scholarly journals Dose Effect Evaluation and Therapeutic Window of the Neuro-EPO Nasal Application for the Treatment of the Focal Ischemia Model in the Mongolian Gerbil

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Iliana Sosa Teste ◽  
Yuneidys Mengana Tamos ◽  
Yamila Rodríguez Cruz ◽  
Adriana Muñoz Cernada ◽  
Janette Cruz Rodríguez ◽  
...  
Keyword(s):  
Brain Ischemia ◽  
Mongolian Gerbil ◽  
Neuroprotective Effect ◽  
Developed Countries ◽  
Focal Ischemia ◽  
Exploratory Activity ◽  
Dose Effect ◽  
Therapeutic Window ◽  
Average Dose ◽  
Thalamic Nuclei

Cerebrovascular disease is the third leading cause of death and the leading cause of disability in Cuba and in several developed countries. A possible neuroprotective agent is the rHu-EPO, whose effects have been demonstrated in models of brain ischemia. The Neuro-EPO is a derivative of the rHu-EPO that avoids the stimulation of erythropoiesis. The aim of this study was to determine the Neuro-EPO delivery into the central nervous system (CNS) to exert a neuroprotective effect in cerebral ischemia model of the Mongolian gerbil. The Neuro-EPO in a rate of 249.4 UI every 8 hours for 4 days showed 25% higher viability efficacy (), improving neurological score and behavior of the spontaneous exploratory activity, the preservation of CA3 areas of the hippocampus, the cortex, and thalamic nuclei in the focal ischemia model of the Mongolian gerbil. In summary, this study, the average dose-used Neuro-EPO (249.4 UI/10 μL/every 8 hours for 4 days), proved to be valid indicators of viability, neurological status, and spontaneous exploratory activity, being significantly lower than that reported for the systemically use of the rHu-EPO as a neuroprotectant. Indeed, up to 12 h after brain ischemia is very positive Neuro-EPO administration by the nasal route as a candidate for neuroprotection.

scholarly journals Neuroprotective effect of mild hypothermia in the temporary brain ischemia in cats

2007 ◽  
Vol 65 (3b) ◽  
pp. 810-815 ◽  
Author(s):  
Hiroshi Nakano ◽  
Benedicto Oscar Colli ◽  
Luiza da Silva Lopes
Keyword(s):  
Basal Ganglia ◽  
Brain Ischemia ◽  
Mild Hypothermia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Focal Ischemia ◽  
Volume Calculation ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

OBJECTIVE: To evaluate the neuroprotective effect of mild hypothermia during temporary focal ischemia in cats. METHOD: 20 cats underwent middle cerebral artery 60 minutes occlusion and 24 hours reperfusion: 10 under normothermia and 10 under mild hypothermia (32º C). Brain coronal sections 2mm thick were stained with 2,3,5-triphenyltetrazolium hydrochloride, photographed and evaluated with software for volume calculation. RESULTS:Cortical ischemia was found in 7 and basal ganglia ischemia in 8 animals of group 1 and in both regions in 5 animals of group 2 (no difference: p=0.6499 for cortical; p=0.3498 for basal ganglia). No ischemia was found in 5 animals of group 2 and in none of group 1 (significant difference, p=0.0325). The infarct volume was greater in group 1 than 2 (p=0.0433). CONCLUSION: Mild hypothermia did not interfere with location of ischemia, but it was effective for reducing the infarct volume.

scholarly journals Evaluation of the neuroprotective effect of ketoprofen on rats submitted to permanent focal brain ischemia

2007 ◽  
Vol 65 (4a) ◽  
pp. 978-984 ◽  
Author(s):  
Manoel Nunes da Silva ◽  
Benedicto Oscar Colli ◽  
Norberto Cysne Coimbra ◽  
Joaquim Coutinho Netto
Keyword(s):  
Brain Ischemia ◽  
Sham Group ◽  
Neuroprotective Effect ◽  
Exploratory Activity ◽  
Left Middle Cerebral Artery ◽  
Histopathological Changes ◽  
Total Brain ◽  
Focal Brain Ischemia ◽  
Left Middle ◽  
Neuroprotective Action

OBJECTIVE: To study the neurobehavioral, biochemical and histopathological consequences of permanent focal brain ischemia, and the putative neuroprotective action of ketoprofen. METHOD: One-hundred-and-three Wistar rats divided into groups A and B were respectively submitted to 48 hours and 15 days of ischemia. Each group was divided into 4 subgroups: ischemic not treated, ischemic treated, sham not treated, and sham treated. Ischemic animals had the left middle cerebral artery coagulated. Ketoprofen was administered to treated subgroups 15 minutes before arterial coagulation (manipulation in the sham group). RESULTS: Exploratory activity and defecation were reduced in all ischemic animals in the first postoperative days and constant histopathological changes were observed in each group. The total brain glutamate levels were higher in treated animals 48 hours after surgery. CONCLUSION: No clear parallelism among behavioral, biochemical and histopathological findings was observed. Ketoprofen demonstrated no neuroprotective effect on the behavioral or histopathological aspects of focal permanent brain ischemia.

