Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to pharmacologically investigate the possible role of nuclear factor kappa B (NF-kappaB) in the reversal of global cerebral injury induced by ischemia and reperfusion after ischemic postconditioning. Bilateral carotid artery occlusion for 17 min followed by reperfusion for 24 h was employed to produce ischemia- and reperfusion-induced cerebral injury in mice. Cerebral infarct size was measured by using triphenyltetrazolium chloride staining. Memory was evaluated using the Morris water maze test. The rotarod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced a marked increase in cerebral infarct size, impairment of memory, and motor coordination. A set of 5 episodes of carotid artery occlusion for a period of 10 s and reperfusion of 10 s (ischemic postconditioning) significantly prevented ischemia-reperfusion-induced cerebral infarct size and behavioral deficits measured in terms of loss of memory and motor coordination. Diethyl dithiocarbamic acid sodium salt trihydrate (DDA) (100 mg/kg, i.p.), an inhibitor of NF-kappaB, given 30 min before ischemia attenuated the beneficial effects of ischemic postconditioning. It may be concluded that the beneficial effects of ischemic postconditioning on global cerebral ischemia- and reperfusion-induced cerebral injury and behavioral deficits may involve activation of the NF-kappaB-linked pathway.
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PMID:Diethyl dithiocarbamic acid, a possible nuclear factor kappa B inhibitor, attenuates ischemic postconditioning-induced attenuation of cerebral ischemia-reperfusion injury in mice. 1914 17

Nitroxyl (HNO) donor compounds function as potent vasorelaxants, improve myocardial contractility and reduce ischemia-reperfusion injury in the cardiovascular system. With respect to the nervous system, HNO donors have been shown to attenuate NMDA receptor activity and neuronal injury, suggesting that its production may be protective against cerebral ischemic damage. Hence, we studied the effect of the classical HNO-donor, Angeli's salt (AS), on a cerebral ischemia/reperfusion injury in a mouse model of experimental stroke and on related in vitro paradigms of neurotoxicity. I.p. injection of AS (40 mumol/kg) in mice prior to middle cerebral artery occlusion exacerbated cortical infarct size and worsened the persistent neurological deficit. AS not only decreased systolic blood pressure, but also induced systemic oxidative stress in vivo indicated by increased isoprostane levels in urine and serum. In vitro, neuronal damage induced by oxygen-glucose-deprivation of mature neuronal cultures was exacerbated by AS, although there was no direct effect on glutamate excitotoxicity. Finally, AS exacerbated oxidative glutamate toxicity - that is, cell death propagated via oxidative stress in immature neurons devoid of ionotropic glutamate receptors. Taken together, our data indicate that HNO might worsen cerebral ischemia-reperfusion injury by increasing oxidative stress and decreasing brain perfusion at concentrations shown to be cardioprotective in vivo.
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PMID:Nitroxyl exacerbates ischemic cerebral injury and oxidative neurotoxicity. 1961 35

Tissue kallikrein (KLK1) processes low-molecular weight kininogen to produce vasoactive kinins, which exert biological functions via kinin receptor signaling. Using various delivery approaches, we have demonstrated that tissue kallikrein through kinin B2 receptor signaling exhibits a wide spectrum of beneficial effects by reducing cardiac and renal injuries, restenosis and ischemic stroke, and by promoting angiogenesis and skin wound healing, independent of blood pressure reduction. Protection by tissue kallikrein in oxidative organ damage is attributed to the inhibition of apoptosis, inflammation, hypertrophy and fibrosis. Tissue kallikrein also enhances neovascularization in ischemic heart and limb. Moreover, tissue kallikrein/kinin infusion not only prevents but also reverses kidney injury, inflammation and fibrosis in salt-induced hypertensive rats. Furthermore, there is a wide time window for kallikrein administration in protection against ischemic brain infarction, as delayed kallikrein infusion for 24 h after cerebral ischemia in rats is effective in reducing neurological deficits, infarct size, apoptosis and inflammation. Importantly, in the clinical setting, human tissue kallikrein has been proven to be effective in the treatment of patients with acute brain infarction when injected within 48 h after stroke onset. Finally, kallikrein promotes skin wound healing and keratinocyte migration by direct activation of protease-activated receptor 1.
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PMID:Tissue kallikrein in cardiovascular, cerebrovascular and renal diseases and skin wound healing. 2018 Jun 44

