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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was to examine the alterations in the phosphorylation of mitogen-activated protein kinase (MAPK) family in transient brain ischemia under a hyperglycemia and to highlight the molecular mechanisms by which hyperglycemia exacerbates brain damage resulting from stroke. Extracellular signal-regulated protein kinase (ERK) expression was studied in rats subjected to global brain ischemia with pre-ischemic normoglycemic (CIN) and hyperglycemic (CIH) conditions. In another group, the hyperglycemic ischemic rats were pretreated with ERK inhibitor U0126 (U0126). Increased phospho-ERK1/2 immunoreactive neurons in the cingulate cortex and hippocampal CA3 were detected in CIN after ischemia and reperfusion. The numbers of phospho-ERK1/2-positive neurons were further increased significantly in CIH compared to the CIN. Pretreatment with U0126 in CIH rats significantly decreased ERK1/2 immunoreactive cells. Western blot analyses confirmed that phospho-ERK1/2 increased significantly after 30 min ischemia and reperfusion compared to non-ischemic controls in both the CIN and CIH groups. The increase of phospho-ERK1/2 was more prominent in the CIH than in the CIN group after 3 and 6h of reperfusion. Treatment with U0126 significantly reduced phospho-ERK1/2 in the CIH group. The findings presented here suggest that ERK1/2 may play a role in mediating neuronal cells death under hyperglycemic condition.
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PMID:Hyperglycemia increased brain ischemia injury through extracellular signal-regulated protein Kinase. 1634 98

Studies involving animal models of acute central nervous system (CNS) stroke and trauma strongly indicate that sex and/or hormonal status are important determinants of outcome after brain injury. The present study was undertaken to examine the ability of estradiol to protect hippocampal neurons from lateral fluid percussion brain injury. Sprague-Dawley female rats (211-285 g; n = 119) were ovariectomized, and a subset (n = 66) were implanted with 17beta-estradiol pellets to provide near physiological levels of estradiol. Animals were subjected to lateral fluid percussion brain injury or sham injury 1 week later. Activation of caspase-3 (n = 26) and TUNEL staining (n = 21) were assessed at 3 and 12 h after injury, respectively, in surviving control and estradiol-treated animals. Memory retention was examined using a Morris water maze test in a separate subset of animals (n = 43) at 8 days after injury. Activated caspase-3 and TUNEL staining were observed in the dentate hilus, granule cell layer, and CA3 regions in all injured rats, indicative of selective hippocampal cell apoptosis in the acute posttraumatic period. Estradiol did not significantly alter the number of hippocampal neurons exhibiting caspase-3 activity or TUNEL staining. Brain injury impaired cognitive ability, assessed at 1 week post-injury (p < 0.001). However, estradiol at physiological levels did not significantly alter injury-induced loss of memory. These data indicate that estradiol at physiological levels does not ameliorate trauma-induced hippocampal injury or cognitive deficits in ovariectomized female rats.
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PMID:Effects of estradiol on cognition and hippocampal pathology after lateral fluid percussion brain injury in female rats. 1718 91

Transient forebrain ischemia induces delayed, selective neuronal death in the CA1 region of the hippocampus. The underlying molecular mechanisms are as yet unclear, but it is known that activation of L-type Ca2+ channels specifically increases the expression of a group of genes required for neuronal survival. Accordingly, we examined temporal changes in L-type calcium-channel activity in CA1 and CA3 pyramidal neurons of rat hippocampus after transient forebrain ischemia by patch-clamp techniques. In vulnerable CA1 neurons, L-type Ca2+-channel activity was persistently downregulated after ischemic insult, whereas in invulnerable CA3 neurons, no change occurred. Downregulation of L-type calcium channels was partially caused by oxidation modulation in postischemic channels. Furthermore, L-type but neither N-type nor P/Q-type Ca2+-channel antagonists alone significantly inhibited the survival of cultured hippocampal neurons. In contrast, specific L-type calcium-channel agonist remarkably reduced neuronal cell death and restored the inhibited channels induced by nitric oxide donor. More importantly, L-type calcium-channel agonist applied after reoxygenation or reperfusion significantly decreased neuronal injury in in vitro oxygen-glucose deprivation ischemic model and in animals subjected to forebrain ischemia-reperfusion. Together, the present results suggest that ischemia-induced inhibition of L-type calcium currents may give rise to delayed death of neurons in the CA1 region, possibly via oxidation mechanisms. Our findings may lead to a new perspective on neuronal death after ischemic insult and suggest that a novel therapeutic approach, activation of L-type calcium channels, could be tested at late stages of reperfusion for stroke treatment.
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PMID:Contribution of downregulation of L-type calcium currents to delayed neuronal death in rat hippocampus after global cerebral ischemia and reperfusion. 1749 11