scholarly journals Intratympanic steroid therapy for Bell’s palsy with poor prognostic results

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akira Inagaki ◽  
Sachiyo Katsumi ◽  
Shinji Sekiya ◽  
Shingo Murakami
Keyword(s):  
Facial Nerve ◽  
Steroid Therapy ◽  
Standard Dose ◽  
Neuroprotective Effect ◽  
Bell’S Palsy ◽  
Control Group ◽  
Average Dose ◽  
Test Results ◽  
Bell's Palsy ◽  
Intratympanic Dexamethasone

AbstractIn Bell’s palsy, electrodiagnosis by electroneurography (ENoG) is widely used to predict a patient’s prognosis. The therapeutic options for patients with poor prognostic results remain controversial. Here, we investigated whether early intervention with intratympanic steroid therapy (ITST) is an effective treatment for Bell’s palsy patients with poor electrodiagnostic test results (≤ 10% electroneurography value). Patients in the concurrent ITST group (n = 8) received the standard systemic dose of prednisolone (410 mg total) and intratympanic dexamethasone (16.5 mg total) and those in the control group (n = 21) received systemic prednisolone at the standard dose or higher (average dose, 605 ± 27 mg). A year after onset, the recovery rate was higher in the ITST group than in the control group (88% vs 43%, P = 0.044). The average House-Brackmann grade was better in the concurrent ITST group (1.13 ± 0.13 vs 1.71 ± 0.16, P = 0.035). Concurrent ITST improves the facial nerve outcome in patients with poor electroneurography test results, regardless of whether equivalent or lower glucocorticoid doses were administered. This may be ascribed to a neuroprotective effect of ITST due to a higher dose of steroid reaching the lesion due to dexamethasone transfer in the facial nerve.

scholarly journals The hypoxia sensitive metal transcription factor MTF-1 activates NCX1 brain promoter and participates in remote postconditioning neuroprotection in stroke

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Valeria Valsecchi ◽  
Giusy Laudati ◽  
Ornella Cuomo ◽  
Rossana Sirabella ◽  
Lucio Annunziato ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Brain Ischemia ◽  
Femoral Artery ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Sodium Calcium Exchanger ◽  
Protein Levels ◽  
Relevant Role ◽  
Remote Postconditioning

AbstractRemote limb ischemic postconditioning (RLIP) is an experimental strategy in which short femoral artery ischemia reduces brain damage induced by a previous harmful ischemic insult. Ionic homeostasis maintenance in the CNS seems to play a relevant role in mediating RLIP neuroprotection and among the effectors, the sodium-calcium exchanger 1 (NCX1) may give an important contribution, being expressed in all CNS cells involved in brain ischemic pathophysiology. The aim of this work was to investigate whether the metal responsive transcription factor 1 (MTF-1), an important hypoxia sensitive transcription factor, may (i) interact and regulate NCX1, and (ii) play a role in the neuroprotective effect mediated by RLIP through NCX1 activation. Here we demonstrated that in brain ischemia induced by transient middle cerebral occlusion (tMCAO), MTF-1 is triggered by a subsequent temporary femoral artery occlusion (FAO) and represents a mediator of endogenous neuroprotection. More importantly, we showed that MTF-1 translocates to the nucleus where it binds the metal responsive element (MRE) located at −23/−17 bp of Ncx1 brain promoter thus activating its transcription and inducing an upregulation of NCX1 that has been demonstrated to be neuroprotective. Furthermore, RLIP restored MTF-1 and NCX1 protein levels in the ischemic rat brain cortex and the silencing of MTF-1 prevented the increase of NCX1 observed in RLIP protected rats, thus demonstrating a direct regulation of NCX1 by MTF-1 in the ischemic cortex of rat exposed to tMCAO followed by FAO. Moreover, silencing of MTF-1 significantly reduced the neuroprotective effect elicited by RLIP as demonstrated by the enlargement of brain infarct volume observed in rats subjected to RLIP and treated with MTF-1 silencing. Overall, MTF-dependent activation of NCX1 and their upregulation elicited by RLIP, besides unraveling a new molecular pathway of neuroprotection during brain ischemia, might represent an additional mechanism to intervene in stroke pathophysiology.