Androgens within physiological ranges protect castrated male mice from cerebral ischemic injury. Yet, underlying mechanisms are unclear. Here, we report that, after middle cerebral artery occlusion (MCAO), salt-induced kinase 1 (SIK1) was induced by a potent androgen-dihydrotestosterone (DHT) at protective doses. To investigate whether SIK1 contributes to DHT neuroprotection after cerebral ischemia, we constructed lentivirus-expressing small interference RNA (siRNA) against SIK1. The SIK1 knockdown by siRNA exacerbated oxygen-glucose deprivation (OGD)-induced cell death in primary cortical neurons, suggesting that SIK1 is an endogenous neuroprotective gene against cerebral ischemia. Furthermore, lentivirus-mediated SIK1 knockdown increased both cortical and striatal infarct sizes in castrated mice treated with a protective dose of DHT. Earlier studies show that SIK1 inhibits histone deacetylase (HDAC) activities by acting as a class IIa HDAC kinase. We observed that SIK1 knockdown decreased histone H3 acetylation in primary neurons. The SIK1 siRNA also exacerbated OGD-induced neuronal death in the presence of trichostatin A (TSA), an HDAC inhibitor, and decreased histone H3 acetylation at 4 hours reoxygenation in TSA-treated neurons. Finally, we showed that DHT at protective doses prevented ischemia-induced histone deacetylation after MCAO. Our finding suggests that SIK1 contributes to neuroprotection by androgens within physiological ranges by inhibiting histone deacetylation.
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PMID:Role of salt-induced kinase 1 in androgen neuroprotection against cerebral ischemia. 2058 19

This study was conducted to demonstrate ultra-low-molecular-weight heparin's neuroprotective effects on ischemic injury both in vivo and in vitro studies. In vitro, the effect of ultra-low-molecular-weight heparin was tested in cultured PC12 cells exposed to Earle's solution containing sodium dithionite, to identify its neuroprotection to PC12 cells damaged by oxygen-glucose deprivation (OGD). The cell injury was detected by the tetrazolium salt 3-(4,5-dimethyl-2-thiazolyl)-2,5 diphenyl-2H tetrazolium bromide (MTT) assay. In vivo, male Wistar rats with middle cerebral artery occlusion were evaluated for infarct volume followed by the treatment with ultra-low-molecular-weight heparin. The results in vitro showed that ultra-low-molecular-weight heparin significantly inhibited PC12 cells damage induced by OGD. Results in vivo showed that vein injection of Ultra-Low-molecular-weight heparin at doses of 0.5 and 1.0 mg/kg exerted significant neuroprotective effects on rats with focal cerebral ischemic injury by significantly reducing the infarct volume compared with the injury group. All the findings suggest that ultra-low-molecular-weight heparin might act as a neuroprotective agent useful in the treatment of cerebral ischemia.
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PMID:Neuroprotective effects of ultra-low-molecular-weight heparin in vitro and vivo models of ischemic injury. 2060 97

Cerebral salt wasting (CSW) frequently occurs concomitantly with subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, reduces total blood volume, aggravates cerebral vasospasm and causes cerebral ischemia after SAH. This study examined the inhibitory effect of hydrocortisone on CSW in rat SAH models. Hydrocortisone had an inhibitory effect on CSW because hydrocortisone functioned in a dose-dependent manner to inhibit the increase in sodium excretion and sodium/potassium ratio after SAH onset. We conclude that hydrocortisone is a useful drug for the treatment of CSW after SAH.
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PMID:Inhibitory effect of hydrocortisone on cerebral salt wasting after subarachnoid hemorrhage in rats. 2122 8

