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Ischemic brain stroke is a leading cause of disability and includes hearing loss. Clinical reports have also suggested that there is hearing loss in stroke patients but the mechanism was not determined. Therefore, we hypothesized that hearing loss after cerebral ischemia may be associated with changes to the synapse, gap junction, and sodium channel (NaC) proteins. Ischemia-reperfusion injury was induced in wild-type mice (I/R group). The lesion volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining of the brain sections. BBB disruption was confirmed by Evans blue staining and leakage of bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC). We found that brain edema, infarct size, and permeability were increased in ischemic mice as compared with the sham-operated group. Caspase-3, caspase-9, and TUNEL-positive cells were increased in I/R mice, indicating neuronal apoptosis. Moreover, there were increased expressions of matrix metalloprotease's (MMP-2, -3, -9, and -13), interleukin (IL)-6, and decreased expressions of tight junction proteins (TJP) in the I/R group, as compared with the sham group, which signifies inflammation and BBB disruption. We also observed decreased levels of post-synaptic density protein-95 (PSD-95), synapse-associated protein 97 (SAP-97), connexin-43, NaC-α, and NaC-β, and increased expression of connexin-45, whereas no substantial change was observed in connexin-26 expression in the I/R group. Interestingly, auditory response was reduced in the I/R mice, indicating hearing loss. These data suggest that hearing loss in ischemic mice was primarily due to alterations in connexin, synapses, and NaC channels. Key words: cerebral ischemia, blood-brain barrier, apoptosis, hearing loss, neurotransmission. L'AVC ischemique est une des principales causes d'invalidite, dont, entre autres, la perte auditive. Les rapports cliniques laissent aussi penser que le mecanisme a l'origine de la perte auditive chez les patients ayant subi un AVC reste a clarifier. Par consequent, nous formulons l'hypothese selon laquelle la perte auditive apres une ischemie cerebrale pourrait etre associee a une alteration des proteines des synapses, des jonctions gap et des canaux sodiques. Une lesion d'ischemie-reperfusion a ete realisee chez des souris de type sauvage. Le volume des lesions a ete determine par des colorations au TTC appliquees a des coupes de cerveau. La rupture de la barriere hemo-encephalique a ete confirmee a l'aide de bleu d'Evans et des fuites de BSA-FITC. Nous avons observe que l'redeme cerebral, la taille de l'infarctus et la permeabilite augmentaient plus chez les souris ischemiques que chez celles qui avaient subi une intervention factice. Le nombre de cellules presentant de la caspase-3, caspase-9 et pour lesquelles le test de TUNEL donnait un resultat positif augmentait chez les souris soumises a l'ischemie-reperfusion, ce qui indique la presence d'une apoptose neuronale. En outre, l'augmentation de l'expression des metalloproteases matricielles (MMP-2, -3, -9 et -13) et de l'interleukine (IL)-6, et la diminution de l'expression des proteines de jonctions serrees chez les souris soumises a l'ischemie-reperfusion par rapport aux souris soumises a une intervention factice indiquaient la presence d'inflammation et d'une rupture de la barriere hemo-encephalique. Nous avons aussi observe une diminution des taux de PSD-95, de SAP-97, de connexine-43 et des sous-unites α et β des canaux sodiques, ainsi qu'une augmentation de l'expression de la connexine-45, alors qu'aucun changement substantiel n'a ete observe dans l'expression de la connexine-26 chez les souris soumises a l'ischemie-reperfusion. Il est interessant de noter que la reponse auditive etait reduite chez les souris soumises ti l'ischemie-reperfusion, ce qui indique la presence d'une perte auditive. Ces donnees laissent penser que la perte auditive observee chez les souris soumises a une ischemie etait principalement le fait d'une alteration de la connexine, des synapses et des canaux sodiques. [Traduit par la Redaction] Mots-cles: ischemie cerebrale, barriere hemo-encephalique, apoptose, perte auditive, neurotransmission., Introduction Hearing impairment, the most common sensory disability worldwide, has a profound effect on one's ability to function at a personal, social, and occupational level. Many different conditions cause hearing [...]