Treatment of embolic stroke in rats with bortezomib and recombinant human tissue plasminogen activator

2006 ◽  
Vol 95 (01) ◽  
pp. 166-173 ◽  
Author(s):  
Li Zhang ◽  
Zheng Zhang ◽  
Xianshuang Liu ◽  
Ann Hozeska ◽  
Nancy Stagliano ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Vascular Function ◽  
Inflammatory Responses ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Therapeutic Window ◽  
Vascular Events ◽  
Tissue Plasminogen

SummaryStroke elicits a progressive vascular dysfunction, which contributes to the evolution of brain injury. Thrombolysis with tissue plasminogen activator (tPA) promotes adverse vascular events that limit the therapeutic window of stroke to three hours. Proteasome inhibitors reduce vascular thrombotic and inflammatory events, and consequently protect vascular function. The present study evaluated the neuroprotective effect of bortezomib,a potent and selective inhibitor of the proteasome, alone and in combination with delayed thrombolytic therapy on a rat model of embolic focal cerebral ischemia. Treatment with bortezomib reduces adverse cerebrovascular events including secondary thrombosis,inflammatory responses,and blood brain barrier (BBB) disruption, and hence reduces infarct volume and neurological functional deficit when administrated within 4 h after stroke onset. Combination of bortezomib and tPA extends the thrombolytic window for stroke to6 h, which is associated with the improvement of vascular patency and integrity. Real time RT-PCR of endothelial cells isolated by laser-capture microdissection from brain tissue and Western blot analysis showed that bortezomib upregulates endothelial nitric oxide synthase (eNOS) expression and blocks NF-κB activation. These results demonstrate that bortezomib promotes eNOS dependent vascular protection, and reduces NF-κB dependent vascular disruption, all of which may contribute to neuroprotection after stroke.

scholarly journals Transplantation of human neural stem/progenitor cells overexpressing galectin-1 improves functional recovery from focal brain ischemia in the mongolian gerbil

2011 ◽  
Vol 4 (1) ◽  
pp. 35 ◽  
Author(s):  
Junichi Yamane ◽  
Satoru Ishibashi ◽  
Masanori Sakaguchi ◽  
Toshihiko Kuroiwa ◽  
Yonehiro Kanemura ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Brain Ischemia ◽  
Functional Recovery ◽  
Mongolian Gerbil ◽  
Neural Stem Progenitor Cells ◽  
Focal Brain Ischemia

scholarly journals The Two Pathophysiologies of Focal Brain Ischemia: Implications for Translational Stroke Research

2012 ◽  
Vol 32 (7) ◽  
pp. 1310-1316 ◽  
Author(s):  
Konstantin-Alexander Hossmann
Keyword(s):  
Vascular Occlusion ◽  
Maximum Size ◽  
Focal Ischemia ◽  
Therapeutic Window ◽  
Stroke Research ◽  
Naturally Occurring ◽  
Free Interval ◽  
Postischemic Recirculation ◽  
Primary Core ◽  
Focal Brain Ischemia

Brain injury after focal ischemia evolves along two basically different pathophysiologies, depending on the severity of the primary flow reduction and the dynamics of postischemic recirculation. In permanent and gradually reversed focal ischemia as after thromboembolic occlusion, primary core injury is irreversible but the expansion of the core into the penumbra can be alleviated by hemodynamic and molecular interventions. Such alleviation can only be achieved within 3 hours after the onset of ischemia because untreated core injury expands to near maximum size during this interval. In promptly reversed transient ischemia as after mechanical vascular occlusion, primary core injury may recover but a secondary delayed injury evolves after a free interval of as long as 6 to 12 hours. This injury can be alleviated throughout the free interval but the longer window is without clinical relevance because transient mechanical vascular occlusion is not a model of naturally occurring stroke. As this difference is widely ignored in stroke research, most clinical trials have been designed with a far too long therapeutic window, which explains their failure. Transient mechanical vascular occlusion models should, therefore, be eliminated from the repertoire of preclinical stroke research.

Neuroprotective effect of immunosuppressant FK506 in transient focal ischemia in rats: Therapeutic time window for FK506 in transient focal ischemia

2001 ◽  
Vol 23 (7) ◽  
pp. 755-760 ◽  
Author(s):  
Takako Arii ◽  
Tatsushi Kamiya ◽  
Kazumasa Arii ◽  
Masayuki Ueda ◽  
Chikako Nito ◽  
...  
Keyword(s):  
Time Window ◽  
Neuroprotective Effect ◽  
Focal Ischemia ◽  
Transient Focal Ischemia ◽  
Therapeutic Time Window
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