The kidney and the brain play a major role in maintaining normal homeostasis of the extracellular fluid by neuroendocrine regulation of sodium and water balance. Therefore, disturbances of sodium balance are common in patients with central nervous system (CNS) disorders and clinicians should focus not only on the CNS lesion, but also on the potentially deleterious complications. Hyponatremia is the most common and important electrolyte disorder affecting patients with critical neurologic diseases. In these patients, the maladaptation to hyponatremia by impaired osmoregulation in pathologic lesions of brain may cause more aggressive cerebral edema and increased intracranial pressure due to hypoosmolality induced by hyponatremia. Furthermore, hyponatremia accompanied by CNS disorders has shown to increase delayed cerebral ischemia and mortality rates. Two main pathophysiologies of hyponatremia, excluding iatrogenic causes, are inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt wasting (CSW) syndrome. Differential diagnosis between these two entities can be difficult due to considerable overlap in the laboratory findings and clinical situations. SIADH is in a volume expanded status due to inappropriately secreted arginine vasopressin (AVP) and requires water restriction. However, CSW syndrome is characterized by renal sodium wasting mainly due to increased natriuretic peptides resulting in volume depletion and follows appropriate secretion of AVP. Therefore, maintenance of volume status and sodium replacement is the mainstay of treatment in CSW syndrome. In this review, we aimed to describe the regulation of sodium and water balance, and pathophysiology, diagnosis and treatment of hyponatremia in neurologic patients, especially focusing on SIADH and CSW syndrome.
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PMID:Hyponatremia in patients with neurologic disorders. 2146 86

A simple and solvent-minimized sample preparation technique based on two-phase hollow fiber liquid phase microextraction has been developed and used to quantify the osthole in cerebral ischemia reperfusion rat plasma following oral administration. The analysis was performed by reversed phase high performance liquid chromatography with fluorescence detection. Extraction conditions such as solvent identity, agitation rate, salt concentration, extraction time, and length of the hollow fiber were optimized. Under the optimized conditions, the linear range of osthole in rat plasma was 5-500 ng mL(-1) (r(2) = 0.9997). The limit of detection (LOD) was 2 ng mL(-1) (S/N = 3) with limit of quantification (LOQ) being 5 ng mL(-1). The validated method has been successfully applied for pharmacokinetic studies of osthole from cerebral ischemia reperfusion rat plasma after oral administration.
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PMID:Application of hollow fiber liquid phase microextraction coupled with high-performance liquid chromatography for the study of the osthole pharmacokinetics in cerebral ischemia hypoperfusion rat plasma. 2173 62

Sodium and fluid management in the brain injured patient directly impacts cerebral edema and cerebral perfusion pressure. Sodium is a major determinant of neuronal size and therefore hyponatremia is aggressively avoided, as hypoosmolar states result in cerebral edema. Negative fluid balance is often avoided because resultant drop in cerebral perfusion pressure can contribute to cerebral ischemia, further inducing secondary neuronal injury. Patients with brain injury are at risk for disorders of sodium and fluid balance (eg, syndrome of inappropriate antidiuresis, cerebral salt wasting, and diabetes insipidus). Knowledge of normal homeostatic and brain regulatory volume mechanisms is necessary to avoid inducing further neuronal or systemic injury while trying to correct sodium and fluid disorders in brain injured patients. Osmotherapy is a common part of managing cerebral edema in neurocritical care units, but more studies are needed to establish practice guidelines.
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PMID:Sodium and fluid management in acute brain injury. 2262 7

Nicotine has been reported to exert certain protective effect in the Parkinson's and Alzheimer's diseases. Whether it has a similar action in focal cerebral ischemia was unclear. In the present study, rats received either an injection of (-)-nicotine hydrogen tartrate salt (1.2 mg/kg, i.p.) or the vehicle 2 h before the 120 min middle cerebral artery occlusion. Neurological deficits and histological injury were assessed at 24 h after reperfusion. The content of endocannabinoids and the expression of cannabinoid receptor CB1 in brain tissues were determined at different time points after nicotine administration. Results showed that nicotine administration ameliorated neurological deficits and reduced infarct volume induced by cerebral ischemia in the rats. The neuroprotective effect was partially reversed by CB1 blockage. The content of the endocannabinoids N-arachidonylethanolamine and 2-arachidonoylglycerol, as well as the expression of cannabinoid receptor CB1 were up-regulated in brain tissues after nicotine delivery. These results suggest that endogenous cannabinoid system is involved in the nicotine-induced neuroprotection against transient focal cerebral ischemia.
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PMID:Nicotine-induced neuroprotection against ischemic injury involves activation of endocannabinoid system in rats. 2319 60


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