Problem statement: Stroke or cerebral ischemia has been recognized as one important problem worldwide. To date, the effectiveness of protective and therapeutic strategies against stroke is still very limited. Therefore, the development of novel strategy is required. Porcine brain is traditional believed to improve brain functions. Recent studies showed that the extract of porcine brain could protect against brain damage related to the oxidative stress, therefore, we hypothesized that it could protect against brain damage in stroke. Approach: To test the potential of porcine brain extract as the novel protective supplement against stroke, various doses of porcine brain extract at doses of 0.5 and 2.5 mg [kg.sup.-1] b.w. were orally given to male Wistar rats, weighing 300-350 g, at the period of 14 days before and 21 days after the occlusion of right middle cerebral artery. Then, all rats were determined the neurological score, motor performance, cognitive function and brain infarct volume. Moreover, the possible neuroprotective mechanisms of the extract were also determined via the alteration of Malondialdehyde (MDA) or lipid peroxidation product and via the activities of scavenger enzymes including Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxides (GPx). Results: The results showed that the low dose of porcine extract decreased the infarct volume and improved brain functions including neurological score, motor performance and memory deficit. In addition, it also decreased MDA but increased the activities of SOD, CAT and GPx. Conclusion: Our results suggested the potential role of porcine brain extract as neuroprotectant. The possible underlying mechanism appeared to be related to the enhanced activities of SOD, CAT and GPx which in turn resulted in the decrease MDA. Moreover, our findings may shed light on the pharmacologic basis for the clinical application of traditional Chinese medicine to protect against stroke. Key words: Porcine brain extract, cerebral ischemia, stroke, INTRODUCTION Cerebral ischemia or stroke has been recognized as one of the leading causes of death and disability in many countries (1) including in Thailand (2) due to the interruption [...]

Recently, kidney fibrosis following transplantation has become recognized as a main contributor of chronic allograft nephropathy. In transplantation, transient ischemia is an inescapable event. Reactive oxygen species (ROS) play a critical role in ischemia and reperfusion (I/R)-induced acute kidney injury, as well as progression of fibrosis in various diseases such as hypertension, diabetes, and ureteral obstruction. However, a role of ROS/ oxidative stress in chronic kidney fibrosis following I/R injury remains to be defined. In this study, we investigated the involvement of ROS/oxidative stress in kidney fibrosis following kidney I/R in mice. Mice were subjected to 30 min of bilateral kidney ischemia followed by reperfusion on day 0 and then administered with either manganese (III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, 5 mg/kg body wt ip), a cell permeable superoxide dismutase (SOD) mimetic, or 0.9% saline (vehicle) beginning at 48 h after I/R for 14 days. I/R significantly increased interstitial extension, collagen deposition, apoptosis of tubular epithelial cells, nitrotyrosine expression, hydrogen peroxide production, and lipid peroxidation and decreased copper-zinc SOD, manganese SOD, and glucose 6-phosphate dehydrogenase activities in the kidneys 16 days after the procedure. MnTMPyP administration minimized these postischemic changes. In addition, MnTMPyP administration significantly attenuated the increases of [alpha]-smooth muscle actin, PCNA, S100A4, CD68, and heat shock protein 47 expression following I/R. We concluded that kidney fibrosis develops chronically following I/R injury, and this process is associated with the increase of ROS/ oxidative stress. interstitial fibrosis; ischemia-reperfusion; superoxide; s-smooth muscle actin; manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin

Secretoneurin (SN), a neuropeptide derived from secretogranin II, promotes neurite outgrowth of immature cerebellar granule cells. SN also aids in the growth and repair of neuronal tissue, although the precise mechanisms underlying the promotion of brain tissue neuroprotection and plasticity by SN are not understood. Here, in a rat model of stroke and in ischemic human brain tissue, SN was markedly upregulated in both neurons and endothelial cells. SN-mediated neuroprotection rescued primary cortical cell cultures from oxygen/glucose deprivation. SN also induced expression of the antiapoptotic proteins Bcl-2 and Bcl-xL through the Jak2/Stat3 pathway and inhibited apoptosis by blocking caspase-3 activation. In addition, rats with occluded right middle cerebral arteries showed less cerebral infarction, improved motor performance, and increased brain metabolic activity following i.v. administration of SN. Furthermore, SN injection enhanced stem cell targeting to the injured brain in mice and promoted the formation of new blood vessels to increase local cortical blood flow in the ischemic hemisphere. Both in vitro and in vivo, SN not only promoted neuroprotection, but also enhanced neurogenesis and angiogenesis. Our results demonstrate that SN acts directly on neurons after hypoxia and ischemic insult to further their survival by activating the Jak2/Stat3 pathway., Introduction Secretoneurin (SN) is a 33-amino acid neuropeptide produced by endoproteolytic processing of chromogranin/secretogranin family proteins, which are found in large dense-core vesicles in a wide variety of cell types [...]

