an increased level of superoxide anion radical, and decreased dopamine and tyrosine hydroxylase enzyme levels in the striatum, suggesting that 2VO augmented cerebral oxidative stress and impaired the striatal dopaminergic system. Furthermore, substance P (SP expression in the laryngopharyngeal mucosa, which is believed to be positively regulated by dopaminergic signaling in the basal ganglia, was decreased in 2VO rats. Oral treatment with FA (30 mg/kg for 3 weeks (from one week before 2VO to two weeks after improved the swallowing reflex and maintained levels of striatal dopamine and laryngopharyngeal SP expression in 2VO rats. These results suggest that FA maintains the swallowing reflex by protecting the dopamine-SP system against ischemia-induced oxidative damage in 2VO rats.

  1. [Mechanism of treatment effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats based on metabolomic approach].

    Science.gov (United States)

    Cao, Hui-Ting; Zhu, Hua-Xu; Zhang, Qi-Chun; Guo, Li-Wei

    2017-06-01

    The metabolic effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats was studied by using metabolomic method. The rat model of ischemia reperfusion injury induced by introduction of transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Ultra high performance liquid chromatography-series four pole time of flight mass spectrometry method(UPLC-Q-TOF/MS), Markerlynx software, and principal component analysis and partial least-squares discriminant analysis were used to analyze the different endogenous metabolites among the urine samples of sham rats, cerebral ischemia model rats, Huanglian groups (HL), Huangqin groups (HQ) and Huanglian-Huangqin herb pairs groups (LQ) was achieved, combined with accurate information about the endogenous metabolites level and secondary fragment ions, retrieval and identification of possible biological markers, metabolic pathway which build in MetPA database. The 20 potential biomarkers were found in the urine of rats with cerebral ischemia, which mainly involved in the neurotransmitter regulation, amino acid metabolism, energy metabolism, lipid metabolism and so on. Those metabolic pathways were disturbed in cerebral ischemia model rats, the principal component analysis showed that the normal and cerebral ischemia model is clearly distinguished, and the compound can be given to the normal state of change after HL, HQ, LQ administration. This study index the interpretation of cerebral ischemia rat metabolism group and mechanism, the embodiment of metabonomics can reflect the physiological and metabolic state, which can better reflect the traditional Chinese medicine as a whole view, system view and the features of multi ingredient synergistic or antagonistic effects. Copyright© by the Chinese Pharmaceutical Association.

  2. Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

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    Najmeh Kabiri

    2016-09-01

    Full Text Available The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99. Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly higher than the Sham group, although right hemispheres in all of the treated groups illustrated higher brain water content than the left ones. Brain anti-oxidant capacity elevated in the ischemic rats treated with Kombucha and in the Sham group. Brain and plasma malondialdehyde concentrations significantly decreased in both of the ischemic groups injected with Kombucha. The findings suggest that Kombucha tea could be useful for the prevention of cerebral damage.

  3. Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats.

    Science.gov (United States)

    Yang, Weichun; Shi, He; Zhang, Jianfen; Shen, Ziyi; Zhou, Guangyu; Hu, Minyu

    2017-01-31

    The present study was designed to investigate the effects of hyperlipidemia on the cerebral lipids, vessels and neurons of rats, and to provide experimental evidence for subsequent intervention. One hundred adult SD rats, half of which were male and half of which were female, were randomly divided into five groups on the basis of serum total cholesterol (TC) levels. Four groups were fed a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) for periods of 1 week, 2 weeks, 3 weeks and 4 weeks, respectively. A control group was included. The levels of serum lipids, cerebral lipids, free fatty acids (FFA), interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), oxidized low density lipoprotein (ox-LDL), A-beta precursor proteins (APP), amyloid beta (Aβ), glial fibrillary acidic protein (GFAP) and tight junction protein Claudin-5 were measured after the experiment. The pathologic changes and apoptosis of the rat brains were evaluated. Compared with the control group, after 1 week of a CCT diet, the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and brain triglycerides had increased by 2.40, 1.29 and 1.75 and 0.3 times, respectively. The serum high density lipoprotein cholesterol (HDL-C) had decreased by 0.74 times (P neurons, had increased (P neurons had increased (P neuronal apoptosis in the rat brains, and they all were negatively correlated with Claudin-5 (P neurons by causing the secretion of TNF-α and IL-1 in the brains of rats. In the metabolic procession, brain tissue was shown to generate FFA that aggravated the biosynthesis of ox-LDL. With the extension of the duration of hyperlipidemia, high levels of cerebral TC and LDL-C were shown to aggravate the deposition of Aβ, induce the secretion of VEGF, reduce the expression of tight

  4. Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools

    DEFF Research Database (Denmark)

    Kelsen, Jesper; Larsen, Marianne; Sørensen, Jens Christian H.

    2010-01-01

    We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats ...

  5. Rat Pial Microvascular Changes During Cerebral Blood Flow Decrease and Recovery: Effects of Cyanidin Administration

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    Teresa Mastantuono

    2018-05-01

    Full Text Available The reactive oxygen species (ROS are known to play a major role in many pathophysiological conditions, such as ischemia and reperfusion injury. The present study was aimed to evaluate the in vivo cyanidin (anthocyanin effects on damages induced by rat pial microvascular hypoperfusion-reperfusion injury by cerebral blood flow decrease (CBFD and subsequent cerebral blood flow recovery (CBFR. In particular, the main purpose was to detect changes in ROS production after cyanidin administration. Rat pial microvasculature was investigated using fluorescence microscopy through a cranial window (closed; Strahler's method was utilized to define the geometric features of pial vessels. ROS production was investigated in vivo by 2′-7′-dichlorofluorescein-diacetate assay and neuronal damage was measured on isolated brain sections by 2,3,5-triphenyltetrazolium chloride staining. After 30 min of CBFD, induced by bilateral common carotid artery occlusion, and 60 min of CBFR, rats showed decrease of arteriolar diameter and capillary perfusion; furthermore, increase in microvascular leakage and leukocyte adhesion was observed. Conversely, cyanidin administration induced dose-related arteriolar dilation, reduction in microvascular permeability as well as leukocyte adhesion when compared to animals subjected to restriction of cerebral blood flow; moreover, capillary perfusion was protected. ROS generation increase and marked neuronal damage were detected in animals subjected to CBFD and CBFR. On the other hand, cyanidin was able to reduce ROS generation and neuronal damage. In conclusion, cyanidin treatment showed dose-related protective effects on rat pial microcirculation during CBFD and subsequent CBFR, inducing arteriolar dilation by nitric oxide release and inhibiting ROS formation, consequently preserving the blood brain barrier integrity.

  6. Investigation of redox status in chronic cerebral hypoperfusion-induced neurodegeneration in rats

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    Anil Kumar Saxena

    2015-06-01

    Full Text Available Aging related reduction in cerebral blood flow (CBF has been linked with neurodegenerative disorders including Alzheimer's disease and dementia. Experimentally, a condition of chronic cerebral hypoperfusion due to reduced CBF can be induced by permanent bilateral occlusion of common carotid arteries (2-vessel occlusion, 2VO in rats. Since oxidative stress, leading to neuronal apoptosis and death, is one of the mechanisms, which is thought to play a significant role in chronic degenerative neurological disorders, the present study was planned to assess the ROS status by measuring the levels of anti-oxidant enzymes that might occur during chronic cerebral hypoperfusion. Antioxidant enzymes namely glutathione peroxidase (GPx, superoxide dismutase (SOD, and catalase were measured in the brain tissue at eight weeks of 2VO induction in rats. Results show significantly elevated levels of GPx, SOD, and catalase enzymes as compared with the control group. It is possible that compensatory rise in antioxidant enzymes occurs in response to increased oxidative stress following ischemic insult.

  7. Neuroprotection of taurine through inhibition of 12/15 lipoxygenase pathway in cerebral ischemia of rats.

    Science.gov (United States)

    Zhang, Zhe; Yu, Rongbo; Cao, Lei

    2017-05-01

    Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. Taurine (Tau), an endogenous substance, possesses a number of cytoprotective properties. The aim of the present study was to examine the neuroprotective effect of Tau, through affecting 12/15 lipoxygenase (12/15-LOX) signal pathway in an acute permanent middle cerebral artery occlusion (MCAO) model of rats. Sprague-Dawley rats were randomly divided into 3 groups (n = 10), namely the sham-operated group, MCAO group and Tau group. Tau was intraperitoneally administrated immediately after cerebral ischemia. At 24 h after MCAO, neurological function score, brain water content and infarct volume were assessed. The expression of 12/15-lipoxygenase (12/15-LOX), p38 mitogen-activated protein kinase (p38 MAPK), and cytosolic phospholipase A2 (cPLA2) was measured by Western blot. Enzyme-linked immunosorbent assay was used to evaluate the inflammatory factors TNF-α, IL-1β and IL-6 in serum. Compared with MCAO group, taurine significantly improved neurological function and significantly reduced brain water content (p Taurine protected the brain from damage caused by MCAO; this effect may be through down-regulation of 12/15-LOX, p38 MAPK, and cPLA2.

  8. Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat

    Energy Technology Data Exchange (ETDEWEB)

    Mraovitch, S.; Calando, Y.; Goadsby, P.J.; Seylaz, J. (Laboratoire de Recherches Cerebrovasculaire, Paris (France))

    1992-06-01

    Changes in cerebral cortical perfusion (CBF{sub LDF}), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with {alpha}-chloralose. CBF{sub LDF} was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic ({sup 14}C)iodoantipyrine and ({sup 14}C)-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome. 19 refs., 2 figs., 1 tab.

  9. A Microarray Study of Middle Cerebral Occlusion Rat Brain with Acupuncture Intervention

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    Chao Zhang

    2015-01-01

    Full Text Available Microarray analysis was used to investigate the changes of gene expression of ischemic stroke and acupuncture intervention in middle cerebral artery occlusion (MCAo rat brain. Results showed that acupuncture intervention had a remarkable improvement in neural deficit score, cerebral blood flow, and cerebral infarction volume of MCAo rats. Microarray analysis showed that a total of 627 different expression genes were regulated in ischemic stroke. 417 genes were upregulated and 210 genes were downregulated. A total of 361 different expression genes were regulated after acupuncture intervention. Three genes were upregulated and 358 genes were downregulated. The expression of novel genes after acupuncture intervention, including Tph1 and Olr883, was further analyzed by Real-Time Quantitative Polymerase Chain Reaction (RT-PCR. Upregulation of Tph1 and downregulation of Olr883 indicated that the therapeutic effect of acupuncture for ischemic stroke may be closely related to the suppression of poststroke depression and regulation of olfactory transduction. In conclusion, the present study may enrich our understanding of the multiple pathological process of ischemic brain injury and indicate possible mechanisms of acupuncture on ischemic stroke.

  10. A Promising Approach to Integrally Evaluate the Disease Outcome of Cerebral Ischemic Rats Based on Multiple-Biomarker Crosstalk

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    Guimei Ran

    2017-01-01

    Full Text Available Purpose. The study was designed to evaluate the disease outcome based on multiple biomarkers related to cerebral ischemia. Methods. Rats were randomly divided into sham, permanent middle cerebral artery occlusion, and edaravone-treated groups. Cerebral ischemia was induced by permanent middle cerebral artery occlusion surgery in rats. To form a simplified crosstalk network, the related multiple biomarkers were chosen as S100β, HIF-1α, IL-1β, PGI2, TXA2, and GSH-Px. The levels or activities of these biomarkers in plasma were detected before and after ischemia. Concurrently, neurological deficit scores and cerebral infarct volumes were assessed. Based on a mathematic model, network balance maps and three integral disruption parameters (k, φ, and u of the simplified crosstalk network were achieved. Results. The levels or activities of the related biomarkers and neurological deficit scores were significantly impacted by cerebral ischemia. The balance maps intuitively displayed the network disruption, and the integral disruption parameters quantitatively depicted the disruption state of the simplified network after cerebral ischemia. The integral disruption parameter u values correlated significantly with neurological deficit scores and infarct volumes. Conclusion. Our results indicate that the approach based on crosstalk network may provide a new promising way to integrally evaluate the outcome of cerebral ischemia.

  11. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity.

    Science.gov (United States)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats.

    Science.gov (United States)

    Besio, W G; Makeyev, O; Medvedev, A; Gale, K

    2013-07-01

    To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. In the case of the TFS treated group, after TFS, there was a significant (p=0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p=0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p=0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced toward the "baseline." The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

    Science.gov (United States)

    Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

    2017-01-01

    Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

  14. Chronic transcranial focal stimulation from tripolar concentric ring electrodes does not disrupt memory formation in rats.

    Science.gov (United States)

    Luby, Matthew D; Makeyev, Oleksandr; Besio, Walter G

    2014-01-01

    Non-invasive electrical brain stimulation has shown potential utility as a treatment for seizures in epilepsy patients. Transcranial focal stimulation (TFS) via tripolar concentric ring electrodes (TCREs) has been effective in reducing seizure severity in acute rodent models, but it has yet to be determined whether or not it will serve as a viable long-term treatment strategy. Prior experiments indicate that a single dose of TFS via TCRE does not impact short- or long-term memory formation. The present study investigated if five daily doses of TFS via a TCRE on the scalp affected the memory. The spontaneous object recognition (SOR) test was used to evaluate the memory. Sham and TFS-treated groups were evaluated and both showed comparable levels of preference for novel objects, indicating successful memory formation. More work on repeated dosage strategies is important for establishing the safety and efficacy of TFS as a putative treatment.

  15. Levetiracetam Affects Differentially Presynaptic Proteins in Rat Cerebral Cortex

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    Daniele Marcotulli

    2017-12-01

    Full Text Available Presynaptic proteins are potential therapeutic targets for epilepsy and other neurological diseases. We tested the hypothesis that chronic treatment with the SV2A ligand levetiracetam affects the expression of other presynaptic proteins. Results showed that in rat neocortex no significant difference was detected in SV2A protein levels in levetiracetam treated animals compared to controls, whereas levetiracetam post-transcriptionally decreased several vesicular proteins and increased LRRK2, without any change in mRNA levels. Analysis of SV2A interactome indicates that the presynaptic proteins regulation induced by levetiracetam reported here is mediated by this interactome, and suggests that LRRK2 plays a role in forging the pattern of effects.

  16. Impaired cerebral microcirculation induced by ammonium chloride in rats is due to cortical adenosine release

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Bjerrum, Esben Jannik; Larsen, Fin Stolze

    2018-01-01

    BACKGROUND: Liver failure results in hyperammonaemia, impaired regulation of cerebral microcirculation, encephalopathy and death. However, the key mediator that alters cerebral microcirculation remains unidentified. In this study we show that topical ammonium significantly increases periarteriolar......: In patients with liver failure disturbances in the brain function is caused in part by ammonia toxicity. In our project we have studied how ammonia, through adenosine release, affects the blood flow in the brain of rats. In our experimental model we demonstrated that the detrimental effect of ammonia on blood...... flow regulation was counteracted by blocking the adenosine receptors in the brain. With this observation we have identified a novel potential treatment target. If we can confirm our findings in a future clinical study it might help patients suffering from liver failure and the severe condition called...

  17. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus

    Science.gov (United States)

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions. PMID:25317156

  18. Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation.

    Science.gov (United States)

    Huang, Y C; Tzeng, W S; Wang, C C; Cheng, B C; Chang, Y K; Chen, H H; Lin, P C; Huang, T Y; Chuang, T J; Lin, J W; Chang, C P

    2013-09-01

    This study aimed to further investigate the effects of agmatine on brain edema in the rats with middle cerebral artery occlusion (MCAO) injury using magnetic resonance imaging (MRI) monitoring and biochemical and histopathologic evaluation. Following surgical induction of MCAO for 90min, agmatine was injected 5min after beginning of reperfusion and again once daily for the next 3 post-operative days. The events during ischemia and reperfusion were investigated by T2-weighted images (T2WI), serial diffusion-weighted images (DWI), calculated apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted images (CE-T1WI) during 3h-72h in a 1.5T Siemens MAGNETON Avanto Scanner. Lesion volumes were analyzed in a blinded and randomized manner. Triphenyltetrazolium chloride (TTC), Nissl, and Evans Blue stainings were performed at the corresponding sections. Increased lesion volumes derived from T2WI, DWI, ADC, CE-T1WI, and TTC all were noted at 3h and peaked at 24h-48h after MCAO injury. TTC-derived infarct volumes were not significantly different from the T2WI, DWI-, and CE-T1WI-derived lesion volumes at the last imaging time (72h) point except for significantly smaller ADC lesions in the MCAO model (Pagmatine-treated rats compared with the control ischemia rats (Pagmatine has neuroprotective effects against brain edema on a reperfusion model after transient cerebral ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Use of hypoxia imaging agent 99mTc-HL91 in rat cerebral ischemia models

    International Nuclear Information System (INIS)

    Zhou Ying; Qu Wanying; Li Meng; Chen Fang; Yao Zhiming; Zhu Ming; Zhu Lin

    1999-01-01

    Objective: To explore the possibility of diagnosis for cerebrovascular disease by a novel synthetic hypoxia agent 99m Tc-HL91 used in rat cerebral ischemia models. Methods: Pharmacological experiments of 99m Tc-HL91 were carried out including common properties, radiochemical purity, stability in vitro, anomalous toxicity test and biodistribution in mice. Fifteen cerebral ischemic rat models were established and received 99m Tc-HL91 scintigraphy. Results: 1) HL91 kits were labelled with 99m Tc easily and showed high radiochemical purity and stability. 2) Rapid clearance in blood, heart and lungs and high activity in liver, kidneys and intestines were observed. Relatively low uptake in brain was identified. 3) The radioactivity in ischemic brain tissue increased significantly at 4h postinjection in both rat images and isolated brain images. 4) The radioactivity ratios of lesion to normal brain tissue by drawing ROIs in isolated brain planar images were 0.98 +- 0.06, 0.99 +- 0.05, 1.29 +- 0.03, 1.56 +- 0.14 and 1.66 +- 0.06 at 1,2,4,8 and 12 h postinjection, respectively. There were significant differences among all groups except for 1 h and 2 h, 8 h and 12 h postinjection (P 99m Tc-HL91 in the hypoxic, ischemic brain tissue have been proved. It is appropriate to perform imaging at 4 h postinjection

  20. Particular phosphorylation of PI3K/Akt on Thr308 via PDK-1 and PTEN mediates melatonin's neuroprotective activity after focal cerebral ischemia in mice

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    Ulkan Kilic

    2017-08-01

    Full Text Available Apart from its potent antioxidant property, recent studies have revealed that melatonin promotes PI3K/Akt phosphorylation following focal cerebral ischemia (FCI in mice. However, it is not clear (i whether increased PI3K/Akt phosphorylation is a concomitant event or it directly contributes to melatonin's neuroprotective effect, and (ii how melatonin regulates PI3K/Akt signaling pathway after FCI. In this study, we showed that Akt was intensively phosphorylated at the Thr308 activation loop as compared with Ser473 by melatonin after FCI. Melatonin treatment reduced infarct volume, which was reversed by PI3K/Akt inhibition. However, PI3K/Akt inhibition did not inhibit melatonin's positive effect on brain swelling and IgG extravasation. Additionally, phosphorylation of mTOR, PTEN, AMPKα, PDK1 and RSK1 were increased, while phosphorylation of 4E-BP1, GSK-3α/β, S6 ribosomal protein were decreased in melatonin treated animals. In addition, melatonin decreased apoptosis through reduced p53 phosphorylation by the PI3K/Akt pathway. In conclusion, we demonstrated the activation profiles of PI3K/Akt signaling pathway components in the pathophysiological aspect of ischemic stroke and melatonin's neuroprotective activity. Our data suggest that Akt phosphorylation, preferably at the Thr308 site of the activation loop via PDK1 and PTEN, mediates melatonin's neuroprotective activity and increased Akt phosphorylation leads to reduced apoptosis. Keywords: PI3K/Akt signaling pathway, PI3K inhibition, Melatonin, Brain injury

  1. Niosomes of Ascorbic Acid and α-Tocopherol in the Cerebral Ischemia-Reperfusion Model in Male Rats

    OpenAIRE

    Varshosaz, Jaleh; Taymouri, Somayeh; Pardakhty, Abbas; Asadi-Shekaari, Majid; Babaee, Abodolreza

    2014-01-01

    The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neur...

  2. The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat

    DEFF Research Database (Denmark)

    Maddahi, Aida; Kruse, Lars S; Chen, Qing-Wen

    2011-01-01

    Tumour necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-α acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expre...... expression of TNF-α and TNF-α receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway....

  3. The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat

    DEFF Research Database (Denmark)

    Maddahi, Aida; Kruse, Lars S; Chen, Qing-Wen

    2011-01-01

    Tumour necrosis factor-a (TNF-a) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-a acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expre...... expression of TNF-a and TNF-a receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway....

  4. A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow autoregulation after subarachnoid haemorrhage in rats

    DEFF Research Database (Denmark)

    Springborg, Jacob Bertram; Ma, XiaoDong; Rochat, Per

    2002-01-01

    the intracarotid (133)Xe method. CBF autoregulation was preserved in both sham-operated groups (lower limits of mean arterial blood pressure: 91+/-3 and 98+/-3 mmHg in groups A and B, respectively). In the vehicle treated SAH-group, autoregulation was abolished and the relationship between CBF and blood pressure...... administered recombinant EPO on impaired cerebral blood flow (CBF) autoregulation after experimental subarachnoid haemorrhage (SAH). Four groups of male Sprague-Dawley rats were studied: group A, sham operation plus vehicle; group B, sham operation plus EPO; group C, SAH plus vehicle; group D, SAH plus EPO...

  5. Effect of. beta. -endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-10-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus.

  6. Effect of β-endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    International Nuclear Information System (INIS)

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-01-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus

  7. Enhanced cerebrovascular expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 via the MEK/ERK pathway during cerebral ischemia in the rat

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    Maddahi Aida

    2009-06-01

    Full Text Available Abstract Background Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression of metalloproteinase-9 (MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1. Results Here, we found an infarct volume of 24.8 ± 2% and a reduced neurological function after two hours of middle cerebral artery occlusion (MCAO, followed by 48 hours of recirculation in rat. Immunocytochemistry and confocal microscopy revealed enhanced expression of MMP-9, TIMP-1, and phosphorylated ERK1/2 in the smooth muscle cells of the ischemic MCA and associated intracerebral microvessels. The specific MEK1/2 inhibitor U0126, given intraperitoneal zero or 6 hours after the ischemic event, reduced the infarct volume significantly (11.8 ± 2% and 14.6 ± 3%, respectively; P Conclusion These data are the first to show that the elevated vascular expression of MMP-9 and TIMP-1, associated with breakdown of the blood-brain barrier following focal ischemia, are transcriptionally regulated via the MEK/ERK pathway.

  8. rLj-RGD3, a Novel Recombinant Toxin Protein from Lampetra japonica, Protects against Cerebral Reperfusion Injury Following Middle Cerebral Artery Occlusion Involving the Integrin-PI3K/Akt Pathway in Rats.

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    Qian Lu

    Full Text Available The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3 and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO in a rat stroke model. We also explored the mechanism by which rLj-RGD3 acts by measuring protein and mRNA expression levels, with an emphasis on the FAK and integrin-PI3K/Akt anti-apoptosis pathways.rLj-RGD3 was obtained from the buccal secretions of Lampetra japonica using gene recombination technology. Sprague Dawley (SD rats were randomly divided into the following seven groups: a sham group; a vehicle-treated (VT group; 100.0 μg·kg-1, 50.0 μg·kg-1 and 25.0 μg·kg-1 dose rLj-RGD3 groups; and two positive controls, including 1.5 mg·kg-1 Edaravone (ED and 100.0 μg·kg-1 Eptifibatide (EP. MCAO was induced using a model consisting of 2 h of ischemia and 24 h of reperfusion. Behavioral changes were observed in the normal and operation groups after focal cerebral ischemia/reperfusion was applied. In addition, behavioral scores were evaluated at 4 and 24 h after reperfusion. Brain infarct volumes were determined based on 2,3,5-triphenyltetrazolium chloride (TTC staining. Pathological changes in brain tissues were observed using hematoxylin and eosin (H&E staining. Moreover, neuronal apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL assays. We determined the expression levels of focal adhesion kinase (FAK, phosphatidyl inositol 3-kinase (PI3K, protein kinase B

  9. Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats

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    Juan P. Hernández-Fonseca

    2009-01-01

    Full Text Available Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral.

  10. The cholinergic-inducing effect of BMP4 on rat's cerebral neural stem cells

    International Nuclear Information System (INIS)

    Chang Yan; Xue Yilong; Luo Yun; Tian Lei; Pan Jingkun; Cui Xin

    2004-01-01

    The cholinergic-inducing effect of BMP4 on isolated and cultivated rat's cerebral neural stem cells (NSC) was examined. NSC isolated from two months old rat's brain region like hippocampus and striatum was cultivated in a DMEM/F12 medium containing EGF and bFGF, and was identified with morphological character and nestin immunocytochemistry test. After 24 hours, cultivating the NSC with the BMP4-added medium for 7-8 days, then the microscopical change were observed, ChAT and nestin double-labelling immunocytochemistry test was done. Results showed that about 34% NSC of neuron-like character was observed by microscope in the paper. That ChAT-positive cells coexist with nestin-positive cells was found by immunocytochemistry test. There were 28% ChAT-positive cells and 38% nestin-positive cells in the study. Cholinergic neurons differentiated from NSC could be induced by adding BMP4 to the medium

  11. Functional response of cerebral blood flow induced by somatosensory stimulation in rats with subarachnoid hemorrhage

    Science.gov (United States)

    Li, Zhiguo; Huang, Qin; Liu, Peng; Li, Pengcheng; Ma, Lianting; Lu, Jinling

    2015-09-01

    Subarachnoid hemorrhage (SAH) is often accompanied by cerebral vasospasm (CVS), which is the phenomenon of narrowing of large cerebral arteries, and then can produce delayed ischemic neurological deficit (DIND) such as lateralized sensory dysfunction. CVS was regarded as a major contributor to DIND in patients with SAH. However, therapy for preventing vasospasm after SAH to improve the outcomes may not work all the time. It is important to find answers to the relationship between CVS and DIND after SAH. How local cerebral blood flow (CBF) is regulated during functional activation after SAH still remains poorly understood, whereas, the regulation of CBF may play an important role in weakening the impact of CVS on cortex function. Therefore, it is worthwhile to evaluate the functional response of CBF in the activated cortex in an SAH animal model. Most evaluation of the effect of SAH is presently carried out by neurological behavioral scales. The functional imaging of cortical activation during sensory stimulation may help to reflect the function of the somatosensory cortex more locally than the behavioral scales do. We investigated the functional response of CBF in the somatosensory cortex induced by an electrical stimulation to contralateral forepaw via laser speckle imaging in a rat SAH model. Nineteen Sprague-Dawley rats from two groups (control group, n=10 and SAH group, n=9) were studied. SAH was induced in rats by double injection of autologous blood into the cisterna magna after CSF aspiration. The same surgical procedure was applied in the control group without CSF aspiration or blood injection. Significant CVS was found in the SAH group. Meanwhile, we observed a delayed peak of CBF response in rats with SAH compared with those in the control group, whereas no significant difference was found in magnitude, duration, and areas under curve of relative CBF changes between the two groups. The results suggest that the regulation function of local CBF during

  12. Neuroprotective effect of TAT-14-3-3ε fusion protein against cerebral ischemia/reperfusion injury in rats.

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    Yuanjun Zhu

    Full Text Available Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB due to its large size. A protein transduction domain (PTD of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP, which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic

  13. Cerebral blood flow, glucose use, and CSF ionic regulation in potassium-depleted rats

    International Nuclear Information System (INIS)

    Schroek, H.; Kuschinsky, W.

    1988-01-01

    Rats were kept on a low-K + diet for 25 or 70 days. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 31 different structures of the brain by means of the [ 14 C]iodoantipyrine and [ 14 C]2-deoxy-D-glucose method. After 25 and 70 days of K + depletion LCBF was decreased significantly in 27 and 30 structures, respectively, the average decrease being 19 and 25%. In contrast, average LCGU was not changed. Cisternal cerebrospinal fluid (CSF) K + concentration decreased significantly from 2.65 ± 0.02 mM in controls to 2.55 ± 0.02 mM and 2.47 ± 0.02 mM in the two treated groups. CSF [HCO 3 - ], pH, and Pco 2 were increased in K + -depleted animals. These data show that K + depletion induces an increase in CSF pH and a decrease in CSF K + concentration, both of which cause a reduction in cerebral blood flow. The increased CSF Pco 2 is secondary to the reduction of blood flow, since brain metabolism and arterial Pco 2 remained constant

  14. MRI in acute cerebral ischaemia: perfusion imaging with superparamagnetic iron oxide in a rat model

    International Nuclear Information System (INIS)

    Forsting, M.; Reith, W.; Doerfler, A.; Kummer, R. von; Hacke, W.; Sartor, K.