Inflammation and neurodegeneration coexist in many acute damage and chronic CNS disorders (e.g., stroke, Alzheimer's disease, Parkinson's disease). A well characterized animal model of brain damage involves administration of kainic acid, which causes limbic seizure activity and subsequent neuronal death, especially in the CA1 and CA3 pyramidal cells and interneurons in the hilus of the hippocampus. Our previous work demonstrated a potent anti-inflammatory and neuroprotective effect of two thiadiazolidinones compounds, NP00111 (2,4-dibenzyl-[1,2,4]thiadiazolidine-3,5-dione) and NP01138 (2-ethyl-4-phenyl-[1,2,4]thiadiazolidine-3,5-dione), in primary cultures of cortical neurons, astrocytes, and microglia. Here, we show that injection of NP031112, a more potent thiadiazolidinone derivative, into the rat hippocampus dramatically reduces kainic acid-induced inflammation, as measured by edema formation using T2-weighted magnetic resonance imaging and glial activation and has a neuroprotective effect in the damaged areas of the hippocampus. Last, NP031112-induced neuroprotection, both in vitro and in vivo, was substantially attenuated by cotreatment with GW9662 (2-chloro-5-nitrobenzanilide), a known antagonist of the nuclear receptor peroxisome proliferator-activated receptor gamma, suggesting that the effects of NP031112 can be mediated through activation of this receptor. As such, these findings identify NP031112 as a potential therapeutic agent for the treatment of neurodegenerative disorders.
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PMID:NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders. 1752 20

The role of the hippocampus in associative memory is the establishment of long-term, declarative memories. For example, memories for facts, name and life experiences. Damage to the hippocampus leads to loss of ability to convert short-term memory to new long-term memories. This can happen due to epilepsy, stroke, dementia or head injuries. One of the possibilities of providing a solution to this problem is by prosthesis. The first step towards this is building of biomimetic model of the region. A system modeling approach is used to build the biomimetic model of the CA3 by the use of biological repetitive firing neurons of R.J.Macgregor. The output of the neuron model is a spiking output so there is no need for a separate spike producing circuitry. The electronic model is also presented with a possible circuit for realization of the plasticity. The weights of the network are updated by the synaptic activity plasticity rule (SAPR), which has weight updation depending on the value of the post synaptic potential of the spiking neurons. The various paths of the flow of information in and out of the hippocampus and the possible connections for the prosthesis are presented. The project takes into consideration the various experimental finding and the advances in synaptic plasticity published so far for building this biomimetic model.
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PMID:A Spiking neural network of the CA3 of the hippocampus can be a neural prosthesis for lost cognitive functions. 1800 68

Ascorbic acid (AA) and dehydroascorbic acid (DHA) have been shown to have protective effects as anti-oxidants in experimental neurological disorder models such as stroke, ischemia, and epileptic seizures. The present study was conducted to examine the protective effects of AA and DHA on kainic acid (KA) neurotoxicity using organotypic hippocampal slice cultures. After 12h KA treatment, significant delayed neuronal death was detected in the CA3, but not the CA1, region. Pretreatment with intermediate doses of AA and DHA significantly prevented cell death and inhibited reactive oxygen species (ROS) level, and mitochondrial dysfunction in the CA3 region. In contrast, pretreatment with low or high doses of AA or DHA was not effective. These data suggest that pretreatment with both AA and DHA has dose-dependent neuroprotective effects on KA-induced neuronal injury through inhibiting ROS generation and mitochondrial dysfunction.
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PMID:Anti-oxidant effect of ascorbic and dehydroascorbic acids in hippocampal slice culture. 1803 37

