Neurological impairment in rats after transient middle cerebral artery occlusion: a comparative study under various treatment paradigms

Zausinger, Stefan; Hungerhuber, Edwin; Baethmann, A.; Reulen, Hanns-Jürgen; Schmid-Elsaesser, Robert

doi:10.1016/s0006-8993(00)02100-4

Cited by 201 publications

(116 citation statements)

References 59 publications

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“…Behavioral impairment following MCAO was assessed at 30 minutes after ischemic surgery when animals had recovered from the anesthetic and 24 hours after reperfusion by 2 investigators blind to the treatment of the mice. A modified 6-point scale was used (25,26): 0, normal; 1, mild turning behavior with or without inconsistent curling when picked up by tail and less than 50% attempts to curl to the contralateral side; 2, mild, consistent curling and more than 50% attempts to curl to the contralateral side; 3, strong and immediate consistent curling, mouse holds curled position for more than 1-2 seconds, and mouse's nose almost reaches tail; 4, severe curling progressing into barreling and loss of walking or righting reflex; 5, comatose or moribund. Behavioral scores were averaged within treatment groups for statistical analysis.…”

Section: Cerebral Ischemia Produced By Mcaomentioning

confidence: 99%

Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor

Weaver

Tarze²,

Moffat³

et al. 2005

J. Clin. Invest.

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Inhibitors of HIV protease have been shown to have antiapoptotic effects in vitro, yet whether these effects are seen in vivo remains controversial. In this study, we have evaluated the impact of the HIV protease inhibitor (PI) nelfinavir, boosted with ritonavir, in models of nonviral disease associated with excessive apoptosis. In mice with Fas-induced fatal hepatitis, Staphylococcal enterotoxin B-induced shock, and middle cerebral artery occlusion-induced stroke, we demonstrate that PIs significantly reduce apoptosis and improve histology, function, and/or behavioral recovery in each of these models. Further, we demonstrate that both in vitro and in vivo, PIs block apoptosis through the preservation of mitochondrial integrity and that in vitro PIs act to prevent pore function of the adenine nucleotide translocator (ANT) subunit of the mitochondrial permeability transition pore complex.

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Section: Cerebral Ischemia Produced By Mcaomentioning

confidence: 99%

Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor

Weaver

Tarze²,

Moffat³

et al. 2005

J. Clin. Invest.

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“…TTC is reduced to a redformazon product in normal brain tissue due to the presence of active mitochondrial enzymes, and has been shown to correlate to other common histological markers of brain injury [3,23]. This model of in vivo transient MCAo has been widely used as an experimental model of ischemic brain injury and has proven to be highly sensitive to various neuroprotective drug interventions [7,13,19,25,31,36,40]. In this study, postinjury treatment with RSI00642 dose-dependently reduced brain infarct volume, increased recovery in EEG power over the injured cortex and showed improvement of neurological recovery as evaluated 24 h post-injury.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Sodium Channels in Neurodegeneration and Neuroprotection

Tortella¹

2003

PsycEXTRA Dataset

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathenng and maintaining the data needed and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188), Washington, DC 20503 AGENCY USE ONLY (Leave blank)2. REPORT DATE June 2001 REPORT TYPE AND DATES COVEREDAnnual (1 Jun 00 -31 May 01) TITLE AND SUBTITLENeuronal Sodium Channels in Neurodengeration and Neuroportecion AUTHOR(S)Frank Tortella, Ph.D. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Henrv M. Jackson Foundation Rockville, Maryland 20852 E-Mail: Frank.tortella@na.amedd.army.mil The purpose of this research project is to study the role of neuronal sodium channels in mechanisms of neuronal injury, neurodegeneration and neuroprotection. The primary objective of this research project is to characterize the expression, and study the functional significance, of neuronal sodium channels during the process of injury and recovery. Also, the effects of sodium channel blockade (using antisense and channel blockers) on gene expression and neurodegeneration will be studied. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)UThe progress during our 2 nd year of this project was significant, yielding several important and critical discoveries providing a greater understanding of the injury/neurodegeneration process, and the importance of sodium gated channels in brain trauma. Three new discoveries were 1) our finding that during the brain injury process there appears to be a selective alteration in the rBI brain sodium channel with little involvement of rBIII, PNI or the PN3 channels, 2) our observations obtained from the in situ hybridization experiments that during brain injury supposedly uninjured brain tissue is indeed compromised (at least on the level of the ion channel) altered functionally as evidenced by our topographic mapping EEG studies (conducted independent of this research proposal), and 3) that sodium channel blockade with the novel drug RS100642 is highly neuroprotective and has potent therapeutic anti-seizure actions post brain trauma. We are currently developing primers for additional sodium channels and sodium-calcium exchange proteins and plan to study their expression post injury as well as complete the in situ hybridization and ASO experiments during the final year of this project. SUBJECT TERMS INTRODUCTIONSevere disruptions in ionic dynamics of the depolarizing neuron have long been recognized as possible mediators of excitotoxicity. In neurodegeneration leading to neuronal cell death, injury-induced imbalances in intracellular...

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“…Impaired synaptic transmission was persistent 24 h after reperfusion following 1 h of ischemia (39), and transient occlusion of the middle cerebral artery blocked synaptic transmission 24 h after recirculation in neurons that survived ischemia (40). In another study, correlation between the infarct volume and functional deficit was observed after 2 days, although no relation was found in the early stage of reperfusion (41). These reports show that neurologic deficits last long after ischemic events even when morphologic damage is not marked.…”

Section: Platelets (×10 4 /μL)mentioning

confidence: 91%

Alleviation of Ischemia-Induced Brain Edema by Activation of the Central Histaminergic System in Rats

Irisawa

Adachi²,

Liu

et al. 2008

J Pharmacol Sci

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Abstract. We have reported that facilitation of central histaminergic activity prevents the development of ischemia-induced brain injury. Since cerebral edema is a major cause of brain damage, we studied effects on brain edema of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H 3 -receptor antagonist, both of which enhance central histaminergic activity. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery in rats, and the water content and infarct size were determined 24 h after reperfusion. Changes in the extracellular concentration of histamine were examined in the striatum by a microdialysis procedure, and effects of these compounds were evaluated. Repeated administration of L-histidine (1000 mg / kg × 2, i.p.), immediately and 6 h after reperfusion, reduced the increase in the water contents in ischemic regions. Simultaneous administration of thioperamide (5 mg / kg, s.c.) with L-histidine (1000 mg/ kg, i.p.) completely prevented edema formation and alleviated brain infarction, although a single dose of L-histidine, immediately after reperfusion, showed no benefits. The striatal histamine level was gradually increased after reperfusion as well as during ischemia. Simultaneous administration of thioperamide with L-histidine markedly increased the brain histamine concentration, and the value increased up to 230% of that in the saline group 5 -6 h after reperfusion. L-Histidine alone did not affect the increase in the histamine output after ischemia. These findings suggest that further activation of the central histaminergic system after initiation of cerebral ischemia prevents development of ischemia-induced brain edema.

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Neurological impairment in rats after transient middle cerebral artery occlusion: a comparative study under various treatment paradigms

Cited by 201 publications

References 59 publications

Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor

Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor

Neuronal Sodium Channels in Neurodegeneration and Neuroprotection

Alleviation of Ischemia-Induced Brain Edema by Activation of the Central Histaminergic System in Rats

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