    1994-01-01

    An imaging technique capable of detecting ischaemic cerebral injury at an early stage could improve diagnosis in acute or transient cerebral ischaemia. We compared the ability of superparamagnetically contrast-enhanced MRI and conventional T2-weighted MRI to detect ischaemic injury early after unilateral occlusion of the middle cerebral artery in 12 male Wistar rats. Permanent vessel occlusion was achieved by a transvascular approach, which has the advantage of not requiring a craniectom. At 45-60 min after the procedure, the animals had conventional T2-weighted MRI before and after administration of a superparamagnetic contrast agent (iron oxide particles). Unenhanced images were normal in all animals. After administration of iron oxide particles, the presumed ischaemic area was clearly visible, as relatively increased signal, in all animals; this high signal area corresponded to the area of ischaemic brain infarction seen on histological studies. Our results suggest that superparamagnetic iron particles may significantly reduce the interval between an ischaemic insult and the appearance of parenchymal changes on MRI. (orig./UWA)

  15. Early polymorphonuclear leukocyte accumulation correlates with the development of posttraumatic cerebral edema in rats

    International Nuclear Information System (INIS)

    Schoettle, R.J.; Kochanek, P.M.; Magargee, M.J.; Uhl, M.W.; Nemoto, E.M.

    1990-01-01

    To evaluate the role of polymorphonuclear leukocytes (PMNs) in the development of posttraumatic cerebral edema, we quantitatively assessed the time course and magnitude of PMN accumulation and its relationship to cerebral edema formation after cerebral trauma in 78 rats. 111 In-labeled PMN accumulation was measured in 26 rats in the first 8 h after right hemispheric percussive cerebral trauma or a sham control condition. 51 Cr-labeled erythrocyte accumulation was measured simultaneously in 22 rats to assess the contribution of expansion of blood volume to early posttraumatic PMN accumulation. Edema formation [right-left (R-L) hemispheric difference in percent brain water], R-L hemispheric labeled-PMN accumulation, and blood volume index-adjusted PMN accumulation were measured between 0-2 h and 4-8 h posttrauma. PMN accumulation was elevated markedly in the first 2 h posttrauma compared with values in sham controls (13.45 +/- 2.53 vs -0.03 +/- 0.31, p less than 0.01) but not when adjusted for blood volume index (BVI), suggesting that PMN accumulation in the first 2 h posttrauma was due to expansion of blood volume. Between 4 and 8 h posttrauma, however, both total (2.56 +/- 0.82 vs -0.29 +/- 0.52) and BVI-adjusted (8.78 +/- 3.97 vs -0.48 +/- 0.79) PMN accumulation were elevated (p less than 0.05) compared with sham. Brain edema and total PMN accumulation were significantly correlated at both 2 h and 8 h posttrauma (r2 = 0.77, p less than 0.001, and r2 = 0.69, p less than 0.002, respectively), but a significant correlation between edema and BVI-adjusted PMN accumulation was observed only at 8 h posttrauma (r2 = 0.96, p less than 0.001). These data show that PMN accumulation after traumatic brain injury occurs with an initial phase explained by an increase in blood volume in the first 2 h posttrauma followed by a subsequent acute inflammatory phase

  16. Toward a noninvasive automatic seizure control system in rats with transcranial focal stimulations via tripolar concentric ring electrodes.

    Science.gov (United States)

    Makeyev, Oleksandr; Liu, Xiang; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Mucio-Ramirez, Samuel; Liu, Yuhong; Sun, Yan L; Kay, Steven M; Besio, Walter G

    2012-07-01

    Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study, we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback.

  17. Neuroprotective effects of SMADs in a rat model of cerebral ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Fang-fang Liu

    2015-01-01

    Full Text Available Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.

  18. Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model

    International Nuclear Information System (INIS)

    Toyama, Hiroshi; Takeuchi, Akira; Koga, Sukehiko; Matsumura, Kaname; Nakashima, Hiromichi; Takeda, Kan; Yoshida, Toshimichi; Ichise, Masanori

    1998-01-01

    I-123-iomazenil is a SPECT probe for central benzodiazepine receptors (BZR) which may reflect intact cortical neuron density after ischemic insults. We evaluated whether neuronal damage in rats could be characterized by iomazenil as compared with cerebral blood flow (CBF). Serial changes in I-125-iomazenil for BZR and I-123-IMP for CBF were analyzed after the unilateral middle cerebral artery occlusion in rats by using an in vivo dualtracer technique. Uptake ratios of affected to contralateral regions were calculated. The iomazenil as well as IMP were decreased in all regions except for the cerebellum (remote area). Both iomazenil and IMP increased over time except in the temporal region (ischemic core). The iomazenil uptake was higher than IMP except in the ischemic core between 1 and 3-4 wk when iomazenil was lower than IMP. Iomazenil showed a moderate decrease in the proximal and middle parietal regions (peri-infarct areas) at 3-4 wk. The triphenyl-tetrazolium-chloride (TTC) stain at 1 wk demonstrated unstained tissue in the temporal region indicating tissue necrosis. With hematoxylin-eosin (HE) stain at 1 wk, widespread neuronal necrosis with occasional intact neurons were found in the proximal parietal region, and isolated necrotic neurons were represented in the distal parietal region. Iomazenil correlated well with the neuron distribution and the finding of a discrepancy between iomazenil and IMP might be useful in evaluating the neuronal damage. (author)

  19. Asymmetry in the brain influenced the neurological deficits and infarction volume following the middle cerebral artery occlusion in rats

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    Zhang Meizeng

    2008-12-01

    Full Text Available Abstract Background Paw preference in rats is similar to human handedness, which may result from dominant hemisphere of rat brain. However, given that lateralization is the uniqueness of the humans, many researchers neglect the differences between the left and right hemispheres when selecting the middle cerebral artery occlusion (MCAO in rats. The aim of this study was to evaluate the effect of ischemia in the dominant hemisphere on neurobehavioral function and on the cerebral infarction volume following MCAO in rats. Methods The right-handed male Sprague-Dawley rats asserted by the quadrupedal food-reaching test were subjected to 2 hours MCA occlusion and then reperfusion. Results The neurological scores were significantly worse in the left MCAO group than that in the right MCAO group at 1 h, 24 h, 48 h and 72 h (p 0.05 respectively. There was a trend toward better neurobehavioral function recovery in the right MCAO group than in the left MCAO group. The total infarct volume in left MCAO was significantly larger than that in the right (p Conclusion The neurobehavioral function result and the pathological result were consistent with the hypothesis that paw preference in rats is similar to human handedness, and suggested that ischemia in dominant hemisphere caused more significant neurobehavioral consequence than in another hemisphere following MCAO in adult rats. Asymmetry in rat brain should be considered other than being neglected in choice of rat MCAO model.

  20. Bexarotene reduces blood-brain barrier permeability in cerebral ischemia-reperfusion injured rats.

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    Lu Xu

    Full Text Available Matrix metalloproteinase-9 (MMP-9 over-expression disrupts the blood-brain barrier (BBB in the ischemic brain. The retinoid X receptor agonist bexarotene suppresses MMP-9 expression in endothelial cells and displays neuroprotective effects. Therefore, we hypothesized that bexarotene may have a beneficial effect on I/R-induced BBB dysfunction.A total of 180 rats were randomized into three groups (n = 60 each: (i a sham-operation group, (ii a cerebral ischemia-reperfusion (I/R group, and (iii an I/R+bexarotene group. Brain water content was measured by the dry wet weight method. BBB permeability was analyzed by Evans Blue staining and the magnetic resonance imaging contrast agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were assessed by reverse transcription polymerase chain reaction, Western blotting, and gelatin zymography, respectively. Apolipoprotein E (apoE, claudin-5, and occludin expression were analyzed by Western blotting.After 24 h, 48 h, and 72 h post-I/R, several effects were observed with bexarotene administration: (i brain water content and BBB permeability were significantly reduced; (ii MMP-9 mRNA and protein expression as well as activity were significantly decreased; (iii claudin-5 and occludin expression were significantly increased; and (iv apoE expression was significantly increased.Bexarotene decreases BBB permeability in rats with cerebral I/R injury. This effect may be due in part to bexarotene's upregulation of apoE expression, which has been previously shown to reduce BBB permeability through suppressing MMP-9-mediated degradation of the tight junction proteins claudin-5 and occludin. This work offers insight to aid future development of therapeutic agents for cerebral I/R injury in human patients.

  1. Study of the influence and molecular mechanism of ticagrelor on cerebral ischemia reperfusion injury in rats

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    Gui-Fa Chen

    2017-06-01

    Full Text Available Objective: To study the influence and molecular mechanism of ticagrelor on cerebral ischemia reperfusion injury in rats. Methods: SD rats were selected as experimental animals and divided into control group, model group, ticagrelor group and clopidogrel group, cerebral ischemic reperfusion injury models were made, then ticagrelor group were given intragastric administration of 150 mg ticagrelor, clopidogrel group were given intragastric administration of 90 mg clopidogrel. 1 week after intervention, the brain water content as well as the contents of oxidative stress molecules and inflammatory factors were measured. Results: Water content in brain, MDA, Ox-LDL, NF-kB, TNF-α, IL-1β and IL-6 contents in brain tissue as well as TNF-α, IL-1β and IL-6 contents in serum of model group were significantly higher than those of control group while SOD, GSH-Px and Prdx6 contents in brain tissue were significantly lower than those of control group; water content in brain, MDA, Ox-LDL, NFkB, TNF-α, IL-1β and IL-6 contents in brain tissue as well as TNF-α, IL-1β and IL-6 contents in serum of ticagrelor group and clopidogrel group were significantly lower than those of model group while SOD, GSH-Px and Prdx6 contents in brain tissue were significantly higher than those of model group; water content in brain, MDA, Ox-LDL, NF-kB, TNF-α, IL-1β and IL-6 contents in brain tissue as well as TNF-α, IL-1β and IL-6 contents in serum of ticagrelor group were significantly lower than those of clopidogrel group while SOD, GSHPx and Prdx6 contents in brain tissue were significantly higher than those of clopidogrel group. Conclusion: Ticagrelor can be more effective in inhibiting oxidative stress response and inflammatory response, and reducing the cerebral ischemia reperfusion injury than clopidogrel.

  2. Cytofluorometric analysis of proliferation kinetics of cerebral cells of prenatally irradiated rats

    International Nuclear Information System (INIS)

    Borovitskaya, A.E.; Evtushenko, V.I.; Tokalov, S.V.; Yagunov, A.S.; Khanson, K.P.

    1994-01-01

    Prenatal irradiation of humans or animals causes serious and life-long functional and structural damage to the central nervous system. Irradiation of a fetus decreases its brain mass, an effect accompanied by a broad spectrum of disorders in higher nervous activity and behavior. The extent of cerebral damage depends on the kind of radiation, dosage, and on the stage of embryonic development. In rodents, the most serious damage resulted from the irradiation of 15-18 day embryos. Prenatally irradiated animals had pronounced morphological and biochemical changes within the brain, as well as serious deviations from normal behavior. The cerebral structural-functional disorders are known to result from the destruction of irradiated cells, primarily of neuroblasts. The authors used flow cytofluorometry to study the proliferation of cerebral cells at various ontogenetic stages in rats antenatally exposed to γ-neutron radiation. For one-week old animals, the postradiation changes of cell distributions over the cell cycle were found only within the cerebellum. This likely reflects the compensatory cell proliferation, because delayed postnatal development is typical of this part of the brain. There were no detectable differences in brain cytokinetics between two week-old control and irradiated animals. Most of the brain cells (except a limited population of glia, endothelial cells, and cells of the secondary germinal layer) are in the resting state during this period, and radiation does not change their cell cycle distributions. Thus, the increasing occurrence of the S + G 2 + M phases in the cell cycle observed in newborn irradiated rats may reflect the enhanced proliferation of nervous cells surviving the irradiation. However, this compensatory proliferation does not prevent the brain mass from being deficient in the postnatal development of prenatally irradiated animals

  3. Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

    Science.gov (United States)

    Villa, R F; Ferrari, F; Gorini, A

    2012-12-27

    Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

  4. Protective effects of D-Limonene against transient cerebral ischemia in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Wang, Xifeng; Li, Gang; Shen, Wei

    2018-01-01

    Stroke is a leading cause of disability and death world-wide and there is currently a lack of effective treatments for acute stroke. D-Limonene is a common natural monocyclic monoterpene possessing various activities. The present study aimed to evaluate the therapeutic efficacy of D-limonene against ischemia-associated cerebral injury in hypertensive SHRsp rats. Although systolic blood pressure was not altered by ischemia, D-Limonene decreased the systolic blood pressure of SHRsp rats following stroke. Induction of stroke resulted in increased escape latency time, decreased time spent in the target quadrant in the probe trial, decreased capacity to distinguish between familiar objects and novel objects, and increased sensory neglect in the SHRsp rat, however these symptoms were significantly inhibited by D-limonene. D-limonene also decreased the cerebral infarct size in the SHRsp rats following stroke. D-Limonene markedly decreased the mRNA expression of interleukin-1β, monocyte chemoattractant protein-1 and cyclooxygenase-2 in SHRsp rats following stroke. The mRNA expression of vascular endothelial growth factor in the brain of SHRsp rats following stroke was significantly increased by D-Limonene. D-Limonene increased the activities of superoxide dismutase and catalase, decreased the malondialdehyde level, increased glutathione content and reduced the DHE-staining in SHRsp rats following stroke. Overall, inhibition of cerebral inflammation, vascular remodeling and antioxidant activities of D-Limonene may be involved in the protective effects against ischemia-induced damage in SHRsp rats. The present study identified D-Limonene as a potential therapeutic candidate for treatment of stroke-associated cerebral and vascular damage under conditions of hypertension.

  5. The effects of apomorphine upon local cerebral glucose utilization in conscious rats and in rats anesthetized with chloral hydrate

    Energy Technology Data Exchange (ETDEWEB)

    Grome, J J; McCulloch, J

    1983-02-01

    The effects of the dopaminergic agonist apomorphine (1 mg . kg-1 i.v.) upon local cerebral glucose utilization in 43 anatomically discrete regions of the CNS were examined in conscious, lightly restrained rats and in rats anesthetized with chloral hydrate by means of the quantitative autoradiographic (/sup 14/C)2-deoxyglucose technique. In animals anesthetized with chloral hydrate, glucose utilization was reduced throughout all regions of the CNS from the levels observed in conscious animals, although the magnitude of the reductions in glucose use displayed considerable regional heterogeneity. With chloral hydrate anesthesia, the proportionately most marked reductions in glucose use (by 40-60% from conscious levels) were noted in primary auditory nuclei, thalmaic relay nuclei, and neocortex, and the least pronounced reductions in glucose use (by 15-25% from conscious levels) were observed in limbic areas, some motor relay nuclei, and white matter. In conscious, lightly restrained rats, the administration of apomorphine (1 mg . kg-1) effected significant increased in glucose utilization in 15 regions of the CNS (e.g., subthalamic nucleus, ventral thalamic nucleus, rostral neocortex, substantia nigra, pars reticulata), and significant reductions in glucose utilization in two regions of the CNS (lateral habenular nucleus and anterior cingulate cortex).

  6. Daily consumption of white tea (Camellia sinensis (L.)) improves the cerebral cortex metabolic and oxidative profile in prediabetic Wistar rats.

    Science.gov (United States)

    Nunes, Ana R; Alves, Marco G; Tomás, Gonçalo D; Conde, Vanessa R; Cristóvão, Ana C; Moreira, Paula I; Oliveira, Pedro F; Silva, Branca M

    2015-03-14

    Diabetes mellitus (DM) is a major public health problem and its incidence is rising dramatically. The brain, particularly the cerebral cortex, is very susceptible to glucose fluctuations and hyperglycaemia-induced oxidative stress. Tea (Camellia sinensis (L.)) is widely consumed; however, the antidiabetic properties of white tea remain largely unexplored. In the present study, we investigated the effects of daily consumption of white tea on the cerebral cortex of prediabetic rats. The cerebral cortex metabolic profile was evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined. The cerebral cortex oxidative profile was determined by evaluating its antioxidant power, lipid peroxidation and protein oxidation levels. Catalase, glutathione, glutamate, N-acetylaspartate, aspartate, choline, γ-aminobutyric acid, taurine and valine contents were determined. Daily consumption of white tea ameliorated glucose tolerance and insulin sensitivity. Moreover, white tea altered the cortex glycolytic profile, modulating GLUT expression and lactate and alanine contents. Finally, white tea consumption restored protein oxidation and lipid peroxidation levels and catalase expression, and improved antioxidant capacity. In conclusion, daily consumption of white tea improved the cerebral cortex metabolic and oxidative profile in prediabetic rats, suggesting it as a good, safe and inexpensive strategy to prevent DM-related effects in the cerebral cortex.

  7. Microglial involvement in neuroplastic changes following focal brain ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Alexandre Madinier

    2009-12-01

    Full Text Available The pathogenesis of ischemic stroke is a complex sequence of events including inflammatory reaction, for which the microglia appears to be a major cellular contributor. However, whether post-ischemic activation of microglial cells has beneficial or detrimental effects remains to be elucidated, in particular on long term brain plasticity events. The objective of our study was to determine, through modulation of post-stroke inflammatory response, to what extent microglial cells are involved in some specific events of neuronal plasticity, neurite outgrowth and synaptogenesis. Since microglia is a source of neurotrophic factors, the identification of the brain-derived neurophic factor (BDNF as possible molecular actor involved in these events was also attempted. As a means of down-regulating the microglial response induced by ischemia, 3-aminobenzamide (3-AB, 90 mg/kg, i.p. was used to inhibit the poly(ADP-ribose polymerase-1 (PARP-1. Indeed, PARP-1 contributes to the activation of the transcription factor NF-kB, which is essential to the upregulation of proinflammatory genes, in particular responsible for microglial activation/proliferation. Experiments were conducted in rats subjected to photothrombotic ischemia which leads to a strong and early microglial cells activation/proliferation followed by an infiltration of macrophages within the cortical lesion, events evaluated at serial time points up to 1 month post-ictus by immunostaining for OX-42 and ED-1. Our most striking finding was that the decrease in acute microglial activation induced by 3-AB was associated with a long term down-regulation of two neuronal plasticity proteins expression, synaptophysin (marker of synaptogenesis and GAP-43 (marker of neuritogenesis as well as to a significant decrease in tissue BDNF production. Thus, our data argue in favour of a supportive role for microglia in brain neuroplasticity stimulation possibly through BDNF production, suggesting that a targeted

  8. Preventing High Altitude Cerebral Edema in Rats with Repurposed Anti-Angiogenesis Pharmacotherapy.

    Science.gov (United States)

    Tarshis, Samantha; Maltzahn, Joanne; Loomis, Zoe; Irwin, David C

    2016-12-01

    High altitude cerebral edema (HACE) is a fulminant, deadly, and yet still unpredictable brain disease. A new prophylactic treatment for HACE and its predecessor, acute mountain sickness (AMS), needs to be developed without the contraindications or adverse effect profiles of acetazolamide and dexamethasone. Since neovascularization signals are likely key contributors to HACE/AMS, our approach was to examine already existing anti-angiogenic drugs to inhibit potential initiating HACE pathway(s). This approach can also reveal crucial early steps in the frequently debated mechanism of HACE/AMS pathogenesis. We exposed four rat cohorts to hypobaric hypoxia and one to sea level (hyperbaric) conditions. The cohorts were treated with saline controls, an anti-angiogenesis drug (motesanib), a pro-angiogenesis drug (deferoxamine), or an intraperitoneal version of the established AMS prophylaxis drug, acetazolamide (benzolamide). Brain tissue was analyzed for cerebrovascular leak using the Evans Blue Dye (EVBD) protocol. We observed significantly increased EVBD in the altitude control and pro-angiogenesis (deferoxamine) cohorts, and significantly decreased EVBD in the anti-angiogenesis (motesanib), established treatment (benzolamide), and sea-level cohorts. Anti-angiogenesis-treated cohorts demonstrated less cerebrovascular extravasation than the altitude control and pro-angiogenesis treated rats, suggesting promise as an alternative prophylactic HACE/AMS treatment. The leak exacerbation with pro-angiogenesis treatment and improvement with anti-angiogenesis treatment support the hypothesis of early neovascularization signals provoking HACE. We demonstrate statistically significant evidence to guide further investigation for VEGF- and HIF-inhibitors as HACE/AMS prophylaxis, and as elucidators of still unknown HACE pathogenesis.Tarshis S, Maltzahn J, Loomis Z, Irwin DC. Preventing high altitude cerebral edema in rats with repurposed anti-angiogenesis pharmacotherapy. Aerosp Med

  9. Characterization of rat cerebral cortical beta adrenoceptor subtypes using (-)-[125I]-iodocyanopindolol

    International Nuclear Information System (INIS)

    Tiong, A.H.; Richardson, J.S.

    1990-01-01

    (-)-[125I]-Iodocyanopindolol [-(ICYP)], used to characterize beta adrenoceptors on membrane preparations from rat cerebral cortex, was shown to have affinity for both beta adrenoceptors and serotonin receptors. Therefore, 10 microM serotonin was added to the assays to prevent (-)ICYP binding to serotonin receptors. Under these conditions, (-)ICYP binding to the cortical membrane preparation was reversible and saturable, and the association reaction was very slow. The dissociation reaction was also very slow, and revealed two affinity states corresponding to a high and a low affinity state. Scatchard analysis showed a single class of binding sites with an equilibrium dissociation constant (KD) of 20.7 pM, and a maximal density of binding sites (Bmax) of 95.1 fmol/mg membrane protein. Displacement binding analyses revealed a potency series of (-) isoproterenol greater than (-) epinephrine equal to (-) norepinephrine, suggesting a predominance of the beta 1 adrenoceptor subtype. Detailed competition ligand binding studies with the selective beta 1 adrenoceptor antagonist ICI-89406 and the selective beta 2 adrenoceptor antagonist ICI-118551, showed that about 70% of the beta adrenoceptor population in the rat cortex is of the beta 1 subtype with the remainder being of the beta 2 subtype. We conclude that since (-)ICYP binds to both beta adrenoceptors and serotonin receptors, it is important to prevent the binding of (-)ICYP to serotonin receptors by adding a suppressing ligand like excess cold serotonin when assaying beta adrenoceptors. We have presented the first such characterization of rat cerebral cortical beta adrenoceptors with (-)ICYP in this study

  10. In vivo cellular uptake of glutamate is impaired in the rat hippocampus during and after transient cerebral ischemia

    DEFF Research Database (Denmark)

    Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

    2001-01-01

    Using microdialysis in CA1 of the rat hippocampus, we studied the effect of transient cerebral ischemia on in vivo uptake and on extracellular levels of glutamate during, and at different time points after ischemia. (3)H-D-aspartate (test substance), and (14)C-mannitol (reference substance), were...

  11. [Effect of electric acupuncture on the expression of NgR in the cerebral cortex, the medulla oblongata, and the spinal cord of hypertensive rats after cerebral infarction].

    Science.gov (United States)

    Tan, Feng; Chen, Jie; Liang, Yan-Gui; Li, Yan-Ping; Wang, Xue-Wen; Meng, Di; Cheng, Nan-Fang

    2014-03-01

    To observe the effect of electric acupuncture (EA) on the Nogo receptors (NgR) protein expression in the cerebral cortex, the medulla oblongata, and the spinal cord of cerebral ischemia-reperfusion (I/R) stroke-prone renovascular hypertensive rats (RHRSP) with middle cerebral artery occlusion (MCAO) at different time points, and to investigate its possible mechanisms for remote-organ injury of acute cerebral infarction (ACI). The RHRSP model was duplicated in male SPF grade SD rats. Then the MCAO model was prepared by a thread stringing method. Rats were divided into the hypertension group,the sham-operation group, the MCAO group, the EA group, and the sham-acupoint group by random number table method, 60 in each group. Rats in the MCAO group only received MCAO reperfusion treatment. Those in the sham-operation group only received surgical trauma. Baihui (DU20) and Dazhui (DU14) were needled in the EA group, once daily for a total of 28 days.The needles were acupunctured at the skin one cun distant from Baihui (DU20) and Dazhui (DU14) and then the same EA treatment was performed in the sham-acupoint group. At day 1, 7, 14, 28 after treatment, six rats were executed from each group, and their right cortex and medulla oblongata, and the left spinal cord were isolated. The infarct volume was detected by Nissl's staining method. The NgR expression was detect by Western blot. (1) In the cortex area: compared with the hypertension group,the NgR expression increased in the MCAO group at day 1,7,14,and 28 after MCAO (P 0.05). At day 7, 14,and 28 after MCAO, the NgR expression decreased in the EA group (P 0.05). (2) In the medulla oblongata area: compared with the hypertension group, the NgR expression was equivalent in the sham-operation group. the MCAO group,the EA group, and the sham-acupoint group at 1 day after MCAO (P > 0.05). At day 7.14, and 28 after MCAO, the NgR expression increased in the MCAO group (P 0.05). (3) In the spinal cord area: compared with the

  12. Alterations of local cerebral glucose utilization in lean and obese fa/fa rats after acute adrenalectomy.

    Science.gov (United States)

    Doyle, P; Rohner-Jeanrenaud, F; Jeanrenaud, B

    1994-08-29

    An animal model often used to investigate the aetiology of obesity is the genetically obese fa/fa rat. It has many abnormalities, including hyperphagia, hyper-insulinemia, insulin resistance, low cerebral glucose utilization and an overactive hypothalamo-pituitary adrenal (HPA) axis with resulting hypercorticism. Due to the latter consideration, the aim of this work was to study the impact of acute adrenalectomy (ADX) on the local cerebral glucose utilization (LCGU) of lean and obese fa/fa rats. ADX resulted in discrete increases in LCGU of regions common to both lean and obese rats. These common regions were found to belong to be related to the limbic system. Within this system, the LCGU of the brain of obese rats was either normalized to lean sham operated values or increased by ADX to a similar degree in both groups on a percentage basis. It was concluded that the LCGU of both lean and obese animals appears to be negatively regulated, albeit to different extents, by glucocorticoids. Such negative regulation is particularly salient within the limbic system of the lean rat and even more so in the fa/fa rat. It is suggested that the long-term hypercorticism of obese fa/fa rats due to abnormal regulation of the HPA axis may result in a decreased LCGU in limbic and related regions of the brain of fa/fa rats and contribute to the expression of the obese phenotype.

  13. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    Science.gov (United States)

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  14. Short-term sleep deprivation stimulates hippocampal neurogenesis in rats following global cerebral ischemia/reperfusion.

    Directory of Open Access Journals (Sweden)

    Oumei Cheng

    Full Text Available Sleep deprivation (SD plays a complex role in central nervous system (CNS diseases. Recent studies indicate that short-term SD can affect the extent of ischemic damage. The aim of this study was to investigate whether short-term SD could stimulate hippocampal neurogenesis in a rat model of global cerebral ischemia/reperfusion (GCIR.One hundred Sprague-Dawley rats were randomly divided into Sham, GCIR and short-term SD groups based on different durations of SD; the short-term SD group was randomly divided into three subgroups: the GCIR+6hSD*3d-treated, GCIR+12hSD-treated and GCIR+12hSD*3d-treated groups. The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and hemorrhagic hypotension. The rats were sleep-deprived starting at 48 h following GCIR. A Morris water maze test was used to assess learning and memory ability; cell proliferation and differentiation were analyzed via 5-bromodeoxyuridine (BrdU and neuron-specific enolase (NSE, respectively, at 14 and 28 d; the expression of hippocampal BDNF was measured after 7 d.The different durations of short-term SD designed in our experiment exhibited improvement in cognitive function as well as increased hippocampal BDNF expression. Additionally, the short-term SD groups also showed an increased number of BrdU- and BrdU/NSE-positive cells compared with the GCIR group. Of the three short-term SD groups, the GCIR+12hSD*3d-treated group experienced the most substantial beneficial effects.Short-term SD, especially the GCIR+12hSD*3d-treated method, stimulates neurogenesis in the hippocampal dentate gyrus (DG of rats that undergo GCIR, and BDNF may be an underlying mechanism in this process.