Endoplasmic reticulum (ER) stress, which is caused by an accumulation of unfolded proteins in the ER lumen, is associated with stroke and with neurodegenerative diseases such as Parkinson's and Alzheimer diseases. We assessed the expression patterns of immunoglobulin heavy chain binding protein (BiP)/glucose-regulated protein (GRP) 78 (an ER-resident molecular chaperone whose expression serves as a good marker of ER-stress), activating transcription factor (ATF)-4, and C/EBP homology protein (CHOP) by immunohistochemistry and/or Western blotting after transient forebrain ischemia in gerbils. Double-fluorescent staining involving CHOP immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) method was performed to clarify the involvement of CHOP in cell death. Immunohistochemical and Western blot analyses of the hippocampal Cornet d'Ammon (CA)1 subfield showed that BiP expression was increased at 12 h, peaked at 3 days, then decreased (versus the control group). A transient increase was detected in CA3 at 1 day after ischemia, but BiP expression was unchanged in dentate gyrus and cortex. Signals for ATF-4 and CHOP were increased at 1 day and 3 days in CA1, and at 12 h in CA3. Co-localization of CHOP immunoreactivity and DNA fragmentation was detected by the TUNEL method at 3 days after ischemia in CA1, but not at 12 h in CA3. These findings are consistent with ER stress playing a pivotal role in post-ischemic neuronal death in the gerbil hippocampal CA1 subfield.
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PMID:Involvement of endoplasmic reticulum stress in the neuronal death induced by transient forebrain ischemia in gerbil. 1808 69

The effects of thrombin, a blood coagulation serine protease, were studied in rat hippocampal slices, in an attempt to comprehend its devastating effects when released into the brain after stroke and head trauma. Thrombin acting through its receptor, protease-activated receptor 1 (PAR1), produced a long-lasting enhancement of the reactivity of CA1 neurons to afferent stimulation, an effect that saturated the ability of the tissue to undergo tetanus-induced long-term potentiation. This effect was mediated by activation of a PAR1 receptor, because it was shared by a PAR1 agonist, and was blocked by its selective antagonist. An independent effect of thrombin involved the lowering of the threshold for generating epileptic seizures in CA3 region of the hippocampus. Thus, the experiments in a slice mimicked epileptic and cognitive dysfunction induced by thrombin in the brain, and suggest that these effects are mediated by activation of the PAR1 receptor.
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PMID:Thrombin induces long-term potentiation of reactivity to afferent stimulation and facilitates epileptic seizures in rat hippocampal slices: toward understanding the functional consequences of cerebrovascular insults. 1819 72

Transient global ischemia induces delayed neuronal death in certain cell types and brain regions while sparing cells in other areas. A key process through which oxygen-glucose deprivation triggers cell death is the excessive accumulation of the neurotransmitter glutamate leading to over excitation of neurons. In certain neurons this increase in glutamate will potentiate the NMDA type of glutamate receptor, which can then initiate cell death. This review provides an update of the neurophysiological, cellular and molecular mechanisms inducing post-ischemic plasticity of NMDA receptors, focusing on the sensitive CA1 pyramidal neurons in the hippocampus as compared to the relatively resistant neighboring CA3 neurons. Both a change in the equilibrium between protein tyrosine kinases/phosphatases and an increased density of surface NMDA receptors in response to ischemia may explain the selective vulnerability of specific cell types. Implications for the treatment of stroke and reasons for the failures of human clinical trials utilizing NMDA receptor antagonists are also discussed.
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PMID:[Transient brain ischemia: NMDA receptor modulation and delayed neuronal death]. 1827 81

Stroke is a common cause of death and severe disability among adults in developed countries. Cigarette smoking adversely affects human health in many ways and is considered to be a risk factor for a stroke. However, the mechanism that determines the relative importance of neurotrophins in this process remains unclear. To study the effect of chronic cigarette smoking on ischemic stroke, in situ hybridization and immunohistochemistry were employed to detect the mRNA and protein expression of neurotrophin-3 (NT-3), respectively, which is thought to play a critical role in protection against neuronal death in brain ischemia. Rats, with or without chronic cigarette smoking, were subjected to 20 min of transient forebrain ischemia. Distribution and quantification of mRNA and protein of NT-3 in the whole hippocampus and the cell death in the hippocampal CA1-CA3 regions were determined in these rats. Experimental results show that chronic cigarette smoking produces a significantly delay and persistent down-regulation of ischemia-induced NT-3 mRNA and protein changes at 6-24h post-ischemia, and seemingly increases neuron death 7 days after reperfusion. These experimental results indicate that by influencing NT-3 expression, directly or indirectly, chronic cigarette smoking has a potentially harmful effect when acute brain ischemia attacks.
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PMID:Cigarette smoking decreases neurotrophin-3 expression in rat hippocampus after transient forebrain ischemia. 1828 10


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