Byline: Tobias Back (2), Thomas Hemmen (2), Olaf G. Schuler (1) Keywords: brain ischemia; MRI; cardiac arrest; stroke; pathophysiology; cerebral ischemia Abstract: Abstract. There is sound evidence from histopathological and magnetic resonance imaging (MRI) studies that focal ischemic brain lesions tend to increase in size over time. Considerable lesion growth was observed in models of animal stroke as well as in patients presenting with hemispheric stroke. In focal cerebral ischemia, lesions predominantly enlarge early within 12 hours after onset. Ischemic injury is caused by complete necrosis in most of the affected tissue. By contrast, in global cerebral ischemia as seen after cardiac arrest, lesions appear late (&gt 12 h) in selectively vulnerable brain regions such as the hippocampus, and neurons are damaged by apoptotic cell death. The high and regionally distinct vulnerability of the brain explains why prolonged periods of global ischemia result in widespread loss of energy metabolites combined with diffuse brain edema and global damage. Postulated mechanisms involved in lesion growth include among others excitotoxicity, periinfarct depolarizations, lactacidosis, microcirculatory disturbances, and flow-metabolism uncoupling. Research in the field faces two main challenges. First,maturation phenomena of injury may require special imaging techniques to detect early ischemic changes. Second, the dynamic nature of the changes underlines the need to conduct longitudinal studies with a variety of imaging techniques (e. g., metabolic imaging, diffusion/perfusion MRI, positron emission tomography) that require a differentiated interpretation of the alterations observed. Author Affiliation: (1) Department of Neurology, Ludwig Maximilians University Munich, Marchioninistrasse 15, 81377, Munchen, Germany (2) Department of Neurology, Philipps University Marburg, R.-Bultmann-Str. 8, 35039, Marburg, Germany Article History: Registration Date: 01/01/2004 Received Date: 04/08/2003 Accepted Date: 15/01/2004

Byline: Floor C. Bakker (1), Catharina J. M. Klijn (2), Aagje Jennekens-Schinkel (1), Ingeborg Tweel (4), Cornelis A. F. Tulleken (3), L. Jaap Kappelle (2) Keywords: cognition disorders; carotid artery disease; transient ischemic attack Abstract: Abstract. Although transient ischemic attacks (TIAs) by definition do not cause lasting neurological deficits, cognitive impairment has been suggested in patients with carotid artery disease who have suffered from a TIA. The purpose of our study was to assess whether patients with carotid artery disease and TIAs are cognitively impaired, to describe the frequency, nature and severity of this impairment, and to search for associated patient characteristics. Thirty-nine consecutive patients with carotid occlusion and ipsilateral cerebral or retinal TIAs, and 46 healthy controls underwent extensive neuropsychological assessment. Performances were compared group-wise with analysis of variance. In addition, the presence of cognitive impairment in the individual patient was determined. Associations between illness characteristics and cognitive impairment were explored with regression analysis. Fifty-four percent of patients were cognitively impaired. Cognitive deficits were non-specific in nature and mild in severity. Impairment occurred also in patients with isolated retinal symptoms and in those without visible ischemic brain lesions on MRI. Neither the presence of any vascular risk factor, the side of the symptomatic carotid occlusion, the uni- or bilaterality of carotid occlusion, nor the number of cerebral ischemic lesions were predictors of cognitive impairment. We conclude that about half of the patients with carotid artery occlusion and ipsilateral TIAs are cognitively impaired. The presence of cognitive deficits in patients with isolated retinal symptoms and in those without cerebral ischemic lesions on MRI argues against an exclusive role for structural brain damage in the pathogenesis of these deficits. Author Affiliation: (1) Dept. of Neurology Sector of Neuropsychology KG 01.327.1, University Medical Center Utrecht, 85090, 3508 AB, Utrecht, The Netherlands (2) University Dept. of Neurology, University Medical Center Utrecht and the Rudolf Magnus Institute of Neurosciences, Utrecht, The Netherlands (3) University Dept. of Neurosurgery, University Medical Center Utrecht and the Rudolf Magnus Institute of Neurosciences, Utrecht, The Netherlands (4) University Center for Biostatistics, University Medical Center Utrecht and the Rudolf Magnus Institute of Neurosciences, Utrecht, The Netherlands Article History: Registration Date: 01/01/2003 Received Date: 22/05/2002 Accepted Date: 07/07/2003

Byline: K. Santhosh, E. Jaydadevan, T. Kapilamoorthy, P. Sylaja Sir, Recanalization of occluded internal carotid artery (ICA) via hypertrophied vasa vasorum is a rare well-recognized phenomenon, described in atherosclerotic arterial [...]

* Anomalous origin of 4 separate coronary ostia from a single coronary sinus has rarely been reported. We report what is to our knowledge a previously undescribed variation characterized by the left anterior descending, left ramus, left circumflex, and right coronary arteries originating from separate ostia in the right sinus of Valsalva. In addition, the autopsy disclosed features of hypertrophic cardiomyopathy, rarely associated with congenital coronary anomalies. (Arch Pathol Lab Med. 2001;125:1489-1490), REPORT OF A CASE A 49-year-old, 222-lb black man underwent cervical-spinal fusion. His preoperative evaluation was unremarkable, with the exception of nonspecific electrocardiographic changes that prompted an echocardiogram, which was [...]

The ankle brachial index, a test that measures blood flow in the ankle, can identify peripheral artery disease (PAD)--and thus the risk of future cardiovascular events--in people who survive strokes [...]