  15. Curcumin inhibits endoplasmic reticulum stress induced by cerebral ischemia-reperfusion injury in rats

    Science.gov (United States)

    Zhu, Haiying; Fan, Yanxia; Sun, Hongyu; Chen, Liyan; Man, Xiao

    2017-01-01

    The aim of the present study was to observe the dynamic changes of the growth arrest and DNA damage-inducible 153 (GADD153) gene and caspase-12 in the brain tissue of rats with cerebral ischemia-reperfusion injury (CIRI) and the impact of curcumin pretreatment. A total of 60 rats were randomly divided into the normal group (N), the sham operation group (S), the dimethyl sulfoxide control group (D) and the curcumin treatment group (C). For group D and C, 12 (T1), 24 (T2) and 72 h (T3) of reperfusion were performed after 2 h ischemia. The expression levels of GADD153 and caspase-12 in the brain tissue were detected and compared among the groups by immunohistochemistry, immunofluorescence double staining and western blotting. The expression levels of GADD153 and caspase-12 were increased at T1compared with groups N and S, and the expression of caspase-12 peaked at T2 in group D, while GADD153 was increased until T3 in group D. Compared with group D, the expression levels of GADD153 and caspase-12 in group C at T2 and T3 were significantly decreased (P<0.05). Endoplasmic reticulum stress is involved in the pathological process of CIRI. Curcumin may decrease the expression levels of the above two factors, thus exhibiting protective effects against CIRI in rats. PMID:29067098

  16. Effect of heroin-conditioned auditory stimuli on cerebral functional activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Trusk, T.C.; Stein, E.A.

    1988-08-01

    Cerebral functional activity was measured as changes in distribution of the free fatty acid (1-14C)octanoate in autoradiograms obtained from rats during brief presentation of a tone previously paired to infusions of heroin or saline. Rats were trained in groups of three consisting of one heroin self-administering animal and two animals receiving yoked infusions of heroin or saline. Behavioral experiments in separate groups of rats demonstrated that these training parameters imparts secondary reinforcing properties to the tone for animals self-administering heroin while the tone remains behaviorally neutral in yoked-infusion animals. The optical densities of thirty-seven brain regions were normalized to a relative index for comparisons between groups. Previous pairing of the tone to heroin infusions irrespective of behavior (yoked-heroin vs. yoked-saline groups) produced functional activity changes in fifteen brain areas. In addition, nineteen regional differences in octanoate labeling density were evident when comparison was made between animals previously trained to self-administer heroin to those receiving yoked-heroin infusions, while twelve differences were noted when comparisons were made between the yoked vehicle and self administration group. These functional activity changes are presumed related to the secondary reinforcing capacity of the tone acquired by association with heroin, and may identify neural substrates involved in auditory signalled conditioning of positive reinforcement to opiates.

  17. Effect of heroin-conditioned auditory stimuli on cerebral functional activity in rats

    International Nuclear Information System (INIS)

    Trusk, T.C.; Stein, E.A.

    1988-01-01

    Cerebral functional activity was measured as changes in distribution of the free fatty acid [1-14C]octanoate in autoradiograms obtained from rats during brief presentation of a tone previously paired to infusions of heroin or saline. Rats were trained in groups of three consisting of one heroin self-administering animal and two animals receiving yoked infusions of heroin or saline. Behavioral experiments in separate groups of rats demonstrated that these training parameters imparts secondary reinforcing properties to the tone for animals self-administering heroin while the tone remains behaviorally neutral in yoked-infusion animals. The optical densities of thirty-seven brain regions were normalized to a relative index for comparisons between groups. Previous pairing of the tone to heroin infusions irrespective of behavior (yoked-heroin vs. yoked-saline groups) produced functional activity changes in fifteen brain areas. In addition, nineteen regional differences in octanoate labeling density were evident when comparison was made between animals previously trained to self-administer heroin to those receiving yoked-heroin infusions, while twelve differences were noted when comparisons were made between the yoked vehicle and self administration group. These functional activity changes are presumed related to the secondary reinforcing capacity of the tone acquired by association with heroin, and may identify neural substrates involved in auditory signalled conditioning of positive reinforcement to opiates

  18. Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

    OpenAIRE

    Valenti, Vitor E.; Abreu, Luiz Carlos de; Fonseca, Fernando L. A.; Adami, Fernando; Sato, Monica A.; Vanderlei, Luiz Carlos M.; Ferreira, Lucas Lima; Rodrigues, Luciano M.; Ferreira, Celso

    2013-01-01

    OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4...

  19. Hyperthyroidism modifies ecto-nucleotidase activities in synaptosomes from hippocampus and cerebral cortex of rats in different phases of development.

    Science.gov (United States)

    Bruno, Alessandra Nejar; Da Silva, Rosane Souza; Bonan, Carla Denise; Battastini, Ana Maria Oliveira; Barreto-chaves, Maria Luiza M; Sarkis, João José Freitas

    2003-11-01

    Here we investigate the possible effects of the hyperthyroidism on the hydrolysis of the ATP to adenosine in the synaptosomes of hippocampus, cerebral cortex and blood serum of rats in different developmental phases. Manifestations of hyperthyroidism include anxiety, nervousness, tachycardia, physical hyperactivity and weight loss amongst others. The thyroid hormones modulate a number of physiological functions in central nervous system, including development, function, expression of adenosine A(1) receptors and transport of neuromodulator adenosine. Thus, hyperthyroidism was induced in male Wistar rats (5-, 60-, 150- and 330-day old) by daily injections of L-thyroxine (T4) for 14 days. Nucleotide hydrolysis was decreased by about 14-52% in both hippocampus and cerebral cortex in 5 to 60-day-old rats. These changes were also observed in rat blood serum. In addition, in 11-month-old rats, inhibition of ADP and AMP hydrolysis persisted in the hippocampus, whereas, in cerebral cortex, an increase in AMP hydrolysis was detected. Thus, hyperthyroidism affects the extracellular nucleotides balance and adenosine production, interfering in neurotransmitter release, development and others physiological processes in different systems.

  20. Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

    Directory of Open Access Journals (Sweden)

    Shen J

    2017-09-01

    Full Text Available Junyi Shen, Zhiming Zhao, Wei Shang, Chunli Liu, Beibei Zhang, Lingjie Zhao, Hui Cai Department of Integrated Traditional and Western Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China Abstract: Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1 has a wide variety of therapeutic values for central nervous system (CNS diseases for the neuron protective effects. However, the blood–brain barrier (BBB restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H, Rg1, and OX26 antibody, targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction. Keywords: poly-γ-glutamic acid, ginsenoside Rg1, OX26, blood–brain barrier

  1. Postnatal changes in local cerebral blood flow measured by the quantitative autoradiographic [14C]iodoantipyrine technique in freely moving rats

    International Nuclear Information System (INIS)

    Nehlig, A.; Pereira de Vasconcelos, A.; Boyet, S.

    1989-01-01

    The postnatal changes in local cerebral blood flow in freely moving rats were measured by means of the quantitative autoradiographic [ 14 C]iodoantipyrine method. The animals were studied at 10, 14, 17, 21 and 35 days and at the adult stage. At 10 days after birth, rates of blood flow were very low and quite homogeneous in most cerebral structures except in a few posterior areas. From these relatively uniform levels, values of local cerebral blood flow rose notably to reach a peak at 17 days in all brain regions studied. Rates of blood flow decreased between 17 and 21 days after birth and then increased from weaning time to reach the known characteristic distribution of the adult rat. The postnatal evolution of local cerebral blood in the rat is in good agreement with previous studies in other species such as dog and humans that also show higher rates of cerebral blood flow and glucose utilization at immature stages. However, in the rat, local cerebral blood flow and local cerebral glucose utilization are not coupled over the whole postnatal period studied, since blood flow rates reach peak values at 17 days whereas glucose utilization remains still quite low at that stage. The high rate of cerebral blood flow in the 17-day-old rat may reflect the energetic and biosynthetic needs of the actively developing brain that are completed by the summation of glucose and ketone body utilization

  2. Carbon balance studies of glucose metabolism in rat cerebral cortical synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, U; Brand, K

    1982-07-01

    Synaptosomes were isolated from rat cerebral cortex and incubated with (U-/sup 14/C)-, (1-/sup 14/C)- or (6-/sup 14/C)glucose. Glucose utilization and the metabolic partitioning of glucose carbon in products were determined by isotopic methods. From the data obtained a carbon balance was constructed, showing lactate to be the main product of glucose metabolism, followed by CO/sup 2/, amino acids and pyruvate. Measuring the release of /sup 14/CO/sup 2/ from glucose labelled in three different positions allowed the construction of a flow diagram of glucose carbon atoms in synaptosomes, which provides information about the contribution of the various pathways of glucose metabolism. Some 2% of glucose utilized was calculated to be degraded via the pentose phosphate pathway. Addition of chlorpromazine, imipramine or haloperidol at concentrations of 10(-5) M reduced glucose utilisation by 30% without changing the distribution pattern of radioactivity in the various products.

  3. Effects of activated ACM on expression of signal transducers in cerebral cortical neurons of rats.

    Science.gov (United States)

    Wang, Xiaojing; Li, Zhengli; Zhu, Changgeng; Li, Zhongyu

    2007-06-01

    To explore the roles of astrocytes in the epileptogenesis, astrocytes and neurons were isolated, purified and cultured in vitro from cerebral cortex of rats. The astrocytes were activated by ciliary neurotrophic factor (CNTF) and astrocytic conditioned medium (ACM) was collected to treat neurons for 4, 8 and 12 h. By using Western blot, the expression of calmodulin dependent protein kinase II (CaMK II), inducible nitric oxide synthase (iNOS) and adenylate cyclase (AC) was detected in neurons. The results showed that the expression of CaMK II, iNOS and AC was increased significantly in the neurons treated with ACM from 4 h to 12 h (PACM and such signal pathways as NOS-NO-cGMP, Ca2+/CaM-CaMK II and AC-cAMP-PKA might take part in the signal transduction of epileptogenesis.

  4. Neuroprotective capabilities of TSA against cerebral ischemia/reperfusion injury via PI3K/Akt signaling pathway in rats.

    Science.gov (United States)

    Ma, Xiao-Hui; Gao, Qiang; Jia, Zhen; Zhang, Ze-Wei

    2015-02-01

    Hundreds of previous studies demonstrated the cytoprotective effect of trichostatin-A (TSA), a kind of histone deacetylases inhibitors (HDACIs), against cerebral ischemia/reperfusion insult. Meanwhile, phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is a well-known, important signaling pathway that mediates neuroprotection. However, it should be remains unclear whether the neuroprotective capabilities of TSA against cerebral ischemia/reperfusion is mediated by activation of the PI3K/Akt signaling pathway. Five groups rats (n = 12 each), with middle cerebral artery occlusion (MCAO) except sham group, were used to investigate the neuroprotective effect of certain concentration (0.05 mg/kg) of TSA, and whether the neuroprotective effect of TSA is associated with activation of the PI3K/Akt signaling pathway through using of wortmannin (0.25 mg/kg). TSA significantly increased the expression of p-Akt protein, reduced infarct volume, and attenuated neurological deficit in rats with transient MCAO, wortmannin weakened such effect of TSA dramatically. TSA could significantly decrease the neurological deficit scores and reduce the cerebral infarct volume during cerebral ischemia/reperfusion injury, which was achieved partly by activation of the PI3K/Akt signaling pathway via upgrading of p-Akt protein.

  5. Pericyte protection by edaravone after tissue plasminogen activator treatment in rat cerebral ischemia

    Science.gov (United States)

    Deguchi, Kentaro; Liu, Ning; Liu, Wentao; Omote, Yoshio; Kono, Syoichiro; Yunoki, Taijun; Deguchi, Shoko; Yamashita, Toru; Ikeda, Yoshio; Abe, Koji

    2014-01-01

    Pericytes play a pivotal role in contraction, mediating inflammation and regulation of blood flow in the brain. In this study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. Immunohistochemistry and Western blot analyses showed that the overlap between platelet-derived growth factor receptor β-positive pericytes and N-acetylglucosamine oligomers (NAGO)-positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). The number of pericytes and the overlap with NAGO decreased with tPA but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treatment damaged pericytes, resulting in the detachment from astrocytes and a decrease in glial cell line-derived neurotrophic factor secretion. However, treatment with edaravone greatly improved tPA-induced damage to pericytes. The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can greatly ameliorate such damage after acute cerebral ischemia in rats. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID:24938625

  6. MR imaging of cerebral lesions accompanying stroke in stroke-prone spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Takahashi, Masaya; Fritz-Zieroth, B.; Yamaguchi, Motonori; Ogawa, Hiroshi; Tanaka, Tomoyo; Sasagawa, Sukenari; Chikugo, Taka-aki; Ohta, Yoshio; Okamoto, Kozo.

    1992-01-01

    Cerebral lesions accompanying stroke in male stroke-prone spontaneously hypertensive rats (SHRSP, n=10) were examined by both magnetic resonance imaging (MRI) and histological evaluation. T2-weighted MR images (T2-WI), taken 1-2 days after animals showed behavioral hyperactivity, indicated hyperintense regions in the occipital cortex, caudate putamen and/or thalamus. The areas of hyperintensity on T2-WI corresponded to neurodegenerative regions including edema, gliosis, and softening of the tissue. T1-weighted images (T1-WI) did not show any hyperintense regions. However T1-weighted images enhanced by the contrast media Gd-DTPA (Gd-T1-WI) showed hyperintense spots within some of the hyperintense areas on T2-WI, which exhibited neurodegenerative regions such as thrombus, angionecrosis and hemorrhage in addition to the edematous formation. The hyperintense areas on Gd-T1-WI were smaller than those on T2-WI. In some animals, hypointense spots on T2-, T1- and Gd-T1-WI were found within the hyperintense areas, which corresponded to clots. Extensive histological examination did not reveal any additional cerebral degeneration which had not been detected on the MR images. These findings indicate that MRI is useful for detecting and differentiating various types of cerebrovascular diseases in this model. (author)

  7. Piracetam improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.

    Science.gov (United States)

    He, Zhi; Liao, Yun; Zheng, Min; Zeng, Fan-Dian; Guo, Lian-Jun

    2008-06-01

    Piracetam is the derivate of gamma-aminobutyric acid, which improves the cognition,memory,consciousness, and is widely applied in the clinical treatment of brain dysfunction. In the present experiments, we study the effects of piracetam on chronic cerebral hypoperfused rats and observe its influence on amino acids, synaptic plasticity in the Perforant path-CA3 pathway and apoptosis in vivo. Cerebral hypoperfusion for 30 days by occlusion of bilateral common carotid arteries induced marked amnesic effects along with neuron damage, including: (1) spatial learning and memory deficits shown by longer escape latency and shorter time spent in the target quadrant; (2) significant neuronal loss and nuclei condensation in the cortex and hippocampus especially in CA1 region; (3) lower induction rate of long term potentiation, overexpression of BAX and P53 protein, and lower content of excitatory and inhibitory amino acids in hippocampus. Oral administration of piracetam (600 mg/kg, once per day for 30 days) markedly improved the memory impairment, increased the amino acid content in hippocampus, and attenuated neuronal damage. The ability of piracetam to attenuate memory deficits and neuronal damage after hypoperfusion may be beneficial in cerebrovascular type dementia.

  8. MR imaging of cerebral lesions accompanying stroke in stroke-prone spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masaya; Fritz-Zieroth, B.; Yamaguchi, Motonori (Nihon Schering K.K., Osaka (Japan)); Ogawa, Hiroshi; Tanaka, Tomoyo; Sasagawa, Sukenari; Chikugo, Taka-aki; Ohta, Yoshio; Okamoto, Kozo

    1992-07-01

    Cerebral lesions accompanying stroke in male stroke-prone spontaneously hypertensive rats (SHRSP, n=10) were examined by both magnetic resonance imaging (MRI) and histological evaluation. T2-weighted MR images (T2-WI), taken 1-2 days after animals showed behavioral hyperactivity, indicated hyperintense regions in the occipital cortex, caudate putamen and/or thalamus. The areas of hyperintensity on T2-WI corresponded to neurodegenerative regions including edema, gliosis, and softening of the tissue. T1-weighted images (T1-WI) did not show any hyperintense regions. However T1-weighted images enhanced by the contrast media Gd-DTPA (Gd-T1-WI) showed hyperintense spots within some of the hyperintense areas on T2-WI, which exhibited neurodegenerative regions such as thrombus, angionecrosis and hemorrhage in addition to the edematous formation. The hyperintense areas on Gd-T1-WI were smaller than those on T2-WI. In some animals, hypointense spots on T2-, T1- and Gd-T1-WI were found within the hyperintense areas, which corresponded to clots. Extensive histological examination did not reveal any additional cerebral degeneration which had not been detected on the MR images. These findings indicate that MRI is useful for detecting and differentiating various types of cerebrovascular diseases in this model. (author).

  9. Culturated rat cerebral cortex explants and their application in the study of SPECT scan radiopharaceuticals

    International Nuclear Information System (INIS)

    Jong, B.M. de.

    1989-01-01

    In this thesis mechanics that result in the distinct localization of radiopharmaceuticals within the brain have been investigated. In order to 'get more insight' in uptake and binding of radiopharmaceuticals bu brain tissue, use has been made of the tissue culture technique. Tissue culture privides the opportunity of doing experiments with brain tissue under stable conditions, in the absence of a blood-brain barrier, and without interference by cerebral blood flow. The present thesis is presented in two sections. The first part focusses on longterm culture of 'organotypic' cerebral neocortex tissue, obtained from neonatal rat brain and explanted into a chemically defined medium. Procedures were developed which enabled culturing of this tissue without the occurence of central necrosis and with the preservation of a characteristic histiotypic organization. Morphological characteristics of the cultures were described and measured at various ages in vitro. In the second part, the cultures were used to study mechanisms that might contribute to the tissue uptake of radiopharmaceuticals which are in clinical use for SPECT brain imaging. (author). 369 refs.; 50 figs.; 13 tabs

  10. Neuroprotective effects of andrographolide in a rat model of permanent cerebral ischaemia

    Science.gov (United States)

    Chan, Su Jing; Wong, WS Fred; Wong, Peter TH; Bian, Jin-Song

    2010-01-01

    BACKGROUND AND PURPOSE Andrographolide is a diterpenoid lactone isolated from a traditional medicinal herb, Andrographis paniculata. It possesses potent anti-inflammatory activity. The present study examined potential therapeutic effects of andrographolide on cerebral ischaemia using a rat model with permanent middle cerebral artery occlusion (pMCAO). EXPERIMENTAL APPROACH The MCA in rats was permanently occluded (by cautery), and 24 h later neurological effects were assessed with behavioural scores. Infarct volume and microglial activation were determined histologically. The p65 form of the transcription factor, nuclear factor-κB (NF-κB), was measured by Western blot, and cytokines by immunoassay of brain extracts. KEY RESULTS Andrographolide, given i.p. 1 h after pMCAO, reduced infarct volume with a maximum reduction of approximately 50% obtained at 0.1 mg·kg−1. Neurological deficits were also reduced by andrographolide, reflecting a correlation between infarct volume and neurological deficits. pMCAO was found to induce activation of microglia and elevate tumour necrosis factor (TNF)-α, interleukin (IL)-1β and prostaglandin (PG)E2 in the ischaemic brain areas. Andrographolide (0.1 mg·kg−1) significantly attenuated or abolished these effects. In addition, andrographolide suppressed the translocation of p65 from cytosol to nucleus, indicating reduced NF-κB activation. CONCLUSIONS AND IMPLICATIONS Andrographolide exhibited neuroprotective effects, with accompanying suppression of NF-κB and microglial activation, and reduction in the production of cytokines including TNF-α and IL-1β, and pro-inflammatory factors such as PGE2. Our findings suggest that andrographolide may have therapeutic value in the treatment of stroke. PMID:20880404

  11. Effect of donepezil hydrochloride (E2020) on extracellular acetylcholine concentration in the cerebral cortex of rats.

    Science.gov (United States)

    Kosasa, T; Kuriya, Y; Yamanishi, Y

    1999-10-01

    Donepezil hydrochloride (donepezil), a potent and selective acetylcholinesterase inhibitor, has been developed for the treatment of Alzheimer's disease. We studied the effect of oral administration of this drug on the extracellular acetylcholine (ACh) concentration in the cerebral cortex of rats using microdialysis. We also observed fasciculation, a peripheral cholinergic sign induced by activation of neuromuscular transmission, after oral administration of the drug as an index of peripheral cholinergic activation. Other cholinesterase inhibitors, tacrine, ENA-713 and TAK-147, were used as reference drugs. Donepezil significantly and dose-dependently increased the extracellular ACh concentration in the rat cerebral cortex within the dose range of 2.5-10 mg/kg. Tacrine, ENA-713 and TAK-147 also elevated the extracellular concentration of ACh. The minimum effective doses of donepezil, tacrine, ENA-713 and TAK-147 were (< or = 2.5, 10, 10 and < or = 10 mg/kg, respectively. Donepezil produced fasciculation at doses of 2.5 mg/kg and above, with a dose-dependent increase in incidence and intensity. The reference compounds also induced fasciculation in a dose-dependent manner. The threshold doses of tacrine, ENA-713 and TAK-147 for fasciculation were 5, 2.5 and 2.5 mg/kg, respectively. The values of the ratio of the minimum effective dose for the ACh-increasing action to that for the fasciculation-producing action were: donepezil, < or = 1; tacrine, 2; ENA-713, 4; TAK-147, < or = 4. These results indicate that orally administered donepezil has a potent and selective activity on the central cholinergic system.

  12. Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion

    Directory of Open Access Journals (Sweden)

    Ying Yang

    2017-01-01

    Full Text Available Hypoxia inducible factor 1α (HIF-1α, a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs, were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit.

  13. Effects of Edaravone, a Free Radical Scavenger, on Photochemically Induced Cerebral Infarction in a Rat Hemiplegic Model

    Directory of Open Access Journals (Sweden)

    Satoshi Ikeda

    2013-01-01

    Full Text Available Edaravone is a free radical scavenger that protects the adjacent cortex during cerebral infarction. We created a hemiparetic model of cerebral thrombosis from a photochemically induced infarction with the photosensitive dye, rose bengal, in rats. We examined the effects of edaravone on recovery in the model. A total of 36 adult Wistar rats were used. The right sensorimotor area was irradiated with green light with a wavelength of 533 nm (10 mm diameter, and the rose bengal was injected intravenously to create an infarction. The edaravone group was injected intraperitoneally with edaravone (3 mg/kg, and the control group was injected with saline. The recovery process of the hemiplegia was evaluated with the 7-step scale of Fenny. The infarcted areas were measured after fixation. The recovery of the paralysis in the edaravone-treated group was significantly earlier than that in the untreated group. Seven days later, both groups were mostly recovered and had scores of 7, and the infarction region was significantly smaller in the edaravone-treated group. Edaravone reduced the infarction area and promoted the functional recovery of hemiparesis from cerebral thrombosis in a rat model. These findings suggest that edaravone treatment would be effective in clinical patients recovering from cerebral infarction.

  14. Effects of edaravone, a free radical scavenger, on photochemically induced cerebral infarction in a rat hemiplegic model.

    Science.gov (United States)

    Ikeda, Satoshi; Harada, Katsuhiro; Ohwatashi, Akihiko; Kamikawa, Yurie

    2013-01-01

    Edaravone is a free radical scavenger that protects the adjacent cortex during cerebral infarction. We created a hemiparetic model of cerebral thrombosis from a photochemically induced infarction with the photosensitive dye, rose bengal, in rats. We examined the effects of edaravone on recovery in the model. A total of 36 adult Wistar rats were used. The right sensorimotor area was irradiated with green light with a wavelength of 533 nm (10 mm diameter), and the rose bengal was injected intravenously to create an infarction. The edaravone group was injected intraperitoneally with edaravone (3 mg/kg), and the control group was injected with saline. The recovery process of the hemiplegia was evaluated with the 7-step scale of Fenny. The infarcted areas were measured after fixation. The recovery of the paralysis in the edaravone-treated group was significantly earlier than that in the untreated group. Seven days later, both groups were mostly recovered and had scores of 7, and the infarction region was significantly smaller in the edaravone-treated group. Edaravone reduced the infarction area and promoted the functional recovery of hemiparesis from cerebral thrombosis in a rat model. These findings suggest that edaravone treatment would be effective in clinical patients recovering from cerebral infarction.

  15. Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

    Science.gov (United States)

    Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

    2014-01-01

    Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

  16. Zinc translocation accelerates infarction after mild transient focal ischemia.

    Science.gov (United States)

    Lee, J-M; Zipfel, G J; Park, K H; He, Y Y; Hsu, C Y; Choi, D W

    2002-01-01

    Excess release of chelatable zinc (Zn(2+)) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn(2+), and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn(2+) chelator, EDTA saturated with equimolar Ca(2+) (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn(2+) translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn(2+) translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

  17. Near-infrared diffuse reflectance imaging of infarct core and peri-infarct depolarization in a rat middle cerebral artery occlusion model

    Science.gov (United States)

    Kawauchi, Satoko; Nishidate, Izumi; Nawashiro, Hiroshi; Sato, Shunichi

    2014-03-01

    To understand the pathophysiology of ischemic stroke, in vivo imaging of the brain tissue viability and related spreading depolarization is crucial. In the infarct core, impairment of energy metabolism causes anoxic depolarization (AD), which considerably increases energy consumption, accelerating irreversible neuronal damage. In the peri-infarct penumbra region, where tissue is still reversible despite limited blood flow, peri-infarct depolarization (PID) occurs, exacerbating energy deficit and hence expanding the infarct area. We previously showed that light-scattering signal, which is sensitive to cellular/subcellular structural integrity, was correlated with AD and brain tissue viability in a rat hypoxia-reoxygenation model. In the present study, we performed transcranial NIR diffuse reflectance imaging of the rat brain during middle cerebral artery (MCA) occlusion and examined whether the infarct core and PIDs can be detected. Immediately after occluding the left MCA, light scattering started to increase focally in the occlusion site and a bright region was generated near the occlusion site and spread over the left entire cortex, which was followed by a dark region, showing the occurrence of PID. The PID was generated repetitively and the number of times of occurrence in a rat ranged from four to ten within 1 hour after occlusion (n=4). The scattering increase in the occlusion site was irreversible and the area with increased scattering expanded with increasing the number of PIDs, indicating an expansion of the infarct core. These results suggest the usefulness of NIR diffuse reflectance signal to visualize spatiotemporal changes in the infarct area and PIDs.

  18. Focal myositis

    International Nuclear Information System (INIS)

    Kransdorf, M.J.; Temple, H.T.; Sweet, D.E.

    1998-01-01

    Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.)

  19. La atorvastatina protege las neuronas gabérgicas y dopaminérgicas del sistema nigroestriatal en un modelo experimental de isquemia cerebral focal transitoria en ratas

    OpenAIRE

    Sabogal, Angélica María; Arango, César Augusto; Cardona, Gloria Patricia; Céspedes, Ángel Enrique

    2014-01-01

    Introduction: Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown. Objective: To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain...

  20. Propentofylline treatment on open field behavior in rats with focal ethidium bromide-induced demyelination in the ventral surface of the brainstem.

    Science.gov (United States)

    Martins-Júnior, J L; Bernardi, M M; Bondan, E F

    2016-03-01

    Propentofylline (PPF) is a xanthine derivative with pharmacological effects that are distinct from those of classic methylxanthines. It depresses the activation of microglial cells and astrocytes, which is associated with neuronal damage during neural inflammation and hypoxia. Our previous studies showed that PPF improved remyelination following gliotoxic lesions that were induced by ethidium bromide (EB). In the present study, the long-term effects of PPF on open field behavior in rats with EB-induced focal demyelination were examined. The effects of PPF were first evaluated in naive rats that were not subjected to EB lesions. Behavior in the beam walking test was also evaluated during chronic PPF treatment because impairments in motor coordination can interfere with behavior in the open field. The results showed that PPF treatment in unlesioned rats decreased general activity and caused motor impairment in the beam walking test. Gliotoxic EB injections increased general activity in rats that were treated with PPF compared with rats that received saline solution. Motor incoordination was also attenuated in PPF-treated rats. These results indicate that PPF reversed the effects of EB lesions on behavior in the open field and beam walking test. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The effects of low dose ionizing radiation on the development of rat cerebral cortex, (1)

    International Nuclear Information System (INIS)

    Matsushita, Koji

    1993-01-01

    We obtained the following results with regards to the effects of low dose ionizing radiation (5, 10, 15 and 20 cGy) on neuronal migration of developing rat cerebral cortex. Neuronal migration delay was found by autoradiography after intraperitoneal labeling with 3 H-thymidine to pregnant Wistar rats embryonic 16, and low dose radiation an hour or 48 hours after labeling. In 15-20 cGy, N-CAM (neural cell adhesion molecules) staining patterns changed with immunohistochemical method, whereas those of L1 and cytoskeleton neurofilament (160 KD), tauprotein, MAP2 (microtubule associated protein 2) did not. After 24-48 hours of radiation, N-CAM were not detected on the matrix cell layer. After 72-96 hours of radiation, N-CAM staining recovered to a normal pattern. In conclusion, low dose radiation of 15-20 cGy gave rise to neuronal migration delay and it was suggested that N-CAM may be related to neuronal migration as one of the mechanisms involved. (author)

  2. Developmental changes of mast cell populations in the cerebral meninges of the rat.

    Science.gov (United States)

    Michaloudi, Helen; Batzios, Christos; Chiotelli, Maria; Papadopoulos, Georgios C

    2007-10-01

    It is known that both the dura and the pia mater attract and support the differentiation of mast cells. The present study shows that unevenly distributed mast cells in the cerebral meninges of the rat can be found in perivascular sites and vessel ramification points, but can also be unrelated to the meningeal vasculature. It also documents changes in the number, localization and staining preferences of the mast cells in the two meninges of the developing and mature rat brain. Quantitative examination of all types of histochemically differentiated meningeal mast cells reveals no major (although some exist) differences between right and left side subpopulations, but strongly suggests a different origin and fate of the dural and the pial mast cells. The number of dural mast cells, already high from postnatal day 0, although declining from postnatal day 21 onwards, remains conspicuous up to postnatal day 180. In contrast, pial mast cells are comparatively very few in the first day of the postnatal life, and despite a transient significant increase in the following two weeks, they reach almost zero levels from postnatal day 21.

  3. Effects of Scrambling trumpet Creeper flavone on transient cerebral ischemia model (TIA) in rats.

    Science.gov (United States)

    Miao, Mingsan; Zhang, Xu; Zhang, Fan; Wang, Can; Fang, Xiaoyan; Bai, Ming; Xu, Cuishan; Teng, Leshang

    2018-03-01

    To investigate the effects of Scrambling Trumpet Creeper flavone on neurological function score, brain tissue lesion and related biochemical indexes in rat TIA model. Methods: TIA model was induced by tail vein injection of t-butanol (t-BHP). The rats in each administration group were given large, medium and low dose of Scrambling Trumpet Creeper flavone 0.1% CMC suspension, nimodipine and Yangxueqingnao particles group 0.1% CMC suspension, model group and blank group fed the same volume 0.1% CMC. Once a day, continuous administration of 7d. On the 3rd and 6th day after administration, t-BHP was injected into the tail vein, and then placed in a sealed 1 L jar. After 10 min of hypoxia, the neurological function score (NDS) was performed. After the first 2 days of TIA administration, the hem rheology was measured immediately after 1 h of administration, and blood rheology was measured immediately after the administration of blood, blood clotting, hematocrit, hematocrit and whole blood viscosity. After HE is staining to observe the pathological changes of hippocampus and cortex in the left-brain tissue. (LDH) and adenosine triphosphate (ATP) were measured. The right brain tissue of the cerebral cortex was observed. The expression of lactate (LD), lactate dehydrogenase (LDH) Fibroblast growth factor (FGF) and insulin growth factor (IGF) were detected by immunohistochemistry. Compared with the blank group, the coagulation time of the model rats was significantly shortened. The red blood cell deformation index was significantly decreased. Erythrocyte sedimentation rate, hematocrit, plasma viscosity, whole blood viscosity, erythrocyte rigidity index and blood sedimentation equation K value were significantly increased; LD content increased significantly, and LDH, ATP enzyme activity decreased significantly. The positive expression of FGF and IGF in the cortical area had a trend of increasing. The Scrambling Trumpet Creeper flavone significantly improved the

  4. Effects of Scrambling trumpet Creeper flavone on transient cerebral ischemia model (TIA in rats

    Directory of Open Access Journals (Sweden)

    Mingsan Miao

    2018-03-01

    Full Text Available To investigate the effects of Scrambling Trumpet Creeper flavone on neurological function score, brain tissue lesion and related biochemical indexes in rat TIA model. Methods: TIA model was induced by tail vein injection of t-butanol (t-BHP. The rats in each administration group were given large, medium and low dose of Scrambling Trumpet Creeper flavone 0.1% CMC suspension, nimodipine and Yangxueqingnao particles group 0.1% CMC suspension, model group and blank group fed the same volume 0.1% CMC. Once a day, continuous administration of 7d. On the 3rd and 6th day after administration, t-BHP was injected into the tail vein, and then placed in a sealed 1 L jar. After 10 min of hypoxia, the neurological function score (NDS was performed. After the first 2 days of TIA administration, the hem rheology was measured immediately after 1 h of administration, and blood rheology was measured immediately after the administration of blood, blood clotting, hematocrit, hematocrit and whole blood viscosity. After HE is staining to observe the pathological changes of hippocampus and cortex in the left-brain tissue. (LDH and adenosine triphosphate (ATP were measured. The right brain tissue of the cerebral cortex was observed. The expression of lactate (LD, lactate dehydrogenase (LDH Fibroblast growth factor (FGF and insulin growth factor (IGF were detected by immunohistochemistry. Results: Compared with the blank group, the coagulation time of the model rats was significantly shortened. The red blood cell deformation index was significantly decreased. Erythrocyte sedimentation rate, hematocrit, plasma viscosity, whole blood viscosity, erythrocyte rigidity index and blood sedimentation equation K value were significantly increased; LD content increased significantly, and LDH, ATP enzyme activity decreased significantly. The positive expression of FGF and IGF in the cortical area had a trend of increasing. Conclusion: The Scrambling Trumpet Creeper flavone

  5. Focal myositis

    International Nuclear Information System (INIS)

    Galloway, H.R.; Dahlstrom, J.E.; Bennett, G.M.

    2001-01-01

    Focal myositis is a rare, benign focal inflammation of muscle. The lesion often presents as a mass that may be mistaken for a soft tissue sarcoma. This report describes the MRI and histopathological features of a case and illustrates how the diagnosis may be suspected on the basis of the MR findings. Copyright (2001) Blackwell Science Pty Ltd

  6. Subarachnoid hemorrhage-induced upregulation of the 5-HT1B receptor in cerebral arteries in rats

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Hoel, Natalie Løvland; Xu, Cang-Bao

    2003-01-01

    experimental SAH. METHODS: Experimental SAH was induced in rats by using an autologous prechiasmatic injection of arterial blood. Two days later, the middle cerebral artery (MCA), posterior communicating artery (PCoA), and basilar artery (BA) were harvested and examined functionally with the aid of a sensitive...... RNA coding for the 5-HT1B receptor as determined by quantitative real-time PCR. In the PCoA no upregulation of the 5-HT1B receptor was observed. CONCLUSIONS: Changes in the receptor phenotype in favor of contractile receptors may well represent the end stage in a sequence of events leading from SAH...... to the actual development of cerebral vasospasm. Insight into the mechanism of upregulation may provide new targets for developing specific treatment against cerebral vasospasm....

  7. Exercise enhanced functional recovery and expression of GDNF after photochemically induced cerebral infarction in the rat.

    Science.gov (United States)

    Ohwatashi, Akihiko; Ikeda, Satoshi; Harada, Katsuhiro; Kamikawa, Yurie; Yoshida, Akira

    2013-01-01

    Exercise has been considered to affect the functional recovery from central nervous damage. Neurotrophic factors have various effects on brain damage. However, the effects of exercise for expression of GDNF on functional recovery with brain damage are not well known. We investigated the difference in functional recovery between non-exercise and beam-walking exercise groups, and the expression of GDNF in both groups after photochemical infarction. Adult male Wistar rats (N = 64) were used. Animals were divided into two groups: non-exercise (N = 35), and beam-walking exercise (N = 29). All rats underwent surgical photochemical infarction. The rats of the beam-walking group were trained every day to walk on a narrow beam after a one-day recovery period and those of the non-exercise group were left to follow a natural course. Animals were evaluated for hind limb function every day using a beam-walking task with an elevated narrow beam. The number of GDNF-like immunoreactive cells in the temporal cortex surrounding the lesion was counted 1, 3, 5, and 7 days after the infarction. Functional recovery of the beam-walking exercise group was significantly earlier than that of the non-exercise group. At 3 days after infarction, the number of GDNF-positive cells in the temporal cortex surrounding the infarction was significantly increased in the beam-walking exercise group compared with that in the non-exercise group. In the exercise group, motor function was remarkably recovered with the increased expression of GDNF-like immunoreactive cells. Our results suggested that a rehabilitative approach increased the expression of GDNF and facilitated functional recovery from cerebral infarction.

  8. Extracellular levels of lactate, but not oxygen, reflect sleep homeostasis in the rat cerebral cortex.

    Science.gov (United States)

    Dash, Michael B; Tononi, Giulio; Cirelli, Chiara

    2012-07-01

    It is well established that brain metabolism is higher during wake and rapid eye movement (REM) sleep than in nonrapid eye movement (NREM) sleep. Most of the brain's energy is used to maintain neuronal firing and glutamatergic transmission. Recent evidence shows that cortical firing rates, extracellular glutamate levels, and markers of excitatory synaptic strength increase with time spent awake and decline throughout NREM sleep. These data imply that the metabolic cost of each behavioral state is not fixed but may reflect sleep-wake history, a possibility that is investigated in the current report. Chronic (4d) electroencephalographic (EEG) recordings in the rat cerebral cortex were coupled with fixed-potential amperometry to monitor the extracellular concentration of oxygen ([oxy]) and lactate ([lac]) on a second-by-second basis across the spontaneous sleep-wake cycle and in response to sleep deprivation. Basic sleep research laboratory. Wistar Kyoto (WKY) adult male rats. N/A. Within 30-60 sec [lac] and [oxy] progressively increased during wake and REM sleep and declined during NREM sleep (n = 10 rats/metabolite), but with several differences. [Oxy], but not [lac], increased more during wake with high motor activity and/or elevated EEG high-frequency power. Meanwhile, only the NREM decline of [lac] reflected sleep pressure as measured by slow-wave activity, mirroring previous results for cortical glutamate. The observed state-dependent changes in cortical [lac] and [oxy] are consistent with higher brain metabolism during waking and REM sleep in comparison with NREM sleep. Moreover, these data suggest that glycolytic activity, most likely through its link with glutamatergic transmission, reflects sleep homeostasis.

  9. Malformation of the cerebral cortex of rats caused by embryonal exposure to x-ray

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, M [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    1978-03-01

    200 R x-ray was irradiated to rat embryos, 17 days of age, and changes of the brain were observed histologically from one hour after the irradiation until they grew up. At start, there was not a great damage in the formation of bundles of major and minor hemisphere commissure passing through the terminal plate, although many cells died or fell off in the new brain mantle. After that, callosal fibers did not reach the midline because of the tissue destruction around the midline, and growth of the stem of the corpus callosum was pressed down. Defect of the stem of the corpus callosum was recognized in adult rats. Surviving mother cells gathered irregularly on the wall of the ventricle at the time of the repair of destructed tissues, and they remained as they stood around the midline of the brain mantle without rearrangement. In adult rats, there was abnormal formation of the cerebral cortex within medullary substances. Marked hypoplasia was recognized in the II-IV layer of the new cortex, bundle branches of dendritic processes of pyramidal cells in the V layer were small in number, and the directions of dendritic processes were abnormal. Pyramidal cell layer of the hippocampus fell into disorder and the directions of dendritic processes were irregular. It was demonstrated by the measurement of cubic volume of each part of the brain using reconstruction method that not only marked hypoplasia of the new cortex and the hippocampus but also hypoplasia of the old cortex, the basal ganglion, and the thalamus in which it was thought to be little disorder in the past were clear.

  10. Malformation of the cerebral cortex of rats caused by embryonal exposure to x-ray

    International Nuclear Information System (INIS)

    Inoue, Minoru

    1978-01-01

    200 R x-ray was irradiated to rat embryos, 17 days of age, and changes of the brain were observed histologically from one hour after the irradiation until they grew up. At start, there was not a great damage in the formation of bundles of major and minor hemisphere commissure passing through the terminal plate, although many cells died or fell off in the new brain mantle. After that, callosal fibers did not reach the midline because of the tissue destruction around the midline, and growth of the stem of the corpus callosum was pressed down. Defect of the stem of the corpus callosum was recognized in adult rats. Surviving mother cells gathered irregularly on the wall of the ventricle at the time of the repair of destructed tissues, and they remained as they stood around the midline of the brain mantle without rearrangement. In adult rats, there was abnormal formation of the cerebral cortex within medullary substances. Marked hypoplasia was recognized in the II-IV layer of the new cortex, bundle branches of dendritic processes of pyramidal cells in the V layer were small in number, and the directions of dendritic processes were abnormal. Pyramidal cell layer of the hippocampus fell into disorder and the directions of dendritic processes were irregular. It was demonstrated by the measurement of cubic volume of each part of the brain using reconstruction method that not only marked hypoplasia of the new cortex and the hippocampus but also hypoplasia of the old cortex, the basal ganglion, and the thalamus in which it was thought to be little disorder in the past were clear. (Iwagami, H.)

  11. Microglia and macrophages are major sources of locally produced transforming growth factor-beta1 after transient middle cerebral artery occlusion in rats

    DEFF Research Database (Denmark)

    Lehrmann, E; Kiefer, R; Christensen, Thomas

    1998-01-01

    The potentially neurotrophic cytokine transforming growth factor-beta1 (TGF-beta1) is locally expressed following human stroke and experimental ischemic lesions, but the cellular source(s) and profile of induction have so far not been established in experimental focal cerebral ischemia. This stud...

  12. Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats

    Directory of Open Access Journals (Sweden)

    Takashi Kondoh

    2010-06-01

    Full Text Available Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid, arginine, and their combination on ischemic insults (cerebral edema and infarction and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed two days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg, arginine (0.6 g/kg, or their combined administration (0.6 g/kg each. Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg, were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction, especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.

  13. Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury

    International Nuclear Information System (INIS)

    Zhu, Haibo; He, Jie; Ye, Liang; Lin, Fei; Hou, Jian; Zhong, Yan; Jiang, Wanglin

    2015-01-01

    Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/β-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood–brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Ang1 and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr-3, VCAM-1, Ang1 and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/β-catenin and VEGF/CREB/Egr-3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Ang1 and Tie-2 expression. - Highlights: • Curculigoside A induces cell proliferation through Wnt5a/β-catenin pathway. • Curculigoside A induces angiogenesis via VEGF/CREB/Egr-3/VCAM-1 signaling axis. • Curculigoside A promotes blood vessel maturation via Ang1/Tie2 pathway.

  14. Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Haibo [School of Public Health and Management, Binzhou Medical University, Yantai (China); Institute of Toxicology, Binzhou Medical University, Yantai (China); He, Jie [State Key Laboratory of Long-acting Targeting Drug Delivery Technologies (Luye Pharma Group Ltd.), Yantai 264003 (China); Ye, Liang [School of Public Health and Management, Binzhou Medical University, Yantai (China); Institute of Toxicology, Binzhou Medical University, Yantai (China); Lin, Fei; Hou, Jian; Zhong, Yan [State Key Laboratory of Long-acting Targeting Drug Delivery Technologies (Luye Pharma Group Ltd.), Yantai 264003 (China); Jiang, Wanglin, E-mail: jwl518@163.com [School of Pharmaceutical Sciences, Institute of Materia Medica, Binzhou Medical University, Yantai (China)

    2015-11-01

    Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/β-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood–brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Ang1 and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr-3, VCAM-1, Ang1 and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/β-catenin and VEGF/CREB/Egr-3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Ang1 and Tie-2 expression. - Highlights: • Curculigoside A induces cell proliferation through Wnt5a/β-catenin pathway. • Curculigoside A induces angiogenesis via VEGF/CREB/Egr-3/VCAM-1 signaling axis. • Curculigoside A promotes blood vessel maturation via Ang1/Tie2 pathway.

  15. The effects of abnormalities of glucose homeostasis on the expression and binding of muscarinic receptors in cerebral cortex of rats.

    Science.gov (United States)

    Sherin, Antony; Peeyush, Kumar T; Naijil, George; Nandhu, Mohan Sobhana; Jayanarayanan, Sadanandan; Jes, Paul; Paulose, Cheramadathikudiyil Skaria

    2011-01-25

    Glucose homeostasis in humans is an important factor for the functioning of nervous system. Both hypo and hyperglycemia contributes to neuronal functional deficit. In the present study, effect of insulin induced hypoglycemia and streptozotocin induced diabetes on muscarinic receptor binding, cholinergic enzymes; AChE, ChAT expression and GLUT3 in the cerebral cortex of experimental rats were analysed. Total muscarinic, muscarinic M(1) receptor showed a significant decrease and muscarinic M(3) receptor subtype showed a significant increased binding in the cerebral cortex of hypoglycemic rats compared to diabetic and control. Real-Time PCR analysis of muscarinic M(1), M(3) receptor subtypes confirmed the receptor binding studies. Immunohistochemistry of muscarinic M(1), M(3) receptors using specific antibodies were also carried out. AChE and GLUT3 expression up regulated and ChAT expression down regulated in hypoglycemic rats compared to diabetic and control rats. Our results showed that hypo/hyperglycemia caused impaired glucose transport in neuronal cells as shown by altered expression of GLUT3. Increased AChE and decreased ChAT expression is suggested to alter cortical acetylcholine metabolism in experimental rats along with altered muscarinic receptor binding in hypo/hyperglycemic rats, impair cholinergic transmission, which subsequently lead to cholinergic dysfunction thereby causing learning and memory deficits. We observed a prominent cholinergic functional disturbance in hypoglycemic condition than in hyperglycemia. Hypoglycemia exacerbated the neurochemical changes in cerebral cortex induced by hyperglycemia. These findings have implications for both therapy and identification of causes contributing to neuronal dysfunction in diabetes. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Niosomes of Ascorbic Acid and α-Tocopherol in the Cerebral Ischemia-Reperfusion Model in Male Rats

    Directory of Open Access Journals (Sweden)

    Jaleh Varshosaz

    2014-01-01

    Full Text Available The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neuroprotective effect against cerebral ischemia. Neuronal damage was evaluated by optical microscopy and transmission electron microscopy. The encapsulation efficiency of ascorbic acid was increased to more than 84% by remote loading method. The cholesterol content of the niosomes, the hydrophilicity potential of the encapsulated compounds, and the preparation method of niosomes were the main factors affecting the mean volume diameter of the prepared vesicles. High physical stability of the niosomes prepared from Span 40 and Span 60 was demonstrated due to negligible size change of vesicles during 6 months storage at 4–8°C. In vivo studies showed that ST60/Chol 35 : 35 : 30 niosomes had more neuroprotective effects against cerebral ischemic injuries in male rats than free ascorbic acid.

  17. Niosomes of ascorbic acid and α-tocopherol in the cerebral ischemia-reperfusion model in male rats.

    Science.gov (United States)

    Varshosaz, Jaleh; Taymouri, Somayeh; Pardakhty, Abbas; Asadi-Shekaari, Majid; Babaee, Abodolreza

    2014-01-01

    The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neuroprotective effect against cerebral ischemia. Neuronal damage was evaluated by optical microscopy and transmission electron microscopy. The encapsulation efficiency of ascorbic acid was increased to more than 84% by remote loading method. The cholesterol content of the niosomes, the hydrophilicity potential of the encapsulated compounds, and the preparation method of niosomes were the main factors affecting the mean volume diameter of the prepared vesicles. High physical stability of the niosomes prepared from Span 40 and Span 60 was demonstrated due to negligible size change of vesicles during 6 months storage at 4-8(°)C. In vivo studies showed that ST60/Chol 35 : 35 : 30 niosomes had more neuroprotective effects against cerebral ischemic injuries in male rats than free ascorbic acid.

  18. Effects of Cortical Spreading Depression on Synaptic Activity, Blood Flow and Oxygen Consumption in Rat Cerebral Cortex

    DEFF Research Database (Denmark)

    Hansen, Henning Piilgaard

    2010-01-01

    As the title of this thesis indicates I have during my PhD studied the effects of cortical spreading depression (CSD) on synaptic activity, blood flow and oxygen consumption in rat cerebral cortex. This was performed in vivo using an open cranial window approach in anesthetized rats. I applied...... parameters of the whisker/infraorbital nerve etwork (IO) targeting the same cortical area. We tested the hypothesis that the relation between increases in CBF and CMRO2 evoked by stimulation and synaptic activity differed for the two activated networks and that activation of two distinct networks activate...

  19. Isquemia cerebral focal transitoria en rata: caracterización y utilidad del modelo de la sutura intraluminal en el estudio de estrategias neuroprotectoras

    OpenAIRE

    Pérez Asensio, Fernando Jesús

    2005-01-01

    RESUMEN Los accidentes cerebrovasculares agudos (ictus cerebrales) son trastornos neurológicos originados por la disminución brusca del aporte sanguíneo cerebral (isquemia cerebral). La incidencia del ictus en España es de unos 200 casos por cada 100.000 habitantes, lo que le sitúa como la segunda causa de muerte, la primera de invalidez permanente y segunda de demencia. A excepción de la aplicación de la terapia trombolítica, actualmente no existe otro tratamiento eficaz del ictus en c...

  20. Protective Effects and Mechanism of Puerarin on Learning-Memory Disorder after Global Cerebral Ischemia-Reperfusion Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    WU Hai-qin; GUO He-na; WANG Hu-qing; CHANG Ming-ze; ZHANG Gui-lian; ZHAO Ying-xian

    2009-01-01

    Objective: To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action. Methods: The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively. Results: (1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged significantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the pueradn group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the pueradn group was up-regulated at the respective time points after ischemia raperfusion (P<0.01), reaching the peak on day 1. Conclusions: Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.

  1. Electroacupuncture-Induced Neuroprotection against Cerebral Ischemia in Rats: Role of the Dopamine D2 Receptor

    Directory of Open Access Journals (Sweden)

    Ming-Shu Xu

    2013-01-01

    Full Text Available Background. Cerebral ischemia is known to produce brain damage and related behavioural deficits, including memory deficits and motor disorders. Evidence shows that EA significantly promotes recovery of neurological function and thus improves quality of life. Objective. Evidence exists for the involvement of catecholamines in human neuroplasticity. A better understanding of dopaminergic (DAergic modulation in this process will be important. Methods. A total of 72 adult male Sprague-Dawley (SD rats were divided into 6 groups: normal, model, EA, spiperone group, EA + spiperone group, and pergolide. The middle cerebral artery occlusion (MCAO model was used in all 6 groups except the normal group. A behavioural assessment was conducted at 1, 3, 5, and 7 days after MCAO. The percent of brain infarct area was also determined 7 days after MCAO. Tyrosine hydroxylase (TH and growth-associated protein 43 (GAP-43 fluorescence double labeling was performed in the striatum. Results. In this study, we found that EA at Fengchi (GB20 acupoints resulted in marked improvements based on a behavioural assessment. Both TTC staining and GAP-43 immunofluorescence labeling results showed that EA treatment reduced ischemia injury and promoted neuroplasticity compared with the model group. The D2R-selective agonist, pergolide, showed similar results, but these results were reversed by the D2R-selective antagonist, spiperone. We also found that there were more colocalization and expression of GAP-43 and TH in the EA and pergolide groups than those in the other groups. Conclusion. These results suggest that the neuroplasticity induced by EA was mediated by D2 autoreceptors in DAergic neurons.

  2. Xinnao Shutong Modulates the Neuronal Plasticity Through Regulation of Microglia/Macrophage Polarization Following Chronic Cerebral Hypoperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Liye Wang

    2018-05-01

    Full Text Available Xinnao shutong (XNST capsules have been clinically used in China to treat cerebrovascular diseases. Previous studies have demonstrated that XNST has significant neuroprotective effects against acute cerebral ischemic stroke. The present study investigated the effects and mechanisms of XNST treatment following chronic cerebral hypoperfusion. Thirty-six adult male Sprague-Dawley rats were treated with XNST or vehicle following permanent bilateral common carotid artery (BCCA ligation. Body weight was recorded on days 0, 3, 7, 14, 28, and 42 post-surgery. The Morris water maze (MWM test was used to assess cognitive function in rats. Immunofluorescent staining and western blot were used to assess the severity of neuronal plasticity, white matter injury, and the numbers and/or phenotypic changes incurred to microglia. Protein levels of p-AKT (Thr308 and p-ERK (Thr202/Tyr204 were detected 42 days after BCCA ligation was performed. The results indicate that XNST treatment significantly reduced escape latency, decreased the frequency of platform crossing compared to the vehicle group. Synaptophysin, protein levels improved and white matter injury ameliorated following XNST treatment. Meanwhile, XNST reduced the number of M1 microglia and increased the number of M2 microglia. Furthermore, p-AKT (Thr308 and p-ERK (Thr202/Tyr204 levels were increased 42 days following BCCA ligation. In summary, our results suggest that XNST mitigates memory impairments by restoration of neuronal plasticity and by modulation of microglial polarization following chronic cerebral hypoperfusion in rats.

  3. Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia.

    Science.gov (United States)

    Rojas, Santiago; Herance, José Raul; Abad, Sergio; Jiménez, Xavier; Pareto, Deborah; Ruiz, Alba; Torrent, Èlia; Figueiras, Francisca P; Popota, Foteini; Fernández-Soriano, Francisco J; Planas, Anna M; Gispert, Juan D

    2011-06-01

    [¹⁸F]Fluoromisonidazole (¹⁸F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of ¹⁸F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes. Rats (n = 14) were subjected to permanent ischemia by intraluminal occlusion of the middle cerebral artery in order to assess by PET the uptake of ¹⁸F-FMISO at various times over 24 h following ischemia. The PET results were compared to histological changes with Nissl and 2,3,5 triphenyltetrazolium chloride staining. Elevated uptake of ¹⁸F-FMISO was detected in the infarcted area up to 8 h after occlusion but was no longer detected at 24 h, a time point coincident with pan necrosis of the tissue. Our findings suggest that salvageable tissue persists for up to 8 h in this rat model of brain ischemia. We propose ¹⁸F-FMISO PET as a tool for evaluating the ischemic penumbra after cerebral ischemia.

  4. [Effects of combined use of total alkaloids of Uncaria rhynchophylla and Coryadlis ambailis migo on cerebral ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Hu, Xue-yong; Sun, An-sheng; Sui, Yu-xia

    2007-11-01

    To study the effects of combined use of total alkaloids (TA) of Uncaria rhynchophylla (UR) and Coryadlis ambailis migo (CAM) on cerebral ischemia/reperfusion injury in rats. Rat model of middle cerebral artery ischemia/reperfusion was established, the changes of neurological state was scored before and after treatment with the two kinds of TA, single or combined, and the changes of cerebral infarcted volume, cerebral water content, activities of NOS and SOD and content of MDA in rats' brain were estimated as well. After being treated with the combination of both TA, the average neurological score, cerebral infracted volume, cerebral water content, activity of NOS and content of MDA in the model rats significantly decreased, and the activity of SOD was significantly increased (all P < 0.05). The effect of combined use of the two TA was higher than that of use TA of UR or CAM alone (P <0.05). Moreover, the central nervous system inhibitory effect induced by combined TA was significantly weaker than that of UR. Combined use of TA of UR and CAM may facilitate the protection against cerebral ischemia/reperfusion damage, the action mechanism might be relevant to reducing the lipid peroxidation injury of brain cells through inhibiting the NOS activity and increasing the SOD activity.

  5. Focal myositis

    Energy Technology Data Exchange (ETDEWEB)

    Kransdorf, M.J. [Saint Mary`s Hospital, Richmond, VA (United States). Dept. of Radiol.]|[Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Temple, H.T. [Department of Orthopedic Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia (United States)]|[Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Sweet, D.E. [Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States)

    1998-05-01

    Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.) With 3 figs., 25 refs.

  6. Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex

    International Nuclear Information System (INIS)

    Guo, Bao-Qiang; Yan, Chong-Huai; Cai, Shi-Zhong; Yuan, Xiao-Bing; Shen, Xiao-Ming

    2013-01-01

    Highlights: ► Low level MeHg exposure causes migratory defect of rat cerebrocortical neurons. ► The migration defect is due to the impact of MeHg on the neuronal migration itself. ► Rho GTPases seem to be involved in MeHg-induced disruption of neuronal migration. -- Abstract: We determined the effects of low-level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation. We used offspring rats born to dams that had been exposed to saline or various doses of MeHg (0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day) from gestational day (GD) 11–21. Immunohistochemical examination of the brains of the offspring was conducted on postnatal day (PND) 0, PND3, and PND7. Our results showed that prenatal exposure to low levels of MeHg (0.1 mg/kg/day or 1 mg/kg/day) during the critical stage in neuronal migration resulted in migration defects of the cerebrocortical neurons in offspring rats. Importantly, our data revealed that the abnormal neuronal distribution induced by MeHg was not caused by altered proliferation of neural progenitor cells (NPCs), induction of apoptosis of NPCs and/or newborn neurons, abnormal differentiation of NPCs, and the morphological changes of radial glial scaffold, indicating that the defective neuronal positioning triggered by exposure to low-dose of MeHg is due to the impacts of MeHg on the process of neuronal migration itself. Moreover, we demonstrated that in utero exposure to low-level MeHg suppresses the expression of Rac1, Cdc42, and RhoA, which play key roles in the migration of cerebrocortical neurons during the early stage of brain development, suggesting that the MeHg-induced migratory disturbance of cerebrocortical neurons is likely associated with the Rho GTPases signal pathway. In conclusion, our results provide a novel perspective on clarifying the mechanisms underlying the impairment of neuronal migration induced by MeHg

  7. Trigeminal nociception-induced, cerebral Fos expression in the conscious rat

    NARCIS (Netherlands)

    Ter Horst, GJ; Meijler, WJ; Korf, J; Kemper, RHA

    2001-01-01

    Little is known about trigeminal nociception-induced cerebral activity and involvement of cerebral structures in pathogenesis of trigeminovascular headaches such as migraine. Neuroimaging has demonstrated cortical, hypothalamic and brainstem activation during the attack and after abolition with

  8. Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

    International Nuclear Information System (INIS)

    Silva, J.E.; Matthews, P.S.

    1984-01-01

    Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum, cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats

  9. Histological evidence for drug diffusion across the cerebral meninges into the underlying neocortex in rats.

    Science.gov (United States)

    Ludvig, Nandor; Sheffield, Lynette G; Tang, Hai M; Baptiste, Shirn L; Devinsky, Orrin; Kuzniecky, Ruben I

    2008-01-10

    Transmeningeal pharmacotherapy has been proposed to treat neurological disorders with localized pathology, such as intractable focal epilepsy. As a step toward understanding the diffusion and intracortical spread of transmeningeally delivered drugs, the present study used histological methods to determine the extent to which a marker compound, N-methyl-D-aspartate (NMDA), can diffuse into the neocortex through the meninges. Rats were implanted with bilateral parietal cortical epidural cups filled with 50 mM NMDA on the right side and artificial cerebrospinal fluid (ACSF) in the contralateral side. After 24 h, the histological effects of these treatments were evaluated using cresyl violet (Nissl) staining. The epidural NMDA exposure caused neuronal loss that in most animals extended from the pial surface through layer V. The area indicated by this neuronal loss was localized to the neocortical region underlying the epidural cup. These results suggest that NMDA-like, water soluble, small molecules can diffuse through the subdural/subarachnoid space into the underlying neocortex and spread in a limited fashion, close to the meningeal penetration site.

  10. Proteomic profiling of the rat cerebral cortex in sleep and waking.

    Science.gov (United States)

    Cirelli, C; Pfister-Genskow, M; McCarthy, D; Woodbury, R; Tononi, G

    2009-09-01

    Transcriptomic studies have shown that hundreds of genes change their expression levels across the sleep/waking cycle, and found that waking-related and sleep-related mRNAs belong to different functional categories. Proteins, however, rather than DNA or RNA, carry out most of the cellular functions, and direct measurements of protein levels and activity are required to assess the effects of behavioral states on the overall functional state of the cell. Here we used surface-enhanced laser desorption-ionization (SELDI), followed by time-of-flight mass spectrometry, to obtain a large-scale profiling of the proteins in the rat cerebral cortex whose expression is affected by sleep, spontaneous waking, short (6 hours) and long (7 days) sleep deprivation. Each of the 94 cortical samples was profiled in duplicate on 4 different ProteinChip Array surfaces using 2 different matrix molecules. Overall, 1055 protein peaks were consistently detected in cortical samples and 15 candidate biomarkers were selected for identification based on significant changes in multiple conditions (conjunction analysis): 8 "sleep" peaks, 4 "waking" peaks, and 4 "long sleep deprivation" peaks. Four candidate biomarkers were purified and positively identified. The 3353 Da candidate sleep marker was identified as the 30 amino acid C-terminal fragment of rat histone H4. This region encompasses the osteogenic growth peptide, but a possible link between sleep and this peptide remains highly speculative. Two peaks associated with short and long sleep deprivation were identified as hemoglobin alpha1/2 and beta, respectively, while another peak associated with long sleep deprivation was identified as cytochrome C. The upregulation of hemoglobins and cytochrome C may be part of a cellular stress response triggered by even short periods of sleep loss.

  11. Estimating blood and brain concentrations and blood-to-brain influx by magnetic resonance imaging with step-down infusion of Gd-DTPA in focal transient cerebral ischemia and confirmation by quantitative autoradiography with Gd-[14C]DTPA

    OpenAIRE

    Knight, Robert A; Karki, Kishor; Ewing, James R; Divine, George W; Fenstermacher, Joseph D; Patlak, Clifford S; Nagaraja, Tavarekere N

    2009-01-01

    An intravenous step-down infusion procedure that maintained a constant gadolinium-diethylene-triaminepentaacetic acid (Gd-DTPA) blood concentration and magnetic resonance imaging (MRI) were used to localize and quantify the blood–brain barrier (BBB) opening in a rat model of transient cerebral ischemia (n = 7). Blood-to-brain influx rate constant (Ki) values of Gd-DTPA from such regions were estimated using MRI–Patlak plots and compared with the Ki values of Gd-[14C]DTPA, determined minutes l...

  12. Expression of S100 protein and protective effect of arundic acid on the rat brain in chronic cerebral hypoperfusion.

    Science.gov (United States)

    Ohtani, Ryo; Tomimoto, Hidekazu; Wakita, Hideaki; Kitaguchi, Hiroshi; Nakaji, Kayoko; Takahashi, Ryosuke

    2007-03-02

    S100 protein is expressed primarily by astroglia in the brain, and accumulates in and around the ischemic lesions. Arundic acid, a novel astroglia-modulating agent, is neuroprotective in acute cerebral infarction, whereas the protective effects remain unknown during chronic cerebral hypoperfusion. Rats undergoing chronic cerebral hypoperfusion were subjected to a bilateral ligation of the common carotid arteries, and were allowed to survive for 3, 7 and 14 days. The animals received a daily intraperitoneal injection of 5.0, 10.0 or 20.0 mg/kg of arundic acid, or vehicle, for 14 days. Alternatively, other groups of rats received a delayed intraperitoneal injection of 20.0 mg/kg of arundic acid or vehicle, which started from 1, 3 or 7 days after ligation and continued to 14 days. The degree of white matter (WM) lesions and the numerical density of S100 protein-immunoreactive astroglia were estimated. In the WM of rats with vehicle injections, the number of S100 protein-immunoreactive astroglia increased significantly after chronic cerebral hypoperfusion as compared to the sham-operation. A dosage of 10.0 and 20.0 mg/kg of arundic acid suppressed the numerical increase in S100 protein-immunoreactive astroglia and the WM lesions. These pathological changes were suppressed with delayed treatment up to 7 days in terms of astroglial activation, and up to 3 days in terms of the WM lesions. The protective effects of arundic acid against WM lesions were demonstrated in a dose-dependent manner, and even after postischemic treatments. These results suggest the potential usefulness of arundic acid in the treatment of cerebrovascular WM lesions.

  13. Actions of the pyrethroid insecticide bifenthrin on sodium channels expressed in rat cerebral cortical neurons.

    Science.gov (United States)

    Yang, Lin; Li, Li

    2015-01-01

    Voltage-gated sodium channels are important sites for the neurotoxic actions of pyrethroid insecticides in mammals. Here, we studied the mode of action of bifenthrin on the native sodium channels in cerebral cortical neurons prepared from newborn rat brain, where the toxic effects are largely generated. Bifenthrin caused a pronounced late current that persisted at the end of a depolarizing pulse, a slowly-decaying tail current following repolarization and significant resting modification (25.3% modification at 10 μM). No significant bifenthrin-induced effect was observed at the peak current. Bifenthrin also caused a concentration-dependent hyperpolarizing shift in steady-state activation and inactivation as well as slowed recovery from channel inactivation. Repetitive depolarization increased the potency of bifenthrin with high frequency. There was approximately 64% inhibition of modification upon repetitive activation by 10-Hz trains of depolarizing pulses. These results suggest that bifenthrin binds to and modifies sodium channels in both the closed and open states and exhibits the behavior between type I and type II.

  14. Neuroprotective effect of Buddleja officinalis extract on transient middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Lee, Dae-Hee; Ha, Nina; Bu, Yung-Min; Choi, Hyoung Il; Park, Yoo Guen; Kim, Yoon Bum; Kim, Mi-Yeon; Kim, Hocheol

    2006-08-01

    The flower buds of Buddleja officinalis MAXIM (Loganiaceae) are used to treat headache and inflammatory diseases in traditional Korean medicine. In the present study, the neuroprotective effects of the methanolic extract of B. officinalis (BOME) and of its hexane fraction (BOHF) were investigated in a middle cerebral artery occlusion (MCAo, 120 min occlusion, 24 h reperfusion) Sprague-Dawley rat model. BOME or BOHF (100 mg/kg, p.o.) was twice administered 30 min before the onset of MCAo and 2 h after reperfusion. BOME and BOHF treated groups showed infarct volumes reduced by 33.9% and 68.2%, respectively, at 2 h occlusion. In BOHF treated animals, cyclooxygenase-2 and iNOS inductions were inhibited in ischemic hemispheres at both the mRNA and protein levels. Furthermore, in vitro studies showed that BOME and BOHF both inhibited LPS-induced nitric oxide production in BV-2 mouse microglial cells. These results suggest that the anti-inflammatory and the microglial activation inhibitory effects of B. officinalis extract may contribute to its neuroprotective effects in brain ischemia.

  15. In vivo transgenic expression of collybistin in neurons of the rat cerebral cortex.

    Science.gov (United States)

    Fekete, Christopher D; Goz, Roman U; Dinallo, Sean; Miralles, Celia P; Chiou, Tzu-Ting; Bear, John; Fiondella, Christopher G; LoTurco, Joseph J; De Blas, Angel L

    2017-04-01

    Collybistin (CB) is a guanine nucleotide exchange factor selectively localized to γ-aminobutyric acid (GABA)ergic and glycinergic postsynapses. Active CB interacts with gephyrin, inducing the submembranous clustering and the postsynaptic accumulation of gephyrin, which is a scaffold protein that recruits GABA A receptors (GABA A Rs) at the postsynapse. CB is expressed with or without a src homology 3 (SH3) domain. We have previously reported the effects on GABAergic synapses of the acute overexpression of CB SH3- or CB SH3+ in cultured hippocampal (HP) neurons. In the present communication, we are studying the effects on GABAergic synapses after chronic in vivo transgenic expression of CB2 SH3- or CB2 SH3+ in neurons of the adult rat cerebral cortex. The embryonic precursors of these cortical neurons were in utero electroporated with CB SH3- or CB SH3+ DNAs, migrated to the appropriate cortical layer, and became integrated in cortical circuits. The results show that: 1) the strength of inhibitory synapses in vivo can be enhanced by increasing the expression of CB in neurons; and 2) there are significant differences in the results between in vivo and in culture studies. J. Comp. Neurol. 525:1291-1311, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Effect of certain antioxidants on cerebral ischemia induced in irradiated rats

    International Nuclear Information System (INIS)

    Abd El-Aziz, E.R.

    2008-01-01

    The present study was performed to investigate the possible roles of vitamin E, coenzyme-Q 10 and rutin in ameliorating the biochemical changes in the brain and serum induced by cerebral ischemia/reperfusion (I/R) in rats exposed to whole body gamma radiation. Induction of I/R increased the brain oxidative stress as manifested by a marked increase in its content of MDA accompanied by depletion of its GSH content, and a compensatory elevation in the cytosolic activities of GPx and GR enzymes. In addition, it caused a significant rise in brain cytosolic activity of LDH and cytosolic Ca 2+ level. Furthermore, I/R provoked a remarkable inflammatory response reflected by the observed significant increment in serum levels of the pro inflammatory cytokines TNF-α and IL-Iβ. Moreover, induction of I/R in fractionally or single irradiated rats resulted in a further increase in brain oxidative stress and cytosolic LDH activity, disturbed brain Ca 2+ homeostasis, as well as an exaggerated inflammatory reaction. Concomitant to radiation, daily administration of each of vitamin E, coenzyme-Q 10 and rutin to irradiated rats before induction of I/R, was effective in alleviating the brain oxidative stress (represented by a decrease in the increment of brain MDA concentration and the restoration of its GSH level). Moreover, each of these antioxidants caused a significant attenuation of the compensatory rise of the cytosolic activities of GPx and GR enzymes. Antioxidants were, also; able to partially correct the metabolic disturbances induced in brain by I/R and radiation, that correction was reflected by lowering of the cytosolic LDH activity and Ca 2+ level. Administration of each of vitamin E and rutin revealed a potent ant inflammatory action of these antioxidants, while coenzyme-Q 10 had no significant effect on serum levels of TNF-α and IL-Iβ. Finally, the present study justifies the use of antioxidants in hope to alleviate or minimize the various deleterious effects of

  17. Effect of certain antioxidants on cerebral ischemia induced in irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Abd El-Aziz, E R [National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo (Egypt)

    2008-07-01

    The present study was performed to investigate the possible roles of vitamin E, coenzyme-Q{sub 10} and rutin in ameliorating the biochemical changes in the brain and serum induced by cerebral ischemia/reperfusion (I/R) in rats exposed to whole body gamma radiation. Induction of I/R increased the brain oxidative stress as manifested by a marked increase in its content of MDA accompanied by depletion of its GSH content, and a compensatory elevation in the cytosolic activities of GPx and GR enzymes. In addition, it caused a significant rise in brain cytosolic activity of LDH and cytosolic Ca{sup 2+} level. Furthermore, I/R provoked a remarkable inflammatory response reflected by the observed significant increment in serum levels of the pro inflammatory cytokines TNF-{alpha} and IL-I{beta}. Moreover, induction of I/R in fractionally or single irradiated rats resulted in a further increase in brain oxidative stress and cytosolic LDH activity, disturbed brain Ca{sup 2+} homeostasis, as well as an exaggerated inflammatory reaction. Concomitant to radiation, daily administration of each of vitamin E, coenzyme-Q{sub 10} and rutin to irradiated rats before induction of I/R, was effective in alleviating the brain oxidative stress (represented by a decrease in the increment of brain MDA concentration and the restoration of its GSH level). Moreover, each of these antioxidants caused a significant attenuation of the compensatory rise of the cytosolic activities of GPx and GR enzymes. Antioxidants were, also; able to partially correct the metabolic disturbances induced in brain by I/R and radiation, that correction was reflected by lowering of the cytosolic LDH activity and Ca{sup 2+} level. Administration of each of vitamin E and rutin revealed a potent ant inflammatory action of these antioxidants, while coenzyme-Q{sub 10} had no significant effect on serum levels of TNF-{alpha} and IL-I{beta}. Finally, the present study justifies the use of antioxidants in hope to alleviate or

  18. The rate of cerebral utilization of glucose, ketone bodies, and oxygen: a comparative in vivo study of infant and adult rats.

    Science.gov (United States)

    Dahlquist, G; Persson, B

    1976-11-01

    Cerebral blood flow (CBF) was measured by means of Celabeled microspheres in infant (20-day-old) and adult (3-month-old) rats, anesthetised with Na-5-ethyl-5-(1-methylpropyl)2-thiobarbituric acid. Cerebral arteriovenous differences of acetoacetate, D-beta-hydroxybutyrate, glucose, lactate, and oxygen and brain DNA content were determined in other groups of similarly treated infant and adult animals fed or starved for 48 or 72 hr. The mean CBF values of 0.48+/-0.04 and 0.62+/-0.07 ml/(g X min), +/- SEM, in infant and adult animals, respectively, were not significantly different. CBF was unaffected by starvation. At any given arterial concentration the cerebral arteriovenous difference of acetoacetate was significantly higher in infant than adult rats. The same was true for D-beta-hydroxybutyrate at arterial concentrations above 1 mmol/liter. There was an approximately linear relationship between arterial concentration of acetoacetate and its cerebral arteriovenous difference in both infant and adult rats. A similar relationship was found for D-beta-hydroxybutyrate only in infant animals. In the fed state, the cerebral uptake of glucose and ketone bodies (micromoles per (mg DNA X min)) was not different in infant and adult rats. During starvation, cerebral uptake of ketone bodies expressed as micromoles per (mg DNA X min) was higher in infant than adult rats, indicating a higher rate of utilization of ketone bodies per cell in these animals. For glucose, no such difference was found in either fed or starved groups (Table 3). The average percentage of the total cerebral uptake of substrates (micromoles per min) accounted for by ketone bodies increased in both infant and adult rats during starvation. This percentage value was clearly higher in infant than adult rats during starvation. After 72 hr of starvation the values were 38.8% and 15.2% in infant and adult rats, respectively (Fig. 3). Calculated cerebral metabolic rate for oxygen (CMRO2), assuming complete

  19. [Effect of Tongluo Xingnao effervescent tablets on learning and memory dysfunction in rats with chronic cerebral ischemia].

    Science.gov (United States)

    Hu, Yong; Ju, Shao-Hua; Zhang, Yin-Jie; Xiong, Min; Xu, Shi-Jun; Ma, Yun-Tong; Zhong, Zhen-Dong

    2014-05-01

    To study the effect of Tongluo Xingnao effervescent tablets on learning and memory capacity and expression of Na(+)-K(+)-ATPase in hippocampus of rats with chronic cerebral ischemia-induced learning and memory dysfunction model. The 2-VO method was used to establish sd rat model learning and memory dysfunction induced by chronic cerebral ischemia. The 50 rats in the successfully established model were randomly divided into the model control group, the Dihydroergotoxine Mesylate tablets group (0.7 mg x kg(-1), Tongluo Xingnao effervescent tablets high dose (7.56 g x kg(-1)), middle dose (3.78 g x kg(-1)) and low dose (1.59 g x kg(-1)) groups and the sham operation group (n = 10) as the control group. The groups were orally given 10 ml x kg(-1) x d(-1) drugs for consecutively 90 days. On the 86th day, Morris water maze was adopted for them. On the 90th day, a leaning and memory capacity test was held. The brain tissues were fixed with 10% formaldehyde and observed for pathomorphism after routine slide preparation and staining. The expression of hippocampal Na(+)-K(+)-ATPase was detected with immunohistochemistry and image quantitative analysis. Compared with the model group, all of Tongluo Xingnao effervescent tablets groups showed significant decrease in the escape latency at the 5th day in the Morris water maze, and notable increase in the frequency of the first quadrant dwell, the frequency passing the escape platform and the frequency entering effective area (p tablets can improve the learning and memory capacity, reduce pathological changes of hippocampal tissues of rats with chronic cerebral ischemia-induced learning and memory dysfunction model, and promote the expression of Na(+)-K(+)-ATPase in hippocampus.

  20. Mechanics and composition of middle cerebral arteries from simulated microgravity rats with and without 1-h/d -Gx gravitation.

    Directory of Open Access Journals (Sweden)

    Jiu-Hua Cheng

    Full Text Available BACKGROUND: To elucidate further from the biomechanical aspect whether microgravity-induced cerebral vascular mal-adaptation might be a contributing factor to postflight orthostatic intolerance and the underlying mechanism accounting for the potential effectiveness of intermittent artificial gravity (IAG in preventing this adverse effect. METHODOLOGY/PRINCIPAL FINDINGS: Middle cerebral arteries (MCAs were isolated from 28-day SUS (tail-suspended, head-down tilt rats to simulate microgravity effect, S+D (SUS plus 1-h/d -Gx gravitation by normal standing to simulate IAG, and CON (control rats. Vascular myogenic reactivity and circumferential stress-strain and axial force-pressure relationships and overall stiffness were examined using pressure arteriography and calculated. Acellular matrix components were quantified by electron microscopy. The results demonstrate that myogenic reactivity is susceptible to previous pressure-induced, serial constrictions. During the first-run of pressure increments, active MCAs from SUS rats can strongly stiffen their wall and maintain the vessels at very low strains, which can be prevented by the simulated IAG countermeasure. The strains are 0.03 and 0.14 respectively for SUS and S+D, while circumferential stress being kept at 0.5 (106 dyn/cm2. During the second-run pressure steps, both the myogenic reactivity and active stiffness of the three groups declined. The distensibility of passive MCAs from S+D is significantly higher than CON and SUS, which may help to attenuate the vasodilatation impairment at low levels of pressure. Collagen and elastin percentages were increased and decreased, respectively, in MCAs from SUS and S+D as compared with CON; however, elastin was higher in S+D than SUS rats. CONCLUSIONS: Susceptibility to previous myogenic constrictions seems to be a self-limiting protective mechanism in cerebral small resistance arteries to prevent undue cerebral vasoconstriction during orthostasis at 1-G

  1. Effect of ligustrazine on levels of amino acid neurotransmitters in rat striatum after cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Han, Jin; Wan, Hai-Tong; Yang, Jie-Hong; Zhang, Yu-Yan; Ge, Li-Jun; Bie, Xiao-Dong

    2014-01-01

    This study aimed to evaluate the effect of ligustrazine on levels of amino acid transmitters in the extracellular fluid of striatum following cerebral ischemia/reperfusion (I/R) in male Sprague-Dawley rats. A microdialysis cannula guide was implanted into the right striatum. After recovery, animals underwent a sham operation or middle cerebral artery occlusion (MCAO). Those that developed cerebral ischemia after MCAO were randomized to receive propylene glycol salt water and ligustrazine respectively. Striatal fluid samples were collected from all animals at 15-min intervals after treatment and were subjected to HPLC analysis of aspartic acid, glutamic acid, taurine, and γ-amino butyric acid. Upon the last sample collection, animals were sacrificed and brain tissue specimens were collected for triphenyltetrazolium chloride staining and NeuN staining. Compared with the sham operation, MCAO induced significant neurological deficits and increased striatal concentrations of the four neurotransmitters assessed in a time-dependent manner (P cerebral infarction-protective agent may have potential clinical implications for I/R-related brain damage.

  2. Valor localizador y lateralizador de la manifestación motora facial unilateral en epilepsias focales, utilizando VEEG y/o estimulación cortical directa cerebral

    Directory of Open Access Journals (Sweden)

    Natalia Paoli

    2014-07-01

    Full Text Available Las manifestaciones motoras faciales unilaterales (MMFU se describen clásicamente en crisis que inician en la región central inferior contralateral. Para evaluar el valor localizador y lateralizador de MMFU en crisis espontáneas registradas en videoelectroencefalografía (VEEG y de MMFU obtenidas por estimulación cortical directa cerebral, analizamos 83 crisis con MMFU durante VEEG y 8 pacientes que presentaron MMFU durante estimulación cortical directa cerebral. Correlacionamos localización y lateralidad de la hipótesis de zona epileptógena con el tiempo de aparición  de MMFU, y la zona de estimulación cortical directa cerebral que desencadenó MMFU con su lateralidad. En 61 crisis con MMFU (73.4% la hipótesis de zona epileptógena no correspondió a la región central contralateral, por corresponder a la región central ipsilateral o a otras regiones tanto homolaterales como contralaterales. La MMFU se registró en forma precoz en 51.1% de las crisis con hipótesis de zona epileptógena en la región frontal, en  56% de las crisis con hipótesis de zona epileptógena en la región central y en 80% de las crisis con hipótesis de zona epileptógena en el lóbulo temporal. No registramos MMFU precoz  en las crisis con hipótesis de zona epileptógena en la región posterior. En 2 (25% de 8 pacientes con MMFU provocada por estimulación cortical directa cerebral, la zona de la estimulación no fue la región central inferior contralateral. Concluimos que las MMFU pueden deberse a descargas alejadas de la región central inferior, tanto ipsilaterales como contralaterales.

  3. La atorvastatina protege las neuronas gabérgicas y dopaminérgicas del sistema nigroestriatal en un modelo experimental de isquemia cerebral focal transitoria en ratas

    OpenAIRE

    Angélica María Sabogal; Cesar Augusto Arango; Gloria Patricia Cardona; Ángel Enrique Céspedes

    2014-01-01

    Introducción. La isquemia cerebral es la tercera causa de muerte y la primera de discapacidad permanente en el mundo. La atorvastatina es un fármaco neuroprotector prometedor para el tratamiento de la apoplejía; sin embargo, su acción sobre las poblaciones neuronales del sistema nigroestriatal después de la isquemia aún se desconoce. Objetivo. Evaluar el efecto de la atorvastatina sobre poblaciones gabérgicas y dopaminérgicas en regiones exofocales en un modelo de oclusión transitoria de ...

  4. A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion

    Science.gov (United States)

    Mitsios, Nick; Saka, Mohamad; Krupinski, Jerzy; Pennucci, Roberta; Sanfeliu, Coral; Wang, Qiuyu; Rubio, Francisco; Gaffney, John; Kumar, Pat; Kumar, Shant; Sullivan, Matthew; Slevin, Mark

    2007-01-01

    Background Altered gene expression is an important feature of ischemic cerebral injury and affects proteins of many functional classes. We have used microarrays to investigate the changes in gene expression at various times after middle cerebral artery occlusion in human and rat brain. Results Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases. The total number of deregulated genes in the rat was 335 versus 126 in the human, while, of 393 overlapping genes between the two array sets, 184 were changed only in the rat and 36 in the human with a total of 41 genes deregulated in both cases. Interestingly, the mean fold changes were much higher in the human. The expression of novel genes, including p21-activated kinase 1 (PAK1), matrix metalloproteinase 11 (MMP11) and integrase interactor 1, was further analyzed by RT-PCR, Western blotting and immunohistochemistry. Strong neuronal staining was seen for PAK1 and MMP11. Conclusion Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents. PMID:17997827

  5. Identification of proteins regulated by curcumin in cerebral ischemia.

    Science.gov (United States)

    Shah, Fawad-Ali; Gim, Sang-Ah; Sung, Jin-Hee; Jeon, Seong-Jun; Kim, Myeong-Ok; Koh, Phil-Ok

    2016-03-01

    Curcumin is known to have a neuroprotective effect against cerebral ischemia. The objective of this study was to identify various proteins that are differentially expressed by curcumin treatment in focal cerebral ischemia using a proteomic approach. Adult male rats were treated with vehicle or curcumin 1 h after middle cerebral artery occlusion. Brain tissues were collected 24 h after the onset of middle cerebral artery occlusion, and cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry. We detected several proteins with altered expression levels between vehicle- and curcumin-treated animals. Among these proteins, ubiquitin carboxy-terminal hydrolase L1, isocitrate dehydrogenase, adenosylhomocysteinase, and eukaryotic initiation factor 4A were decreased in the vehicle-treated animal, and curcumin treatment attenuated the injury-induced decreases of these proteins. Conversely, pyridoxal phosphate phosphatase was increased in the vehicle-treated animal, and curcumin treatment prevented decreases in this protein. The identified altered proteins are associated with cellular metabolism and differentiation. The results of this study suggest that curcumin exerts a neuroprotective effect by regulating the expression of various proteins in focal cerebral ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Cerebral changes occurring in arginase and dimethylarginine dimethylaminohydrolase (DDAH in a rat model of sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Donia Amrouni

    2011-03-01

    Full Text Available Involvement of nitric oxide (NO in the pathophysiology of human African trypanosomiasis (HAT was analyzed in a HAT animal model (rat infected with Trypanosoma brucei brucei. With this model, it was previously reported that trypanosomes were capable of limiting trypanocidal properties carried by NO by decreasing its blood concentration. It was also observed that brain NO concentration, contrary to blood, increases throughout the infection process. The present approach analyses the brain impairments occurring in the regulations exerted by arginase and N(G, N(G-dimethylarginine dimethylaminohydrolase (DDAH on NO Synthases (NOS. In this respect: (i cerebral enzymatic activities, mRNA and protein expression of arginase and DDAH were determined; (ii immunohistochemical distribution and morphometric parameters of cells expressing DDAH-1 and DDAH-2 isoforms were examined within the diencephalon; (iii amino acid profiles relating to NOS/arginase/DDAH pathways were established.Arginase and DDAH activities together with mRNA (RT-PCR and protein (western-blot expressions were determined in diencephalic brain structures of healthy or infected rats at various days post-infection (D5, D10, D16, D22. While arginase activity remained constant, that of DDAH increased at D10 (+65% and D16 (+51% in agreement with western-blot and amino acids data (liquid chromatography tandem-mass spectrometry. Only DDAH-2 isoform appeared to be up-regulated at the transcriptional level throughout the infection process. Immunohistochemical staining further revealed that DDAH-1 and DDAH-2 are contained within interneurons and neurons, respectively.In the brain of infected animals, the lack of change observed in arginase activity indicates that polyamine production is not enhanced. Increases in DDAH-2 isoform may contribute to the overproduction of NO. These changes are at variance with those reported in the periphery. As a whole, the above processes may ensure additive protection

  7. Prophylactic action of Alpha-tocopherol against Gamma irradiation changes in total lipid and phospholipid contents of brain cerebral hemispheres in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Mahdy, A M; Helen, N S; Roushdy, H M [National Centre for Radiation Research and Technology, Cairo (Egypt)

    1987-12-31

    Male albino rats were intraperitoneally injected with Gamma tocopherol (vitamin E) at 10 mg/100 g animal body weight, 2 hr, before irradiation exposure. exposure. Rats were then exposed to a whole body dose of gamma irradiation at 7 Gy. Rats were sacrificed 1, 3, 7 and 10 days post irradiation. The two cerebral hemispheres were taken to determine the phospholipids and total lipid contents. whole body gamma irradiation of rats at 7 Gy caused a significant decrease in the levels of both phospholipids and total lipid contents in the cerebral hemispheres on the 3 rd, 7 Th, and 10 Th days post-irradiation, the decrease was insignificant on the 1 st day post exposure. The variations were less pronounced in rats treated with vitamin E. The results obtained were discussed in view of the relevant literature. 2 tabs.

  8. Insulin promotes diacylglycerol kinase activation by different mechanisms in rat cerebral cortex synaptosomes.

    Science.gov (United States)

    Zulian, Sandra E; Ilincheta de Boschero, Mónica G; Giusto, Norma M

    2006-10-01

    The mechanism by which insulin increases diacylglycerol kinase (DAGK) activity has been studied in cerebral cortex (CC) synaptosomes from adult (3-4 months of age) rats. The purpose of this study was to identify the role of phospholipases C and D (PLC and PLD) in DAGK activation by insulin. Neomycin, an inhibitor of PLC phosphatidylinositol-bisphosphate (PIP2) specific; ethanol, an inhibitor of phosphatidic acid (PA) formation by the promotion of a transphosphatidyl reaction of phosphatidylcholine phospholipase D (PC-PLD); and DL propranolol, an inhibitor of phosphatidate phosphohydrolase (PAP), were used in this study. Insulin (0.1 microM) shielded an increase in PA synthesis by [32P] incorporation using [gamma-32P]ATP as substrate and endogenous diacylglycerol (DAG) as co-substrate. This activated synthesis was strongly inhibited either by ethanol or DL propranolol. Pulse chase experiments also showed a PIP2-PLC activation within 1 min exposure to insulin. When exogenous unsaturated 18:0-20:4 DAG was present, insulin increased PA synthesis significantly. However, this stimulatory effect was not observed in the presence of exogenous saturated (di-16:0). In the presence of R59022, a selective DAGK inhibitor, insulin exerted no stimulatory effect on [32P]PA formation, suggesting a strong relationship between increased PA formation by insulin and DAGK activity. These data indicate that the increased synthesis of PA by insulin could be mediated by the activation of both a PC-PLD pathway to provide DAG and a direct DAGK activation that is associated to the use of 18:0-20:4 DAG species. PIP2-PLC activation may contribute at least partly to the insulin effect on DAGK activity. Copyright 2006 Wiley-Liss, Inc.

  9. Central alpha2 adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve

    International Nuclear Information System (INIS)

    Adler, C.H.

    1986-01-01

    The alpha 2 adrenergic receptor subtype is thought to play a role in the mechanism of action of antidepressant and antihypertensive drugs. This thesis has attempted to shed light on the regulation of central alpha 2 adrenergic receptors in the rat cerebral cortex. Repopulation kinetics analysis allows for the determination of the rate of receptor production, rate constant of degradation, and half-life of the receptor. This analysis was carried out using both radioligand binding and functional receptor assays at various times following the irreversible inactivation of central alpha 2 adrenergic receptors by in vivo administration of N-ethoxycarbonyl-2-ethyoxy-1,2-dihydroquinoline (EEDQ). Both alpha 2 agonist and antagonist ligand binding sites recovered with a t/sub 1/2/ equal to approximately 4 days. The function of alpha 2 adrenergic autoreceptors, which inhibit stimulation-evoked release of 3 H-norepinephrine ( 3 H-NE) and alpha 2 adrenergic heteroreceptors which inhibit stimulation-evoked release of 3 H-serotonin ( 3 H-5-HT) were assayed. The t/sub 1/2/ for recovery of maximal autoreceptor and heteroreceptor function was 2.4 days and 4.6 days, respectively. The demonstration of a receptor reserve is critical to the interpretation of past and future studies of the alpha 2 adrenergic receptor since it demonstrates that: (1) alterations in the number of alpha 2 adrenergic receptor binding sites cannot be extrapolated to the actual function of the alpha 2 adrenergic receptor; and (2) alterations in the number of alpha 2 receptors is not necessarily accompanied by a change in the maximum function being studied, but may only result in shifting of the dose-response curve

  10. Phosphodiesterase inhibitors enhance object memory independent of cerebral blood flow and glucose utilization in rats.

    Science.gov (United States)

    Rutten, Kris; Van Donkelaar, Eva L; Ferrington, Linda; Blokland, Arjan; Bollen, Eva; Steinbusch, Harry Wm; Kelly, Paul At; Prickaerts, Jos Hhj

    2009-07-01

    Phosphodiesterase (PDE) inhibitors prevent the breakdown of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), and are currently studied as possible targets for cognitive enhancement. Earlier studies indicated beneficial effects of PDE inhibitors in object recognition. In this study we tested the effects of three PDE inhibitors on spatial memory as assessed in a place and object recognition task. Furthermore, as both cAMP and cGMP are known vasodilators, the effects of PDE inhibition on cognitive functions could be explained by enhancement of cerebrovascular function. We examined this possibility by measuring the effects of PDE5 and PDE4 inhibitor treatment on local cerebral blood flow and glucose utilization in rats using [14C]-iodoantipyrine and [14C]-2-deoxyglucose quantitative autoradiography, respectively. In the spatial location task, PDE5 inhibition (cGMP) with vardenafil enhanced only early phase consolidation, PDE4 inhibition (cAMP) with rolipram enhanced only late phase consolidation, and PDE2 inhibition (cAMP and cGMP) with Bay 60-7550 enhanced both consolidation processes. Furthermore, PDE5 inhibition had no cerebrovascular effects in hippocampal or rhinal areas. PDE4 inhibition increased rhinal, but not hippocampal blood flow, whereas it decreased glucose utilization in both areas. In general, PDE5 inhibition decreased the ratio between blood flow and glucose utilization, indicative of general oligaemia; whereas PDE4 inhibition increased this ratio, indicative of general hyperemia. Both oligaemic and hyperemic conditions are detrimental for brain function and do not explain memory enhancement. These results underscore the specific effects of cAMP and cGMP on memory consolidation (object and spatial memory) and provide evidence that the underlying mechanisms of PDE inhibition on cognition are independent of cerebrovascular effects.

  11. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Evidence that two stereochemically different alpha-2 adrenoceptors modulate norepinephrine release in rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Harsing, L.G. Jr.; Vizi, E.S. (Institute of Experimental Medicine, Budapest (Hungary))

    1991-01-01

    Cerebral cortex slices from the rat were loaded with (3H)norepinephrine ((3H)NE) and superfused in order to measure the release of radioactivity at rest and in response to electrical stimulation. The (-)-isomer and the (+)-isomer of CH-38083 (7,8-(methylenedioxy)-14- alpha-hydroxyalloberbane HCl), a selective alpha-2-adrenoceptor antagonist with an alloberbane skeleton, increased the electrically induced release of (3H)NE in a concentration-dependent manner, and a similar effect was observed with racemic CH-38083 and idazoxan. The stereoisomers of CH-38083 applied in a concentration range of 10(-8) to 10(-6) mol/l were equipotent in facilitating stimulation-evoked (3H)NE release: concentrations needed to enhance tritium outflow by 50% were 1.3 X 10(-7) mol/l for (-)-CH-38083 and 1.4 X 10(-7) mol/l for (+)-CH-38083. Exogenous NE decreased the electrically stimulated release of (3H)NE, and the stereoisomers of CH-38083 antagonized this inhibition with different potencies: the dissociation constant (KB) values for (-)-isomer and for (+)-isomer of CH-38083 were 14.29 and 97.18 nmol/l. These data indicate that presynaptic alpha-2 adrenoceptors that are available for NE released from axon terminals do not show stereospecificity toward enantiomers of CH-38083, whereas those that are occupied by exogenous NE are much more sensitive toward (-)-CH-38083. The alpha-1 adrenoceptor antagonist prazosin also differentiated between the alpha-2 adrenoceptor subtypes: prazosin (10(-6) mol/l) did not alter the increase of electrically induced (3H)NE release evoked by (-)- and (+)-CH-38083; however, in its presence, the stereoisomers of CH-38083 failed to antagonize the inhibitory effect of exogenous NE on its own release.

  13. Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

    International Nuclear Information System (INIS)

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2008-01-01

    ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD 50 ; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increase in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics

  14. Postoperative intermittent fasting prevents hippocampal oxidative stress and memory deficits in a rat model of chronic cerebral hypoperfusion.

    Science.gov (United States)

    Hu, Yuan; Zhang, Miao; Chen, Yunyun; Yang, Ying; Zhang, Jun-Jian

    2018-01-11

    Whether intermittent fasting (IF) treatment after stroke can prevent its long-term detrimental effects remains unknown. Here, we investigate the effects of postoperative IF on cognitive deficits and its underlying mechanisms in a permanent two-vessel occlusion (2VO) vascular dementia rat model. Rats were subjected to either IF or ad libitum feeding 1 week after 2VO surgery. The cognition of rats was assessed using the novel object recognition (NOR) task and Morris water maze (MWM) 8 weeks after surgery. After behavioral testing, hippocampal malondialdehyde (MDA) and glutathione (GSH) concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein levels, and microglia density were determined. Postoperative IF significantly ameliorated the cognitive performance of 2VO rats in the NOR and MWM tests. Cognitive enhancement paralleled preservation of the PSD95 and BDNF levels in the 2VO rat hippocampus. Mechanistically, postoperative IF mitigated hippocampal oxidative stress in 2VO rats, as indicated by the reduced MDA concentration and mRNA and the protein levels of the reactive oxygen species-generating enzyme nicotinamide adenine dinucleotide phosphate oxidase 1. IF treatment also preserved the GSH level and SOD activity, as well as the levels of their upstream regulating enzymes, resulting in preserved antioxidative capability. In addition, postoperative IF prevented hippocampal microglial activation and elevation of sphingosine 1-phosphate receptor 1 and inflammatory cytokines in 2VO rats. Our results suggest that postoperative IF suppresses neuroinflammation and oxidative stress induced by chronic cerebral ischemia, thereby preserving cognitive function in a vascular dementia rat model.

  15. [Effect of Electroacupuncture on Cerebro-cortex Caspase-3 Expression and Blood Lipid Levels in Hyperlipemia Rats with Cerebral Ischemia].

    Science.gov (United States)

    Wang, Zhuo-Yu; Ma, Jia-Jia; Guan, Han-Yu; Tian, Yao; Ren, Xiu-Jun; Ma, Hui-Fang

    2017-04-25

    To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40), "Sanyinjiao" (SP 6) plus manual acupuncture (MA) stimulation of "Shuigou" (GV 26) and "Baihui" (GV 20) on Caspase-3 protein expression in the cerebral cortex of rats with hyperlipemia and cerebral ischemia(HL-CI),so as to reveal its mechanisms underlying improvement of HL-CI. Forty-five rats were randomly divided into normal control,sham operation,model,EA group I(EA+MA was given for 14 days, i.e., 7 days before CI, and 7 days more after HL-CI)and EA group Ⅱ (EA+MA was given for only 7 days after HL-CI),with 9 rats being in each group. The HL-CI model was established by feeding the animals with high fat forage for 6 weeks and then making an occlusion of the unilateral middle cerebral artery by regional application of quantitative paper adsorbing 50% FeCl 3 solution (10 μL). Rats of the sham operation group were treated with the same procedures only without application of FeCl 3 solution. For rats of the EA group I,EA (1-3 mA, 2 Hz/100 Hz) was applied to bilateral acupoints SP 6 and ST 40 (for 20 min),and MA stimulation applied to GV 26 and GV 20. EA was conducted once daily for 7 days after 6 weeks' high fat fo-rage feeding, and EA+MA intervention was conducted once daily for 7 days after CI modeling. For rats in the EA group Ⅱ, EA+MA was applied to the same 4 acupoints once a day for 7 days only after CI modeling. The neurological impairment was assessed by Zea Longa's scoring. The blood sample was taken from the abdominal aorta for measuring the contents of serum cholesterol (CHO),triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Pathological changes of the cerebral cortex were observed after H.E. staining, and the expression of cerebro-cortex Caspase-3 was analyzed by immunohistochemistry. Following modeling,the neurological score,CHO, TG and LDL-C contents, and the number of Caspase-3 positive cells as well

  16. Subarachnoid hemorrhage induces enhanced expression of thromboxane A2 receptors in rat cerebral arteries

    DEFF Research Database (Denmark)

    Ansar, Saema; Larsen, Carl; Maddahi, Aida

    2010-01-01

    Cerebral ischemia remains the key cause of morbidity and mortality after subarachnoid hemorrhage (SAH) with a pathogenesis that is still poorly understood. The aim of the present study was to examine the involvement of thromboxane A(2) receptors (TP) in the pathophysiology of cerebral ischemia...

  17. Systemic treatment of focal brain injury in the rat by human umbilical cord blood cells being at different level of neural commitment.

    Science.gov (United States)

    Gornicka-Pawlak, El Bieta; Janowski, Miroslaw; Habich, Aleksandra; Jablonska, Anna; Drela, Katarzyna; Kozlowska, Hanna; Lukomska, Barbara; Sypecka, Joanna; Domanska-Janik, Krystyna

    2011-01-01

    The aim of the study was to evaluate therapeutic effectiveness of intra-arterial infusion of human umbilical cord blood (HUCB) derived cells at different stages of their neural conversion. Freshly isolated mononuclear cells (D-0), neurally directed progenitors (D-3) and neural-like stem cells derived from umbilical cord blood (NSC) were compared. Focal brain damage was induced in rats by stereotactic injection of ouabain into dorsolateral striatum Three days later 10(7) of different subsets of HUCB cells were infused into the right internal carotid artery. Following surgery rats were housed in enriched environment for 30 days. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam, rotarod, vibrissae elicited forelimb placing, apomorphine induced rotations), cognitive impairments (habit learning and object recognition) and exploratory behavior (open field). Thirty days after surgery the lesion volume was measured and the presence of donor cells was detected in the brain at mRNA level. At the same time immunohistochemical analysis of brain tissue was performed to estimate the local tissue response of ouabain injured rats and its modulation after HUCB cells systemic treatment. Functional effects of different subsets of cord blood cells shared substantial diversity in various behavioral tests. An additional analysis showed that D-0 HUCB cells were the most effective in functional restoration and reduction of brain lesion volume. None of transplanted cord blood derived cell fractions were detected in rat's brains at 30(th) day after treatment. This may suggest that the mechanism(s) underlying positive effects of HUCB derived cell may concern the other than direct neural cell supplementation. In addition increased immunoreactivity of markers indicating local cells proliferation and migration suggests stimulation of endogenous reparative processes by HUCB D-0 cell interarterial infusion.

  18. Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Mei-Xue Dong

    Full Text Available Recombinant tissue plasminogen activator (rtPA is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA on cerebral infarction besides its thrombolysis property in mechanical animal stroke.Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias.We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate.This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA.

  19. Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-infammatory mechanism

    Directory of Open Access Journals (Sweden)

    Yao-xian Xiang

    2015-01-01

    Full Text Available Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimulation (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-and interleukin- 6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor- and interleukin-6 expression.

  20. Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat

    DEFF Research Database (Denmark)

    Linde, Rasmus; Hasselbalch, Steen G.; Topp, Simon

    2006-01-01

    and cerebral metabolism could not be explained by alterations in blood pH or arterial CO2 tension. By measuring cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy, it could further be concluded that the brain pH was unchanged during acute hyperketonemia. These observations indicate......In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated...... that the mechanism responsible for the increase in CBF is rather a direct effect on the cerebral endothelium than via some metabolic interactions...

  1. Reduction of superoxide dismutase activity correlates with visualization of edema by T[sub 2]-weighted MR imaging in focal ischemic rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Imaizumi, Shigeki; Chang, LeeHong; Cohen, Yoram; Chan, P H; Weinstein, P R; James, T L [California Univ., San Francisco, CA (United States); Yoshimoto, Takashi

    1994-01-01

    This study investigated the correlation between in vivo serial T[sub 2]-weighted magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na[sup +]), and potassium ion (K[sup +]) contents measured in vitro using rat brain following right middle cerebral artery occlusion in conjunction with bilateral common carotid artery (CCA) occlusion. One hour later the left CCA was released. Serial MR images showed edema developed from the outer cortex towards the center. The T[sub 2] signal intensity of the injured right cortex increased with time compared to that of the contralateral cortex. Increased Na[sup +] and water and decreased K[sup +] contents occurred in the injured cortex, indicating that serial T[sub 2]-weighted MR imaging reflects the changes in water content and Na[sup +] and K[sup +] concentrations determined by biochemical techniques. GSH-Px activity was little changed. Total SOD in the injured cortex decreased 1 hour after ischemia and remained low throughout the experiment. In contrast, SOD activity in the noninfarcted left cortex also decreased after 1 hour but returned to normal after 2 hours of ischemia. Our results suggest that oxygen free radicals are important in developing ischemic brain edema and cerebral infarction. (author).

  2. Reduction of superoxide dismutase activity correlates with visualization of edema by T2-weighted MR imaging in focal ischemic rat brain

    International Nuclear Information System (INIS)

    Imaizumi, Shigeki; Chang, LeeHong; Cohen, Yoram; Chan, P.H.; Weinstein, P.R.; James, T.L.; Yoshimoto, Takashi.

    1994-01-01

    This study investigated the correlation between in vivo serial T 2 -weighted magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na + ), and potassium ion (K + ) contents measured in vitro using rat brain following right middle cerebral artery occlusion in conjunction with bilateral common carotid artery (CCA) occlusion. One hour later the left CCA was released. Serial MR images showed edema developed from the outer cortex towards the center. The T 2 signal intensity of the injured right cortex increased with time compared to that of the contralateral cortex. Increased Na + and water and decreased K + contents occurred in the injured cortex, indicating that serial T 2 -weighted MR imaging reflects the changes in water content and Na + and K + concentrations determined by biochemical techniques. GSH-Px activity was little changed. Total SOD in the injured cortex decreased 1 hour after ischemia and remained low throughout the experiment. In contrast, SOD activity in the noninfarcted left cortex also decreased after 1 hour but returned to normal after 2 hours of ischemia. Our results suggest that oxygen free radicals are important in developing ischemic brain edema and cerebral infarction. (author)

  3. Repetitive Neonatal Erythropoietin and Melatonin Combinatorial Treatment Provides Sustained Repair of Functional Deficits in a Rat Model of Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Lauren L. Jantzie

    2018-04-01

    Full Text Available Cerebral palsy (CP is the leading cause of motor impairment for children worldwide and results from perinatal brain injury (PBI. To test novel therapeutics to mitigate deficits from PBI, we developed a rat model of extreme preterm birth (<28 weeks of gestation that mimics dual intrauterine injury from placental underperfusion and chorioamnionitis. We hypothesized that a sustained postnatal treatment regimen that combines the endogenous neuroreparative agents erythropoietin (EPO and melatonin (MLT would mitigate molecular, sensorimotor, and cognitive abnormalities in adults rats following prenatal injury. On embryonic day 18 (E18, a laparotomy was performed in pregnant Sprague–Dawley rats. Uterine artery occlusion was performed for 60 min to induce placental insufficiency via transient systemic hypoxia-ischemia, followed by intra-amniotic injections of lipopolysaccharide, and laparotomy closure. On postnatal day 1 (P1, approximately equivalent to 30 weeks of gestation, injured rats were randomized to an extended EPO + MLT treatment regimen, or vehicle (sterile saline from P1 to P10. Behavioral assays were performed along an extended developmental time course (n = 6–29. Open field testing shows injured rats exhibit hypermobility and disinhibition and that combined neonatal EPO + MLT treatment repairs disinhibition in injured rats, while EPO alone does not. Furthermore, EPO + MLT normalizes hindlimb deficits, including reduced paw area and paw pressure at peak stance, and elevated percent shared stance after prenatal injury. Injured rats had fewer social interactions than shams, and EPO + MLT normalized social drive. Touchscreen operant chamber testing of visual discrimination and reversal shows that EPO + MLT at least partially normalizes theses complex cognitive tasks. Together, these data indicate EPO + MLT can potentially repair multiple sensorimotor, cognitive, and behavioral realms following PBI, using

  4. [Effects of Naomaitong combined with mobilization of bone marrow mesenchymal stem cells on neuron apoptosis and expressions of Fas, FasL and caspase-3 proteins in rats with cerebral ischemia].

    Science.gov (United States)

    Li, Jian-sheng; Liu, Jing-xia; Tian, Yu-shou; Ren, Wei-hong; Zhang, Xin-feng; Wang, Ding-chao

    2009-09-01

    To observe the effects of Naomaitong, a compound traditional Chinese herbal medicine, combined with mobilization of bone marrow mesenchymal stem cells (BMSCs) on neuron apoptosis in rats with cerebral ischemia, and to explore the possible mechanism by detecting the expressions of Fas, FasL and caspase-3 proteins. Two hundred and two SD rats were divided into sham-operated group, untreated group, recombinant granulocyte colony-stimulating factor (rG-CSF) group, Naomaitong group and Naomaitong plus rG-CSF group (combination group). Focal cerebral ischemia was induced by intraluminal middle cerebral artery occlusion using a nylon thread with some modification. Rats in the rG-CSF group and the untreated group were administered with rG-CSF 10 microg/(kg x d) by subcutaneous injection 3 d before and 2 d after the operation respectively, once a day, and rats in the Naomaitong group and the combination group were intragastrically administered Naomaitong before and after the operation until sacrificed. Two, three, seven and fourteen days after operation, count of CD34-positive cells in peripheral blood and CD34 expression in brain tissue were determined. General neural function score (GNFS) was evaluated. Neuron apoptosis, expressions of Fas, FasL and caspase-3 in rat's brain were all measured. Count of CD34-positive cells in peripheral blood and CD34 expression in brain tissue were high in the untreated group, and reached the peak at 3 d and 7 d respectively. CD34 expression in brain tissue was increased in each treated group, especially in the combination group. GNFS was increased at 3 d and 7 d in the untreated group, 7 d and 14 d in the rG-CSF group and the combination group. Expressions of Fas, FasL and caspase-3 were increased 2, 3 and 7 d after operation, while expression of FasL at 2 d in the rG-CSF group, expressions of Fas, FasL and caspase-3 in the combination group were decreased. Expressions of Fas, FasL and caspase-3 at 7 d and 14 d in the combination group

  5. Surgical pathology of epilepsy-associated non-neoplastic cerebral lesions: a brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia

    Science.gov (United States)

    Miyata, Hajime; Hori, Tomokatsu; Vinters, Harry V.

    2014-01-01

    Among epilepsy-associated non-neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and malformation of cortical development (MCD) including focal cortical dysplasia (FCD), are the two most frequent causes of drug-resistant focal epilepsies constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlation; results, however, have been controversial, particularly in terms of postsurgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological study. Meanwhile, we reviewed neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and severity of neuronal loss and gliosis within hippocampal formation; i.e., HS type 1 (61%) equivalent to ‘classical’ Ammon’s horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore we performed a neuropathological comparative study on mTLE-HS and dementia associated HS (d-HS) in elderly, and confirmed that neuropathological features differ between mTLE-HS and d-HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes particularly Alzheimer type and TDP-43 pathologies. These

  6. Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism.

    Science.gov (United States)

    Gispert, Juan D; Figueiras, Francisca P; Vengeliene, Valentina; Herance, José R; Rojas, Santiago; Spanagel, Rainer

    2017-06-01

    Several [ 18 F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [ 18 F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [ 18 F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [ 18 F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Dl-3-n-Butylphthalide Treatment Enhances Hemodynamics and Ameliorates Memory Deficits in Rats with Chronic Cerebral Hypoperfusion

    Directory of Open Access Journals (Sweden)

    Zhilin Xiong

    2017-07-01

    Full Text Available Our previous study has revealed that chronic cerebral hypoperfusion (CCH activates a compensatory vascular mechanism attempting to maintain an optimal cerebral blood flow (CBF. However, this compensation fails to prevent neuronal death and cognitive impairment because neurons die prior to the restoration of normal CBF. Therefore, pharmacological invention may be critical to enhance the CBF for reducing neurodegeneration and memory deficit. Dl-3-n-butylphthalide (NBP is a compound isolated from the seeds of Chinese celery and has been proven to be able to prevent neuronal loss, reduce inflammation and ameliorate memory deficits in acute ischemic animal models and stroke patients. In the present study, we used magnetic resonance imaging (MRI techniques, immunohistochemistry and Morris water maze (MWM to investigate whether NBP can accelerate CBF recovery, reduce neuronal death and improve cognitive deficits in CCH rats after permanent bilateral common carotid artery occlusion (BCCAO. Rats were intravenously injected with NBP (5 mg/kg daily for 14 days beginning the first day after BCCAO. The results showed that NBP shortened recovery time of CBF to pre-occlusion levels at 2 weeks following BCCAO, compared to 4 weeks in the vehicle group, and enhanced hemodynamic compensation through dilation of the vertebral arteries (VAs and increase in angiogenesis. NBP treatment also markedly reduced reactive astrogliosis and cell apoptosis and protected hippocampal neurons against ischemic injury. The escape latency of CCH rats in the MWM was also reduced in response to NBP treatment. These findings demonstrate that NBP can accelerate the recovery of CBF and improve cognitive function in a rat model of CCH, suggesting that NBP is a promising therapy for CCH patients or vascular dementia.

  8. La atorvastatina protege las neuronas gabérgicas y dopaminérgicas del sistema nigroestriatal en un modelo experimental de isquemia cerebral focal transitoria en ratas

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    Angélica María Sabogal

    2014-06-01

    Full Text Available Introducción. La isquemia cerebral es la tercera causa de muerte y la primera de discapacidad permanente en el mundo. La atorvastatina es un fármaco neuroprotector prometedor para el tratamiento de la apoplejía; sin embargo, su acción sobre las poblaciones neuronales del sistema nigroestriatal después de la isquemia aún se desconoce. Objetivo. Evaluar el efecto de la atorvastatina sobre poblaciones gabérgicas y dopaminérgicas en regiones exofocales en un modelo de oclusión transitoria de la arteria cerebral media. Materiales y métodos. Se utilizaron 28 ratas Wistar macho de ocho semanas de edad. Los ejemplares con isquemia simulada y los ejemplares sometidos a isquemia fueron tratados con atorvastatina (10 mg/kg y carboximetilcelulosa (placebo administrados por medio de sonda a las 6, 24, 48 y 72 horas después de la reperfusión. Se analizó la inmunorreacción de la descarboxilasa del ácido glutámico y de la tirosina hidroxilasa en el globo pálido, el putamen caudado y la sustancia negra. Resultados. Los datos confirmaron el daño neurológico y la pérdida celular en el putamen caudado. Se incrementó la inmunorreacción de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata, disminuyendo la inmunorreacción de la descarboxilasa del ácido glutámico en el globo pálido lateral de los animales isquémicos tratados con placebo; sin embargo, el tratamiento con atorvastatina pudo revertirla, lo que logró una disminución significativa de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata y aumentando los niveles de descarboxilasa del ácido glutámico en el globo pálido lateral. Conclusión. Nuestros datos sugieren que la atorvastatina en el tratamiento posterior a la isquemia ejerce neuroprotección en las zonas exofocales, modulando las poblaciones neuronales gabérgicas y dopaminérgicas del sistema nigroestriatal, lo que podría prevenir trastornos neurológicos.

  9. Morphological changes of cerebral vessels and expression patterns of MMP-2 and MMP-9 on cerebrovascular wall of alcoholic rats.

    Science.gov (United States)

    Qi, Qian; Liu, Xia; Zhang, Guozhong; He, Wenjing; Ma, Rufei; Cong, Bin; Li, Yingmin

    2014-01-01

    Alcohol abuse increases the incidence of cerebral accidents, which correlates with cerebrovascular structural changes. The present study was designed to observe the cerebrovascular remodeling of drinking rats with light microscopy and transmission electron microscopy (TEM). Short-term alcohol administration induced apparent amplification of perivascular spaces around small vessels in brain tissue, while long-term administration caused pathological changes of basilar arteries (BAs), including endothelial exfoliation, inner elastic lamina (IEL) fragmentation and thickening of tunica media and adventitia. In addition, the relationship between cerebrovascular remodeling and MMP-2 and MMP-9 synthesized by endothelial cells and vascular smooth muscle cells was explored by immunohistochemistry. The two protein expression in cerebral vessels changed dynamically, peaking at 1-2 weeks after treatment, and decreasing as treatment continued. These results suggest that MMP-2 and MMP-9 may play a significant role in blood-brain barrier disruption after alcohol abuse. But the chronic changes of cerebral arteries resulted from drinking are not coincident with time course of MMP-2 and MMP-9 expression in situ.

  10. Detection of TRPV4 channel current-like activity in Fawn Hooded hypertensive (FHH rat cerebral arterial muscle cells.

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    Debebe Gebremedhin

    Full Text Available The transient receptor potential vallinoid type 4 (TRPV4 is a calcium entry channel known to modulate vascular function by mediating endothelium-dependent vasodilation. The present study investigated if isolated cerebral arterial myocytes of the Fawn Hooded hypertensive (FHH rat, known to display exaggerated KCa channel current activity and impaired myogenic tone, express TRPV4 channels at the transcript and protein level and exhibit TRPV4-like single-channel cationic current activity. Reverse transcription polymerase chain reaction (RT-PCR, Western blot, and immunostaining analysis detected the expression of mRNA transcript and translated protein of TRPV4 channel in FHH rat cerebral arterial myocytes. Patch clamp recording of single-channel current activity identified the presence of a single-channel cationic current with unitary conductance of ~85 pS and ~96 pS at hyperpolarizing and depolarizing potentials, respectively, that was inhibited by the TRPV4 channel antagonist RN 1734 or HC 067074 and activated by the potent TRPV4 channel agonist GSK1016790A. Application of negative pressure via the interior of the patch pipette increased the NPo of the TRPV4-like single-channel cationic current recorded in cell-attached patches at a patch potential of 60 mV that was inhibited by prior application of the TRPV4 channel antagonist RN 1734 or HC 067047. Treatment with the TRPV4 channel agonist GSK1016790A caused concentration-dependent increase in the NPo of KCa single-channel current recorded in cell-attached patches of cerebral arterial myocytes at a patch potential of 40 mV, which was not influenced by pretreatment with the voltage-gated L-type Ca2+ channel blocker nifedipine or the T-type Ca2+ channel blocker Ni2+. These findings demonstrate that FHH rat cerebral arterial myocytes express mRNA transcript and translated protein for TRPV4 channel and display TRPV4-like single-channel cationic current activity that was stretch-sensitive and

  11. New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration.

    Science.gov (United States)

    Berthet, Carole; Castillo, Ximena; Magistretti, Pierre J; Hirt, Lorenz

    2012-01-01

    Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and histological benefits persisting 2 weeks after ischaemia. Importantly, lactate also protects after systemic intravenous administration, a more suitable route of administration in a clinical emergency setting. These findings provide further steps to bring this physiological, commonly available and inexpensive neuroprotectant closer to clinical translation for stroke. Copyright © 2012 S. Karger AG, Basel.

  12. Preconditioning with the traditional Chinese medicine Huang-Lian-Jie-Du-Tang initiates HIF-1α-dependent neuroprotection against cerebral ischemia in rats.

    Science.gov (United States)

    Zhang, Qichun; Bian, Huimin; Li, Yu; Guo, Liwei; Tang, Yuping; Zhu, Huaxu

    2014-06-11

    Huang-Lian-Jie-Du-Tang (HLJDT) is a classical heat-clearing and detoxicating formula of traditional Chinese medicine that is widely used to treat stroke. The present study was designed to investigate the effects of HLJDT preconditioning on neurons under oxygen and glucose deprivation (OGD) and rats subjected to middle cerebral artery occlusion (MCAO). A stroke model of rats was obtained through MCAO. Following HLJDT preconditioning, the cerebral infarction volume, cerebral water content, and neurological deficient score were determined. Cerebral cortical neurons cultured in vitro were preconditioned with HLJDT and then subjected to OGD treatment. The release of lactate dehydrogenase (LDH) from neurons was detected. The levels of hypoxia-inducible factor-1α (HIF-1α) and PI3K/Akt signaling were analyzed by western blotting, and the levels of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in the supernatant of the neurons and the plasma of MCAO rats were measured through a radioimmunological assay. The apoptosis and proliferation of neurons were analyzed by immunohistochemistry. HLJDT preconditioning significantly reduced the cerebral infarction volume and cerebral water content and ameliorated the neurological deficient score of MCAO rats. In addition, HLJDT preconditioning protected neurons against OGD. Increased HIF-1α, EPO, and VEGF levels and the activation of PI3K/Akt signaling were observed as a result of HLJDT preconditioning. Furthermore, HLJDT preconditioning was found to inhibit ischemia-induced neuron apoptosis and to promote neuron proliferation under conditions of ischemia/reperfusion. Both rats and neurons subjected to HLJDT preconditioning were able to resist ischemia/reperfusion or hypoxia injury through the inhibition of apoptosis and the enhancement of proliferation, and these effects were primarily dependent on the activation of the PI3K/Akt signaling pathway and HIF-1α. Copyright © 2014 Elsevier Ireland Ltd. All rights

  13. Curcumin modulates dopaminergic receptor, CREB and phospholipase c gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats

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    George Naijil

    2010-05-01

    Full Text Available Abstract Curcumin, an active principle component in rhizome of Curcuma longa, has proved its merit for diabetes through its anti-oxidative and anti-inflammatory properties. This study aims at evaluating the effect of curcumin in modulating the altered dopaminergic receptors, CREB and phospholipase C in the cerebral cortex and cerebellum of STZ induced diabetic rats. Radioreceptor binding assays and gene expression was done in the cerebral cortex and cerebellum of male Wistar rats using specific ligands and probes. Total dopaminergic receptor binding parameter, Bmax showed an increase in cerebral cortex and decrease in the cerebellum of diabetic rats. Gene expression studies using real time PCR showed an increased expression of dopamine D1 and D2 receptor in the cerebral cortex of diabetic rats. In cerebellum dopamine D1 receptor was down regulated and D2 receptor showed an up regulation. Transcription factor CREB and phospholipase C showed a significant down regulation in cerebral cortex and cerebellum of diabetic rats. We report that curcumin supplementation reduces diabetes induced alteration of dopamine D1, D2 receptors, transcription factor CREB and phospholipase C to near control. Our results indicate that curcumin has a potential to regulate diabetes induced malfunctions of dopaminergic signalling, CREB and Phospholipase C expression in cerebral cortex and cerebellum and thereby improving the cognitive and emotional functions associated with these regions. Furthermore, in line with these studies an interaction between curcumin and dopaminergic receptors, CREB and phospholipase C is suggested, which attenuates the cortical and cerebellar dysfunction in diabetes. These results suggest that curcumin holds promise as an agent to prevent or treat CNS complications in diabetes.

  14. Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats.

    Science.gov (United States)

    Kumar, T Peeyush; Antony, Sherin; Gireesh, G; George, Naijil; Paulose, C S

    2010-05-31

    Curcumin, an active principle component in rhizome of Curcuma longa, has proved its merit for diabetes through its anti-oxidative and anti-inflammatory properties. This study aims at evaluating the effect of curcumin in modulating the altered dopaminergic receptors, CREB and phospholipase C in the cerebral cortex and cerebellum of STZ induced diabetic rats. Radioreceptor binding assays and gene expression was done in the cerebral cortex and cerebellum of male Wistar rats using specific ligands and probes. Total dopaminergic receptor binding parameter, B(max) showed an increase in cerebral cortex and decrease in the cerebellum of diabetic rats. Gene expression studies using real time PCR showed an increased expression of dopamine D1 and D2 receptor in the cerebral cortex of diabetic rats. In cerebellum dopamine D1 receptor was down regulated and D2 receptor showed an up regulation. Transcription factor CREB and phospholipase C showed a significant down regulation in cerebral cortex and cerebellum of diabetic rats. We report that curcumin supplementation reduces diabetes induced alteration of dopamine D1, D2 receptors, transcription factor CREB and phospholipase C to near control. Our results indicate that curcumin has a potential to regulate diabetes induced malfunctions of dopaminergic signalling, CREB and Phospholipase C expression in cerebral cortex and cerebellum and thereby improving the cognitive and emotional functions associated with these regions. Furthermore, in line with these studies an interaction between curcumin and dopaminergic receptors, CREB and phospholipase C is suggested, which attenuates the cortical and cerebellar dysfunction in diabetes. These results suggest that curcumin holds promise as an agent to prevent or treat CNS complications in diabetes.

  15. Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Jielu Tan; Xiangrong Zheng; Shanshan Zhang; Yujia Yang; Xia Wang; Xiaohe Yu; Le Zhong

    2014-01-01

    Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into ifve groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular en-dothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. hTe cerebral palsy model was established by ligating the letf common carotid artery followed by exposure to hypox-ia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. Atfer transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vas-cular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for ifnding water and the ifnding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. hTese ifndings indicate that the transplantation of vascu-lar endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deifcits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

  16. MR-angiography allows defining severity grades of cerebral vasospasm in an experimental double blood injection subarachnoid hemorrhage model in rats.

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    Vesna Malinova

    Full Text Available Magnetic resonance (MR imaging has been used for the detection of cerebral vasospasm (VSP related infarction in experimental subarachnoid hemorrhage (eSAH in rats. Conventional angiography is generally used to visualize VSP, which is an invasive technique with a possible increase in morbidity and mortality. In this study we evaluated the validity of MR-angiography (MRA in detecting VSP and its feasibility to define VSP severity grades after eSAH in rats.SAH was induced using the double-hemorrhage model in 12 rats. In two rats, saline solution was injected instead of blood (sham group. MR was performed on day 1, 2 and on day 5. T1-, T2-, T2*-weighted and time-of-flight MR sequences were applied, which were analyzed by two blinded neuroradiologists. Vessel narrowing of 25-50% was defined as mild, 50-75% as moderate and >75% as severe VSP.We performed a total of 34 MRAs in 14 rats. In 14 rats, MRA was performed on day 2 and day 5. In six rats MRA was additionally performed on day1 before the blood injection. A good visualization of cerebral vessels was possible in all cases. No VSP was seen in the sham group neither on day 2 nor on day 5. We found vasospasm on day 2 in 7 of the 14 rats (50% whereas all 7 rats had mild and one rat had additionally moderate and severe vasospasm in one vessel, respectively. On day 5 we found vasospasm in 8 of the 14 rats (60% whereas 4 rats had severe vasospasm, 1 rat had moderate vasospasm and 3 rats demonstrated mild vasospasm. In 4 of the 14 rats (30% an ischemic lesion was detected on day 5. Three of these rats had severe vasospasm and one rat had mild vasospasm. Severe vasospasm on day 5 was statistically significant correlated with the occurrence of ischemic lesions (Fisher's Exact test, OR 19.5, p = 0.03.MRA is a noninvasive diagnostic tool, which allows a good visualization of the cerebral vasculature and provides reproducible results concerning the detection of VSP and the differentiation into three severity

  17. The effect of isovolemic hemodilution with oxycyte, a perfluorocarbon emulsion, on cerebral blood flow in rats.

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    Zhong-jin Yang

    Full Text Available BACKGROUND: Cerebral blood flow (CBF is auto-regulated to meet the brain's metabolic requirements. Oxycyte is a perfluorocarbon emulsion that acts as a highly effective oxygen carrier compared to blood. The aim of this study is to determine the effects of Oxycyte on regional CBF (rCBF, by evaluating the effects of stepwise isovolemic hemodilution with Oxycyte on CBF. METHODOLOGY: Male rats were intubated and ventilated with 100% O(2 under isoflurane anesthesia. The regional (striatum CBF (rCBF was measured with a laser doppler flowmeter (LDF. Stepwise isovolemic hemodilution was performed by withdrawing 4ml of blood and substituting the same volume of 5% albumin or 2 ml Oxycyte plus 2 ml albumin at 20-minute intervals until the hematocrit (Hct values reached 5%. PRINCIPAL FINDINGS: In the albumin-treated group, rCBF progressively increased to approximately twice its baseline level (208+/-30% when Hct levels were less than 10%. In the Oxycyte-treated group on the other hand, rCBF increased by significantly smaller increments, and this group's mean rCBF was only slightly higher than baseline (118+/-18% when Hct levels were less than 10%. Similarly, in the albumin-treated group, rCBF started to increase when hemodilution with albumin caused the CaO(2 to decrease below 17.5 ml/dl. Thereafter, the increase in rCBF was accompanied by a nearly proportional decrease in the CaO(2 level. In the Oxycyte-treated group, the increase in rCBF was significantly smaller than in the albumin-treated group when the CaO(2 level dropped below 10 ml/dl (142+/-20% vs. 186+/-26%, and rCBF returned to almost baseline levels (106+/-15 when the CaO(2 level was below 7 ml/dl. CONCLUSIONS/SIGNIFICANCE: Hemodilution with Oxycyte was accompanied with higher CaO(2 and PO(2 than control group treated with albumin alone. This effect may be partially responsible for maintaining relatively constant CBF and not allowing the elevated blood flow that was observed with albumin.

  18. Therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Guo, Chao; Zhu, Yanrong; Weng, Yan; Wang, Shiquan; Guan, Yue; Wei, Guo; Yin, Ying; Xi, Miaomaio; Wen, Aidong

    2014-01-01

    Breviscapine injection is a Chinese herbal medicine standardized product extracted from Erigeron breviscapus (Vant.) Hand.-Mazz. It has been widely used for treating cardiovascular and cerebrovascular diseases. However, the therapeutic time window and the action mechanism of breviscapine are still unclear. The present study was designed to investigate the therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemic/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2h followed by 24h of reperfusion. Experiment part 1 was used to investigate the therapeutic time window of breviscapine. Rats were injected intravenously with 50mg/kg breviscapine at different time-points of reperfusion. After 24h of reperfusion, neurologic score, infarct volume, brain water content and serum level of neuron specific enolase (NSE) were measured in a masked fashion. Part 2 was used to explore the therapeutic mechanism of breviscapine. 4-Hydroxy-2-nonenal (4-HNE), 8-hydroxyl-2'- deoxyguanosine (8-OHdG) and the antioxidant capacity of ischemia cortex were measured by ELISA and ferric-reducing antioxidant power (FRAP) assay, respectively. Immunofluorescence and western blot analysis were used to analyze the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Part 1: breviscapine injection significantly ameliorated neurologic deficit, reduced infarct volume and water content, and suppressed the levels of NSE in a time-dependent manner. Part 2: breviscapine inhibited the increased levels of 4-HNE and 8-OHdG, and enhanced the antioxidant capacity of cortex tissue. Moreover, breviscapine obviously raised the expression of Nrf2 and HO-1 proteins after 24h of reperfusion. The therapeutic time window of breviscapine injection for cerebral ischemia/reperfusion injury seemed to be within 5h after reperfusion. By up-regulating the expression of Nrf2/HO-1 pathway

  19. Evaluation of pharmacological efficacy of anti-edema agents in a rat cerebral infarction model by MRI image analysis

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Yoshio; Haida, Munetaka; Kurita, Daisaku; Shinohara, Yukito [Tokai Univ., Isehara, Kanagawa (Japan). School of Medicine; Sugiura, Takeo

    1997-04-01

    We investigated the efficacy of drugs used to treat brain edema in a rat acute cerebral infarction model by MRI image analysis. Twenty-six Sprague-Dawley rats were anesthetized with halothane, and the right middle cerebral artery was permanently occluded via a transvascular approach using a nylon 2-0 suture. At 24 hours after the occlusion, axial T{sub 2}-weighted MRI images were taken before and 2 hours after intraperitoneal administration of a test drug. After the administration of 1.7 g/kg glycerol (n=9), 3.3 g/kg mannitol (n=9) or 17 mg/kg furosemide (n=8), the high intensity area (HIA) in the whole brain amounted to 92% (p<0.01), 94% (p=0.07), or 95% (p=0.03), respectively as compared to the corresponding HIA before administration. The HIA in the cerebral cortex amounted to 87% (p<0.01), 89% (p=0.03), or 98% (p=0.47), and that in the striatum to 102%, 106%, or 87% (p<0.05), respectively. The signal intensity change (before{yields}after) was 54{yields}49 (p<0.01), 54{yields}50 (p<0.01), or 55{yields}54 in the left side normal cortex; 102{yields}97 (p<0.0l), 100{yields}98, or 98{yields}97 in the injured side cortex; and 100{yields}93 (p<0.0l), 94{yields}88 (p=0.03), or 94{yields}94 in the injured side striatum, respectively. Improvement of edema by the drugs was observed as a reduction in HIA and a decrease in signal intensity on MRI, and the changes were significant in the case of administration of each of glycerol, mannitol and furosemide. (author)

  20. Evaluation of pharmacological efficacy of anti-edema agents in a rat cerebral infarction model by MRI image analysis

    International Nuclear Information System (INIS)

    Izumi, Yoshio; Haida, Munetaka; Kurita, Daisaku; Shinohara, Yukito; Sugiura, Takeo.

    1997-01-01

    We investigated the efficacy of drugs used to treat brain edema in a rat acute cerebral infarction model by MRI image analysis. Twenty-six Sprague-Dawley rats were anesthetized with halothane, and the right middle cerebral artery was permanently occluded via a transvascular approach using a nylon 2-0 suture. At 24 hours after the occlusion, axial T 2 -weighted MRI images were taken before and 2 hours after intraperitoneal administration of a test drug. After the administration of 1.7 g/kg glycerol (n=9), 3.3 g/kg mannitol (n=9) or 17 mg/kg furosemide (n=8), the high intensity area (HIA) in the whole brain amounted to 92% (p<0.01), 94% (p=0.07), or 95% (p=0.03), respectively as compared to the corresponding HIA before administration. The HIA in the cerebral cortex amounted to 87% (p<0.01), 89% (p=0.03), or 98% (p=0.47), and that in the striatum to 102%, 106%, or 87% (p<0.05), respectively. The signal intensity change (before→after) was 54→49 (p<0.01), 54→50 (p<0.01), or 55→54 in the left side normal cortex; 102→97 (p<0.0l), 100→98, or 98→97 in the injured side cortex; and 100→93 (p<0.0l), 94→88 (p=0.03), or 94→94 in the injured side striatum, respectively. Improvement of edema by the drugs was observed as a reduction in HIA and a decrease in signal intensity on MRI, and the changes were significant in the case of administration of each of glycerol, mannitol and furosemide. (author)

  1. Extended magnetic resonance imaging studies on the effect of classically activated microglia transplantation on white matter regeneration following spinal cord focal injury in adult rats.

    Science.gov (United States)

    Marcol, Wiesław; Ślusarczyk, Wojciech; Larysz-Brysz, Magdalena; Łabuzek, Krzysztof; Kapustka, Bartosz; Staszkiewicz, Rafał; Rosicka, Paulina; Kalita, Katarzyna; Węglarz, Władysław; Lewin-Kowalik, Joanna

    2017-11-01

    Spinal cord injuries are still a serious problem for regenerative medicine. Previous research has demonstrated that activated microglia accumulate in spinal lesions, influencing the injured tissues in various ways. Therefore, transplantation of activated microglia may have a beneficial role in the regeneration of the nervous system. The present study examined the influence of transplanted activated microglial cells in adult rats with injured spinal cords. Rats were randomly divided into an experimental (M) and control (C) group, and were subjected to non-laminectomy focal injury of spinal cord white matter by means of a high-pressured air stream. In group M, activated cultured microglial cells were injected twice into the site of injury. Functional outcome and morphological features of regeneration were analyzed during a 12-week follow-up. The lesions were characterized by means of magnetic resonance imaging (MRI). Neurons in the brain stem and motor cortex were labeled with FluoroGold (FG). A total of 12 weeks after surgery, spinal cords and brains were collected and subjected to histopathological and immunohistochemical examinations. Lesion sizes in the spinal cord were measured and the number of FG-positive neurons was counted. Rats in group M demonstrated significant improvement of locomotor performance when compared with group C (Pspinal cord in the group M following microglia treatment, as compared with group C. The water diffusion perpendicular to the spinal cord in group M was closer to the reference values for a healthy spinal cord than it was in group C. The sizes of lesions were also significantly smaller in group M than in the group C (Pspinal cord gives some positive effects for the regeneration of the white matter.

  2. Extended magnetic resonance imaging studies on the effect of classically activated microglia transplantation on white matter regeneration following spinal cord focal injury in adult rats

    Science.gov (United States)

    Marcol, Wiesław; Ślusarczyk, Wojciech; Larysz-Brysz, Magdalena; Łabuzek, Krzysztof; Kapustka, Bartosz; Staszkiewicz, Rafał; Rosicka, Paulina; Kalita, Katarzyna; Węglarz, Władysław; Lewin-Kowalik, Joanna

    2017-01-01

    Spinal cord injuries are still a serious problem for regenerative medicine. Previous research has demonstrated that activated microglia accumulate in spinal lesions, influencing the injured tissues in various ways. Therefore, transplantation of activated microglia may have a beneficial role in the regeneration of the nervous system. The present study examined the influence of transplanted activated microglial cells in adult rats with injured spinal cords. Rats were randomly divided into an experimental (M) and control (C) group, and were subjected to non-laminectomy focal injury of spinal cord white matter by means of a high-pressured air stream. In group M, activated cultured microglial cells were injected twice into the site of injury. Functional outcome and morphological features of regeneration were analyzed during a 12-week follow-up. The lesions were characterized by means of magnetic resonance imaging (MRI). Neurons in the brain stem and motor cortex were labeled with FluoroGold (FG). A total of 12 weeks after surgery, spinal cords and brains were collected and subjected to histopathological and immunohistochemical examinations. Lesion sizes in the spinal cord were measured and the number of FG-positive neurons was counted. Rats in group M demonstrated significant improvement of locomotor performance when compared with group C (PMRI analysis demonstrated moderate improvement in water diffusion along the spinal cord in the group M following microglia treatment, as compared with group C. The water diffusion perpendicular to the spinal cord in group M was closer to the reference values for a healthy spinal cord than it was in group C. The sizes of lesions were also significantly smaller in group M than in the group C (P<0.05). The number of brain stem and motor cortex FG-positive neurons in group M was significantly higher than in group C. The present study demonstrated that delivery of activated microglia directly into the injured spinal cord gives some

  3. 3H-spiroperidol labels serotonin receptors in rat cerebral cortex and hippocampus

    International Nuclear Information System (INIS)

    Creese, I.; Snyder, S.H.

    1978-01-01

    It is found that in the cerebral cortex, butaclamol displaceable 3 H-spiroperidol binding labels both dopamine and serotonin receptors. In the hippocampus it is probable that 3 H-spiroperidol binding involves serotonin receptors exclusively. (Auth.)

  4. Nepeta Dschuparensis Bornm Extract Moderates COX-2 and IL-1β Proteins in a Rat Model of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Alireza Mousavi Nia

    2017-03-01

    Full Text Available Background: Nepeta dschuparensis Bornm (NP is used as a medicinal herb in Iran. In traditional medicine, this herb is extensively employed for curing ailments such as cardiovascular diseases. NP has antioxidant and anti-inflammatory properties. This project examined the effects of the NP extract on cyclooxygenase-2 (COX-2 and interleukin-1β (IL-1β protein levels and its efficacy in neuroprotection in a cerebral ischemia-reperfusion model. Methods: Twenty-six male rats were randomly divided into 3 groups: 1 sham (n=6: no middle cerebral artery occlusion (MCAO procedure, 2 control (n=10: MCAO procedure and treatment with normal saline, and 3 NP extract (n=10: MCAO procedure and treatment with the NP extract (20 mg/kg, i.p. at the beginning of reperfusion. To examine the injury caused by cerebral ischemia, we measured motor coordination and the infarct area using the rotarod test and triphenyl tetrazolium chloride staining, respectively. IL-1β and COX-2 protein levels, as inflammatory markers, were measured by immunoblotting assay. The statistical analyses were performed using SPSS, version 16, and the data are expressed as means±SEMs. Statistical difference was evaluated using the one-way ANOVA, followed by the post hoc LSD test (P<0.01. Results: Treatment with the NP extract significantly diminished the infarct volume and alleviated the motor coordination disorder induced by cerebral ischemia. The NP extract administration significantly attenuated the increase in IL-1β and COX-2 protein levels too (P<0.01. Conclusion: The beneficial effects of the NP extract are related to its ability to decrease the levels of IL-1β and COX-2.

  5. Electroacupuncture improves cerebral blood flow and attenuates moderate ischemic injury via Angiotensin II its receptors-mediated mechanism in rats.

    Science.gov (United States)

    Li, Jing; He, Jiaojun; Du, Yuanhao; Cui, Jingjun; Ma, Ying; Zhang, Xuezhu

    2014-11-11

    To investigate the effects and potential mechanism of electroacupuncture intervention on expressions of Angiotensin II and its receptors-mediated signaling pathway in experimentally induced cerebral ischemia. Totally 126 male Wistar rats were randomly divided into control group, model group and EA group. The latter two were further divided into ten subgroups (n = 6) following Middle Cerebral Artery Occlusion (MCAO). Changes in regional cerebral blood flow (rCBF) and expressions of Angiotensin II and its receptors (AT1R, AT2R), as well as effector proteins in phosphatidyl inositol signal pathway were monitored before and at different times after MCAO. MCAO-induced decline of ipsilateral rCBF was partially suppressed by electroacupuncture, and contralateral blood flow was also superior to that of model group. Angiotensin II level was remarkably elevated immediately after MCAO, while electroacupuncture group exhibited significantly lower levels at 1 to 3 h and the value was significantly increased thereafter. The enhanced expression of AT1R was partially inhibited by electroacupuncture, while increased AT2R level was further induced. Electroacupuncture stimulation attenuated and postponed the upregulated-expressions of Gq and CaM these upregulations. ELISA results showed sharply increased expressions of DAG and IP3, which were remarkably neutralized by electroacupuncture. MCAO induced significant increases in expression of Angiotensin II and its receptor-mediated signal pathway. These enhanced expressions were significantly attenuated by electroacupuncture intervention, followed by reduced vasoconstriction and improved blood supply in ischemic region, and ultimately conferred beneficial effects on cerebral ischemia.

  6. S-nitrosoglutathione reduces tau hyper-phosphorylation and provides neuroprotection in rat model of chronic cerebral hypoperfusion.

    Science.gov (United States)

    Won, Je-Seong; Annamalai, Balasubramaniam; Choi, Seungho; Singh, Inderjit; Singh, Avtar K

    2015-10-22

    We have previously reported that treatment of rats subjected to permanent bilateral common carotid artery occlusion (pBCCAO), a model of chronic cerebral hypoperfusion (CCH), with S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, improved cognitive functions and decreased amyloid-β accumulation in the brains. Since CCH has been implicated in tau hyperphosphorylation induced neurodegeneration, we investigated the role of GSNO in regulation of tau hyperphosphorylation in rat pBCCAO model. The rats subjected to pBCCAO had a significant increase in tau hyperphosphorylation with increased neuronal loss in hippocampal/cortical areas. GSNO treatment attenuated not only the tau hyperphosphorylation, but also the neurodegeneration in pBCCAO rat brains. The pBCCAO rat brains also showed increased activities of GSK-3β and Cdk5 (major tau kinases) and GSNO treatment significantly attenuated their activities. GSNO attenuated the increased calpain activities and calpain-mediated cleavage of p35 leading to production of p25 and aberrant Cdk5 activation. In in vitro studies using purified calpain protein, GSNO treatment inhibited calpain activities while 3-morpholinosydnonimine (a donor of peroxynitrite) treatment increased its activities, suggesting the opposing role of GSNO vs. peroxynitrite in regulation of calpain activities. In pBCCAO rat brains, GSNO treatment attenuated the expression of inducible nitric oxide synthase (iNOS) expression and also reduced the brain levels of nitro-tyrosine formation, thereby indicating the protective role of GSNO in iNOS/nitrosative-stress mediated calpain/tau pathologies under CCH conditions. Taken together with our previous report, these data support the therapeutic potential of GSNO, a biological NO carrier, as a neuro- and cognitive-protective agent under conditions of CCH. Published by Elsevier B.V.

  7. Effect of fasting and different diets on 14C incorporation from U-14C glucose into glycogen and carbon dioxide by cerebral cortical slices of rats

    International Nuclear Information System (INIS)

    Visweswaran, P.; Binod Kumar; Sinha, A.P.; Suraiya, A.; Brahamchari, A.K.; Singh, S.P.

    1994-01-01

    There are some reports regarding change in the glycogen level due to fasting. Here an attempt is made by keeping the albino rats under fasting or feeding different diets on the rate of 14 C incorporation into glycogen and carbon dioxide from U- 14 C glucose. Our study reveals that the above conditions do not alter any significant change in the glycogen and carbon dioxide in the cerebral cortical slices of albino rats. (author). 8 refs., 1 tab

  8. Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres

    International Nuclear Information System (INIS)

    Yamakami, I.; McIntosh, T.K.

    1989-01-01

    To clarify the effect of experimental brain injury on regional CBF (rCBF), repeated rCBF measurements were performed using radiolabeled microspheres in rats subjected to fluid-percussion traumatic brain injury. Three consecutive microsphere injections in six uninjured control rats substantiated that the procedure induces no significant changes in hemodynamic variables or rCBF. Animals were subjected to left parietal fluid-percussion brain injury of moderate severity (2.1-2.4 atm) and rCBF values were determined (a) prior to injury and 15 min and 1 h following injury (n = 7); and (b) prior to injury and 30 min and 2 h following injury (n = 7). At 15 min post injury, there was a profound reduction of rCBF in all brain regions studied (p less than 0.01). Although rCBF in the hindbrain had recovered to near-normal by 30 min post injury, rCBF in both injured and contralateral (uninjured) forebrain areas remained significantly suppressed up to 1 h post injury. At 2 h post injury, recovery of rCBF to near-normal values was observed in all brain regions except the focal area of injury (left parietal cortex) where rCBF remained significantly depressed (p less than 0.01). This prolonged focal oligemia at the injury site was associated with the development of reproducible cystic necrosis in the left parietotemporal cortex at 4 weeks post injury. Our results demonstrate that acute changes in rCBF occur following experimental traumatic brain injury in rats and that rCBF remains significantly depressed up to 2 h post injury in the area circumscribing the trauma site

  9. Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats.

    Science.gov (United States)

    Mucio-Ramírez, Samuel; Makeyev, Oleksandr

    2017-01-01

    Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats ( n = 36) due to the single dose or five doses (given every 24 hours) of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals ( p  = 0.71). Moreover, it showed no statistically significant differences due to the number of stimulation doses ( p  = 0.71) nor due to the delay after the last stimulation dose ( p  = 0.96). Obtained results suggest that stimulation at current parameters (50 mA, 200  μ s, 300 Hz, biphasic, charge-balanced pulses for 2 minutes) does not induce neuronal damage in the hippocampal CA3 subregion of the brain.

  10. Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats

    Directory of Open Access Journals (Sweden)

    Samuel Mucio-Ramírez

    2017-01-01

    Full Text Available Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats (n=36 due to the single dose or five doses (given every 24 hours of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals (p = 0.71. Moreover, it showed no statistically significant differences due to the number of stimulation doses (p = 0.71 nor due to the delay after the last stimulation dose (p = 0.96. Obtained results suggest that stimulation at current parameters (50 mA, 200 μs, 300 Hz, biphasic, charge-balanced pulses for 2 minutes does not induce neuronal damage in the hippocampal CA3 subregion of the brain.

  11. Resveratrol alleviates cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy induction.

    Science.gov (United States)

    He, Qi; Li, Zhenyu; Wang, Yueting; Hou, Yanghao; Li, Lingyu; Zhao, Jing

    2017-09-01

    Resveratrol has been reported to protect against cerebral ischemia/reperfusion (I/R) injury in rats, but the underlying mechanism is unclear. In the current study, we examined whether resveratrol ameliorates cerebral I/R injury by inhibiting NLRP3 inflammasome-derived inflammation and whether autophagy is involved in this process. In addition, we explored the role of Sirt1 in resveratrol-mediated protective effects. To answer these questions, healthy male Sprague-Dawley rats were exposed to middle cerebral artery occlusion for 1h followed by 24h reperfusion. We found that cerebral I/R increased levels of activated NLRP3 inflammasome, caspase-1, IL-1β, and IL-18 and enhanced autophagy activity (ratio of LC3B-II/LC3B-I and p62/SQSTM1). Treatment with resveratrol, a specific Sirt1 agonist, attenuated I/R-induced NLRP3 inflammasome-derived inflammation but upregulated autophagy. Furthermore, resveratrol treatment clearly reduced cerebral infarct volume, decreased brain water content, and improved neurological scores. In addition, inhibition of autophagy using 3-MA intracerebroventricular injection blocked the inhibitory effect of resveratrol on NLRP3 inflammasome activation. Finally, Sirt1 knockdown with siRNA significantly blocked resveratrol-induced enhancement of autophagy activity and suppression of NLRP3 inflammasome activation. In conclusion, our results demonstrate that resveratrol protects against cerebral I/R injury by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy activity. Copyright © 2017. Published by Elsevier B.V.

  12. [Cerebral protection].

    Science.gov (United States)

    Cattaneo, A D

    1993-09-01

    Cerebral protection means prevention of cerebral neuronal damage. Severe brain damage extinguishes the very "human" functions such as speech, consciousness, intellectual capacity, and emotional integrity. Many pathologic conditions may inflict injuries to the brain, therefore the protection and salvage of cerebral neuronal function must be the top priorities in the care of critically ill patients. Brain tissue has unusually high energy requirements, its stores of energy metabolites are small and, as a result, the brain is totally dependent on a continuous supply of substrates and oxygen, via the circulation. In complete global ischemia (cardiac arrest) reperfusion is characterized by an immediate reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It has been postulated that the latter contributes to the ultimate neurologic outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by an area (ischemic penumbra) that is underperfused and contains neurotoxic substances such as free radicals, prostaglandins, calcium, and excitatory neurotransmitters. The variety of therapeutic effort that have addressed the question of protecting the brain reflects their limited success. 1) Barbiturates. After an initial enthusiastic endorsement by many clinicians and years of vigorous controversy, it can now be unequivocally stated that there is no place for barbiturate therapy following resuscitation from cardiac arrest. One presumed explanation for this negative statement is that cerebral metabolic suppression by barbiturates (and other anesthetics) is impossible in the absence of an active EEG. Conversely, in the event of incomplete ischemia EEG activity in usually present (albeit altered) and metabolic suppression and hence possibly protection can be induced with barbiturates. Indeed, most of the animal studies led to a number of recommendations for barbiturate therapy in man for incomplete ischemia. 2) Isoflurane. From a cerebral

  13. Panax ginseng extract attenuates neuronal injury and cognitive deficits in rats with vascular dementia induced by chronic cerebral hypoperfusion

    Directory of Open Access Journals (Sweden)

    Jun-De Zhu

    2018-01-01

    Full Text Available Panax ginseng is a slow-growing perennial plant. Panax ginseng extract has numerous biological activities, including antitumor, anti-inflammatory and antistress activities. Panax ginseng extract also has a cognition-enhancing effect in rats with alcohol-induced memory impairment. In this study, we partially occluded the bilateral carotid arteries in the rat to induce chronic cerebral hypoperfusion, a well-known model of vascular dementia. The rats were then intragastrically administered 50 or 100 mg/kg Panax ginseng extract. Morris water maze and balance beam tests were used to evaluate memory deficits and motor function, respectively. Protein quantity was used to evaluate cholinergic neurons. Immunofluorescence staining was used to assess the number of glial fibrillary acidic protein-positive cells. Western blot assay was used to evaluate protein levels of vascular endothelial growth factor, basic fibroblast growth factor, Bcl-2 and Bax. Treatment with Panax ginseng extract for 8 weeks significantly improved behavioral function and increased neuronal density and VEGF and bFGF protein expression in the hippocampal CA3 area. Furthermore, Panax ginseng extract reduced the number of glial fibrillary acidic protein-immunoreactive cells, and it decreased apoptosis by upregulating Bcl-2 and downregulating Bax protein expression. The effect of Panax ginseng extract was dose-dependent and similar to that of nimodipine, a commonly used drug for the treatment of vascular dementia. These findings suggest that Panax ginseng extract is neuroprotective against vascular dementia induced by chronic cerebral hypoperfusion, and therefore might have therapeutic potential for preventing and treating the disease.

  14. A comparison of long-term functional outcome after 2 middle cerebral artery occlusion models in rats.

    Science.gov (United States)

    Roof, R L; Schielke, G P; Ren, X; Hall, E D

    2001-11-01

    Proven behavioral assessment strategies for testing potential therapeutic agents in rat stroke models are needed. Few studies include tasks that demand higher levels of sensorimotor and cognitive function. Because behavioral outcome and rate of recovery vary among ischemia models, there is a need to characterize and compare performance on specific tasks across models. To this end, sensorimotor and cognitive deficits were assessed during a 5-week period after either permanent proximal middle cerebral artery occlusion (pMCAO) or permanent distal middle cerebral artery occlusion combined with a 90-minute occlusion of both common carotid arteries (dMCAO/tCCAO) in Sprague-Dawley rats. The EBST, hindlimb and forelimb placing, and cylinder tests were given at regular intervals postinjury to assess sensorimotor function. Cognitive function was assessed with a multitrial water navigation task. pMCAO, which caused both striatal and cortical damage, produced persistent sensorimotor and cognitive deficits. Limb placing responses and postural reflexes were impaired throughout the month of testing. A persistent bias for using the ipsilateral forelimb for wall movements in the cylinder test was observed as well as a bias for landing on the opposite forelimb. pMCAO rats were also impaired in the water navigation task. dMCAO/tCCAO, which caused only cortical damage, produced similar sensorimotor deficits, but these were greatly diminished by 2 weeks after injury. No impairment was found for water tank navigation. Correlations between forelimb placing (both models), water navigation performance (pMCAO model), and sensorimotor asymmetry (dMCAOtCCAO model) and infarct volume were observed. Based on the range of functions affected and stability of observed deficits, the pMCAO model appears to be preferable to the dMCAO/tCCAO model for use in assessing therapeutic agents for stroke.

  15. Monitoring stem cell transplantation in rat cerebral ischemic infarction model with 131I-FIAU/TK reporter gene system

    International Nuclear Information System (INIS)

    Wu Tao; An Rui; Zhang Binqing; Sun Xun; Lang Juntao

    2011-01-01

    Objective: To study the biodistribution of 131 I-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil (FIAU) in the rat middle cerebral artery occlusion model and the expression of thymidine kinase (TK) gene in brain tissue after gene-modified stem cell transplantation, and thus evaluate the possibility of further noninvasive monitoring of stem cell transplantation therapy in cerebral infarction. Methods: Adenovirus recombinant Ad5-TK-internal ribosome entry site-brain derived heterotrophic factor-enhanced green florescent protein(IRES-BDNF-EGFP) carrying TK-IRES-BDNF gene was prepared. Cerebral infarction model was established in rats by intraluminal middle cerebral artery occlusion with nylon monofilament. Gene modified bone marrow mesenchymal stem cells were transplanted via intraparenchymal route, lateral ventricle, carotid artery and tail vein, respectively. The normal rats were used as controls. 131 I-FAU was prepared to be the tracer for biodistribution study and the % ID/g was calculated based on measurement of the tissue radioactivity counts. The expression of TK gene was evaluated by quantitative real-time PCR (QR-PCR) and Western blot analysis. Data were analyzed with independent-samples t-test, one-way analysis of variance (ANOVA) test, and Pearson linear correlation test. Results: The % ID/g of infarcted brain tissue in the intraparenchymal group was 0.124 ± 0.013, which was significantly higher than that in lateral ventricle group (0.052 ±0.004), carotid artery group (0.061 ±0.002), tail vein group (0.059 ±0.005) and control group (0.005 ±0.001) (t=2.913-5.652, all P<0.05), while there were no statistically significant differences among the other route transplanted groups (t=0.694-1.448, all P>0.05). The differences of % ID/g between the infarcted and contralateral sides of brain tissue in all transplanted groups were statistically significant (t=9.004-15.734, all P<0.05), while there was no statistically significant difference of this parameter

  16. Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats - A possible new hydrogen resource for clinical use.

    Science.gov (United States)

    Cui, Jin; Chen, Xiao; Zhai, Xiao; Shi, Dongchen; Zhang, Rongjia; Zhi, Xin; Li, Xiaoqun; Gu, Zhengrong; Cao, Liehu; Weng, Weizong; Zhang, Jun; Wang, Liping; Sun, Xuejun; Ji, Fang; Hou, Jiong; Su, Jiacan

    2016-10-29

    Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically. Copyright © 2016. Published by Elsevier Ltd.

  17. Nitric oxide (NO) is an endogenous anticonvulsant but not a mediator of the increase in cerebral blood flow accompanying bicuculline-induced seizures in rats

    DEFF Research Database (Denmark)

    Wang, Qian; Theard, M A; Pelligrino, D A

    1994-01-01

    ) is NO an endogenous anticonvulsant or proconvulsant substance? and (2) is the cerebral blood flow (CBF) increase accompanying bicuculline (BC)-induced seizures mediated by NO? The experiments were performed in 300-400-g Wistar rats anesthetized with 0.6% halothane and 70% N2O/30% O2. CBF was measured using...

  18. Beta-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex: Reversal by NMDA receptor blockade : Reversal by NMDA receptor blockade

    NARCIS (Netherlands)

    O’Mahony, S.; Harkany, T.; Ábrahám, I.; Jong, G.I. de; Varga, J.L.; Zarándi, M.; Penke, B.; Nyakas, C.; Luiten, P.G.M.; Leonard, B.E.

    1998-01-01

    Ample experimental evidence indicates that acute beta-amyloid infusion into the nucleus basalis of rats elicits abrupt degeneration of the magnocellular cholinergic neurons projecting to the cerebral cortex, In fact, involvement of a permanent Ca2+ overload, partially via N-methyl-D-aspartate (NMDA)

  19. Cerebrovascular endothelin-1 hyper-reactivity is associated with transient receptor potential canonical channels 1 and 6 activation and delayed cerebral hypoperfusion after forebrain ischaemia in rats

    DEFF Research Database (Denmark)

    Johansson, S E; Andersen, X E D R; Hansen, R H

    2015-01-01

    . METHODS: Experimental forebrain ischaemia was induced in Wistar male rats by a two-vessel occlusion model, and the cerebral blood flow was measured by magnetic resonance imaging two days after reperfusion. In vitro vasoreactivity studies, immunofluorescence and quantitative PCR were performed on cerebral...... in the vascular smooth muscle cells was enhanced and correlated with decreased cerebral blood flow two days after forebrain ischaemia. Furthermore, under conditions when voltage-dependent calcium channels were inhibited, endothelin-1-induced cerebrovascular contraction was enhanced and this enhancement...... was presumably mediated by Ca(2+) influx via upregulated transient receptor potential canonical channels 1 and 6. CONCLUSIONS: Our data demonstrates that endothelin-1-mediated influx of extracellular Ca(2+) activates transient receptor potential canonical channels 1 and 6 in cerebral vascular smooth muscle cells...

  20. Anti neuroinflammatory effect of Vildagliptin in ischaemia-reperfusion induced cerebral infarction in normal and STZ induced type-II diabetic rats

    Directory of Open Access Journals (Sweden)

    Kaleru Purnachander

    2016-03-01

    Full Text Available Diabetes is one of the major risk factor for cerebral ischemic stroke. Increased base line levels of oxidative stress in diabetes will lead to cerebral ischemic damage. In pathological conditions such as cerebral ischemia/reperfusion injury, free radicals cause oxidative stress and inflammation leading to increased injury of brain. Inflammation is one of the major pathological mechanisms involved in cerebral ischemia and reperfusion injury. Vildagliptin newer anti-diabetic drug of the class DPP-4 inhibitors is reported to have anti-inflammatory properties apart from its antihyperglycemic activity. Therefore the aim of the present study is to evaluate the anti-inflammatory effect of Vildagliptin against cerebral infarction induced ischemia reperfusion injury in normal and STZ induced diabetic Wistar rats. Cerebral infarction was induced by bilateral common carotid artery occlusion followed by 4 hr reperfusion. Percent infarction, inflammatory markers such as MPO, TNF-α, IL-6 and IL-10 were analysed. Treatment with Vildagliptin for a period of four weeks produced significant reduction in percent cerebral infarct volume. Vildagliptin at 10 mg/kg dose, showed significant reduction in markers like MPO, TNF-α, IL-6 and IL-1β in diabetic group when compared to normal group and in contrast significant increase in anti-inflammatory marker like IL-10 levels. Vildagliptin showed significant cerebroprotective effect by antiinflammatory mechanisms.

  1. Contribution of oxygen-sensitive neurons of the rostral ventrolateral medulla to hypoxic cerebral vasodilatation in the rat

    Science.gov (United States)

    Golanov, E. V.; Reis, D. J.

    1996-01-01

    1. We sought to determine whether hypoxic stimulation of neurons of the rostral ventrolateral reticular nucleus (RVL) would elevate regional cerebral blood flow (rCBF) in anaesthetized paralysed rats. 2. Microinjection of sodium cyanide (NaCN; 150-450 pmol) into the RVL rapidly (within 1-2 s), transiently, dose-dependently and site-specifically elevated rCBF1 measured by laser Doppler flowmetry, by 61.3 +/- 22.1% (P < 0.01), increased arterial pressure (AP; +30 +/- 8 mmHg; P < 0.01)1 and triggered a synchronized 6 Hz rhythm of EEG activity. 3. Following cervical spinal cord transection, NaCN and also dinitrophenol (DNP) significantly (P < 0.05) elevated rCBF and synchronized the EEG but did not elevate AP; the response to NaCN was attenuated by hyperoxia and deepening of anaesthesia. 4. Electrical stimulation of NaCN-sensitive sites in the RVL in spinalized rats increased rCBF measured autoradiographically with 14C iodoantipyrine (Kety method) in the mid-line thalamus (by 182.3 +/- 17.2%; P < 0.05) and cerebral cortex (by 172.6 +/- 15.6%; P < 0.05) regions, respectively, directly or indirectly innervated by RVL neurons, and in the remainder of the brain. In contrast regional cerebral glucose utilization (rCGU), measured autoradiographically with 14C-2-deoxyglucose (Sokoloff method), was increased in proportion to rCBF in the mid-line thalamus (165.6 +/- 17.8%, P < 0.05) but was unchanged in the cortex. 5. Bilateral electrolytic lesions of NaCN sensitive sites of RVL, while not altering resting rCBF or the elevation elicited by hypercarbia (arterial CO2 pressure, Pa,CO2, approximately 69 mmHg), reduced the vasodilatation elicited by normocapnic hypoxaemia (arterial O2 pressure, Pa,O2, approximately 27 mmHg) by 67% (P < 0.01) and flattened the slope of the Pa,O2-rCBF response curve. 6. We conclude that the elevation of rCBF produced in the cerebral cortex by hypoxaemia is in large measure neurogenic, mediated trans-synaptically over intrinsic neuronal pathways, and

  2. Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute NO-deficiency in rats.

    Directory of Open Access Journals (Sweden)

    Béla Horváth

    Full Text Available BACKGROUND: Low frequency (4-12 cpm spontaneous fluctuations of the cerebrovascular tone (vasomotion and oscillations of the cerebral blood flow (CBF have been reported in diseases associated with endothelial dysfunction. Since endothelium-derived nitric oxide (NO suppresses constitutively the release and vascular effects of thromboxane A(2 (TXA(2, NO-deficiency is often associated with activation of thromboxane receptors (TP. In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations. METHODOLOGY/PRINCIPAL FINDINGS: Effects of pharmacological modulation of TP-receptor activation and its downstream signaling pathway have been investigated on CBF oscillations (measured by laser-Doppler flowmetry in anesthetized rats and vasomotion (measured by isometric tension recording in isolated rat middle cerebral arteries, MCAs both under physiological conditions and after acute inhibition of NO synthesis. Administration of the TP-receptor agonist U-46619 (1 µg/kg i.v. to control animals failed to induce any changes of the systemic or cerebral circulatory parameters. Inhibition of the NO synthesis by nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.v. resulted in increased mean arterial blood pressure and a decreased CBF accompanied by appearance of CBF-oscillations with a dominant frequency of 148±2 mHz. U-46619 significantly augmented the CBF-oscillations induced by L-NAME while inhibition of endogenous TXA(2 synthesis by ozagrel (10 mg/kg i.v. attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 µM Y-27632. CONCLUSION/SIGNIFICANCE: These results suggest that hypersensitivity of the TP

  3. Biphasic functional regulation in hippocampus of rat with chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid artery.

    Directory of Open Access Journals (Sweden)

    Jihye Bang

    Full Text Available BACKGROUND: Chronic cerebral hypoperfusion induced by permanent occlusion of the bilateral common carotid artery (BCCAO in rats has been commonly used for the study of Alzheimer's disease and vascular dementia. Despite the apparent cognitive dysfunction in rats with BCCAO, the molecular markers or pathways involved in the pathological alternation have not been clearly identified. METHODS: Temporal changes (sham, 21, 35, 45, 55 and 70 days in gene expression in the hippocampus of rats after BCCAO were measured using time-course microarray analysis. Gene Ontology (GO and pathway analyses were performed to identify the functional involvement of temporally regulated genes in BCCAO. RESULTS: Two major gene expression patterns were observed in the hippocampus of rats after BCCAO. One pattern, which was composed of 341 early up-regulated genes after the surgical procedure, was dominantly involved in immune-related biological functions (false discovery rate [FDR]<0.01. Another pattern composed of 182 temporally delayed down-regulated genes was involved in sensory perception such as olfactory and cognition functions (FDR<0.01. In addition to the two gene expression patterns, the temporal change of GO and the pathway activities using all differentially expressed genes also confirmed that an immune response was the main early change, whereas sensory functions were delayed responses. Moreover, we identified FADD and SOCS3 as possible core genes in the sensory function loss process using text-based mining and interaction network analysis. CONCLUSIONS: The biphasic regulatory mechanism first reported here could provide molecular evidence of BCCAO-induced impaired memory in rats as well as mechanism of the development of vascular dementia.

  4. Effects of regional cerebral blood flow perfusion on learning and memory function and its molecular mechanism in rats

    Institute of Scientific and Technical Information of China (English)

    Cunli Xu; Wenhua Wu; Lingbin Kong

    2016-01-01

    Objective:To study the effects of regional cerebral blood flow (rCBF) perfusion on learning and memory function in special brain areas and its molecular mechanism in rat. Methods: Sixty-four adult male healthy Sprague-Dawley (SD) rats were randomly divided into two groups: Afalse operation group and an operation group. The false operation group was randomly divided into four subgroups (A0, B0, C0, and D0) and the operation group was randomly divided into four subgroups (A, B, C, and D), with eight rats in each subgroup. The operation group underwent bilateral common carotid artery permanent ligation, while the other group only underwent a skin incision without the bilateral common carotid artery permanent ligation. Learning memory function of rats in each subgroup was measured using a Y-maze at 4 h, 8 h, 24 h, and 3 days after surgery. The rCBF in the right frontal lobe and hippocampus was detected using the Periflux PF model laser Doppler flowmetry and c-fos, c-jun, Bcl-2, and Bax protein expression in the right frontal lobe and hippocampus was measured using immunohistochemistry. Results: The rCBF in the right frontal lobule division and right hippocampus division was significantly lower in the operation group than in the false operation group (P Conclusions:rCBF decrease can impair learning and memory function in rats, which may be related to the increased expression of c-fos, c-jun, Bcl-2, and Bax proteins in the frontal cortex and hippocampus.

  5. Protective effects of repetitive transcranial magnetic stimulation in a rat model of transient cerebral ischaemia: a microPET study

    International Nuclear Information System (INIS)

    Gao, Feng; Wang, Shuang; Guo, Yi; Lou, Min; Wu, Jimin; Ding, Meiping; Wang, Jing; Zhang, Hong; Tian, Mei

    2010-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method to excite neurons in the brain. However, the underlying mechanism of its therapeutic effects in stroke remains unclear. The aim of this study was to investigate the neuroprotective effect of high-frequency rTMS in a rat model of transient cerebral ischaemia using positron emission tomography (PET). Sprague-Dawley rats (n=30) were anaesthetized with chloral hydrate and subjected to 90 min of intraluminal middle cerebral artery occlusion (MCAO) with subsequent reperfusion in three groups: control (n=10), rTMS (n=10), or sham-rTMS groups (n=10). In the rTMS group, rTMS was given 1 h after ischaemia and every 24 h for 7 days after MCAO. In all three groups, small-animal PET (microPET) imaging with 18 F-FDG was used to evaluate brain glucose metabolism. Apoptotic molecules were measured in the infarct margin using immunohistochemical staining. The neurological scores of the rats in the rTMS group were higher than in those of the control group over the whole 7-day observation period. The total, cortical and striatal infarct volumes were significantly less in the rTMS group than in the control group, as measured by 2,3,5-triphenyltetrazolium chloride staining. 18 F-FDG microPET images showed significantly higher standardized uptake values in the cortex and striatum in the rTMS group than in the control group in the affected hemisphere. The number of cells positive for caspase-3 was significantly lower in the rTMS group than in the control group, while the Bcl-2/Bax ratio was significantly higher in the rTMS group than in the control group. rTMS therapy increased glucose metabolism and inhibited apoptosis in the ischaemic hemisphere. 18 F-FDG PET could be used to monitor rTMS therapy in transient cerebral ischaemia in animal studies and in future clinical trials. (orig.)

  6. Protective effects of repetitive transcranial magnetic stimulation in a rat model of transient cerebral ischaemia: a microPET study

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Feng [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Neurology, Hangzhou, Zhejiang (China); Zhejiang University Medical PET Center, Hangzhou, Zhejiang (China); Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, Zhejiang (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, Zhejiang (China); Wang, Shuang; Guo, Yi; Lou, Min; Wu, Jimin; Ding, Meiping [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Neurology, Hangzhou, Zhejiang (China); Wang, Jing; Zhang, Hong [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Zhejiang University Medical PET Center, Hangzhou, Zhejiang (China); Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, Zhejiang (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, Zhejiang (China); Tian, Mei [The University of Texas M.D. Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

    2010-05-15

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method to excite neurons in the brain. However, the underlying mechanism of its therapeutic effects in stroke remains unclear. The aim of this study was to investigate the neuroprotective effect of high-frequency rTMS in a rat model of transient cerebral ischaemia using positron emission tomography (PET). Sprague-Dawley rats (n=30) were anaesthetized with chloral hydrate and subjected to 90 min of intraluminal middle cerebral artery occlusion (MCAO) with subsequent reperfusion in three groups: control (n=10), rTMS (n=10), or sham-rTMS groups (n=10). In the rTMS group, rTMS was given 1 h after ischaemia and every 24 h for 7 days after MCAO. In all three groups, small-animal PET (microPET) imaging with {sup 18}F-FDG was used to evaluate brain glucose metabolism. Apoptotic molecules were measured in the infarct margin using immunohistochemical staining. The neurological scores of the rats in the rTMS group were higher than in those of the control group over the whole 7-day observation period. The total, cortical and striatal infarct volumes were significantly less in the rTMS group than in the control group, as measured by 2,3,5-triphenyltetrazolium chloride staining. {sup 18}F-FDG microPET images showed significantly higher standardized uptake values in the cortex and striatum in the rTMS group than in the control group in the affected hemisphere. The number of cells positive for caspase-3 was significantly lower in the rTMS group than in the control group, while the Bcl-2/Bax ratio was significantly higher in the rTMS group than in the control group. rTMS therapy increased glucose metabolism and inhibited apoptosis in the ischaemic hemisphere. {sup 18}F-FDG PET could be used to monitor rTMS therapy in transient cerebral ischaemia in animal studies and in future clinical trials. (orig.)

  7. Exercise preconditioning improves behavioral functions following transient cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats.

    Science.gov (United States)

    Tahamtan, Mahshid; Allahtavakoli, Mohammad; Abbasnejad, Mehdi; Roohbakhsh, Ali; Taghipour, Zahra; Taghavi, Mohsen; Khodadadi, Hassan; Shamsizadeh, Ali

    2013-12-01

    There is evidence that exercise decreases ischemia/reperfusion injury in rats. Since behavioral deficits are the main outcome in patients after stroke, our study was designed to investigate whether exercise preconditioning improves the acute behavioral functions and also brain inflammatory injury following cerebral ischemia. Male rats weighing 250-300 g were randomly allocated into five experimental groups. Exercise was performed on a treadmill 30min/day for 3 weeks. Ischemia was induced by 4-vessel occlusion method. Recognition memory was assessed by novel object recognition task (NORT) and step-through passive avoidance task. Sensorimotor function and motor movements were evaluated by adhesive removal test and ledged beam-walking test, respectively. Brain inflammatory injury was evaluated by histological assessment. In NORT, the discrimination ratio was decreased after ischemia (P test, a significant reduction in response latency was observed in the ischemic group. Exercise preconditioning significantly decreased the response latency in the ischemic rats (P test, latency to touch and remove the sticky labels from forepaw was increased following induction of ischemia (all P beam-walking test, the slip ratio was increased following ischemia (P < 0.05).  In the ischemia group, marked neuronal injury in hippocampus was observed. These neuropathological changes were attenuated by exercise preconditioning (P < 0.001). Our results showed that exercise preconditioning improves behavioral functions and maintains more viable cells in the dorsal hippocampus of the ischemic brain.

  8. Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle

    Directory of Open Access Journals (Sweden)

    Valenti Vitor E

    2012-03-01

    Full Text Available Abstract Background Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxida