Piracetam attenuates minoxidil-induced antinociception in mice

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Reversal of pentylenetetrazole-induced seizure activity in mice by nickel chloride

Objective: The present study was designed to investigate the anticonvulsant potential of nickel which is shown to selectively block t-type calcium channels by using nickel choride on pentylenetetrazole (80 mg/kg) induced seizure activity model in mice. Materials and Methods: Seizures were assessed in terms of onset of Straub′s tail phenomenon and onset of jerky movements of the whole body, convulsions, and death. Sodium valproate served as a standard control in the present study. Results: Nickel chloride (5 mg/kg i.p. and 10 mg/kg i.p.) attenuated pentylenetetrazole-induced seizure activity in mice, as reflected by a significant increase in the onset time of Straub′s tail phenomenon and onset of jerky movements of the whole body, convulsions, and death. High dose of nickel chloride showed more pronounced anticonvulsant action than sodium valproate. Conclusions: The anticonvulsant action of nickel chloride was noticeable in this study. However, further studies are required to elucidate its full anticonvulsant potential

Polish Academy of Sciences

Role of phosphoinositide 3-kinase in ischemic postconditioning-induced attenuation of cerebral ischemia-evoked behavioral deficits in mic

Impact of Hypoglycemia on Brain Metabolism During Diabetes

Diabetes is a metabolic disease afflicting millions of people worldwide. A substantial fraction of world's total healthcare expenditure is spent on treating diabetes. Hypoglycemia is a serious consequence of anti-diabetic drug therapy, because it induces metabolic alterations in the brain. Metabolic alterations are one of the central mechanisms mediating hypoglycemia-related functional changes in the brain. Acute, chronic, and/or recurrent hypoglycemia modulate multiple metabolic pathways, and exposure to hypoglycemia increases consumption of alternate respiratory substrates such as ketone bodies, glycogen, and monocarboxylates in the brain. The aim of this review is to discuss hypoglycemia-induced metabolic alterations in the brain in glucose counterregulation, uptake, utilization and metabolism, cellular respiration, amino acid and lipid metabolism, and the significance of other sources of energy. The present review summarizes information on hypoglycemia-induced metabolic changes in the brain of diabetic and non-diabetic subjects and the manner in which they may affect brain function

Ameliorative potential of conditioning on ischemia-reperfusion injury in diabetes

Diabetes is a serious metabolic disease characterized by hyperglycemia. Diabetes also leads to several long-term secondary complications. Cardiovascular disease is an important complication of diabetes and is a major contributor to morbidity and mortality in diabetic subjects. The discovery of conditioning-induced ischemic or anoxic tolerance has led to the demonstration of the protective potential of conditioning as a treatment strategy to mitigate ischemia-reperfusion injury. Diabetes modulates multiple metabolic pathways and signal transduction cascades. Some of these pathways may overlap with mechanisms that mediate the beneficial effects of conditioning from the body's reaction to a sublethal insult, indicating the possibility of a potential interaction between diabetes and conditioning. Studies demonstrate that diabetes abrogates the ameliorative effect of various forms of conditioning, such as ischemic preconditioning, ischemic postconditioning, remote ischemic conditioning and pharmacological conditioning, on ischemia-reperfusion injury in various animal models. Moreover, drugs used to treat diabetes may have a potential impact on protection afforded by conditioning from ischemic injury. Studies also indicate a potential impact of various anti-diabetic drugs on conditioning-induced protection. Overall, the literature suggests that a better understanding of the overlap among pathways activated by diabetes and those involved in induction of ischemia tolerance may help identify ideal conditioning paradigms to protect diabetic subjects from ischemic injury

Role of ATP-sensitive potassium channels in the piracetam induced blockade of opioid effects

1050-1054The present study has been designed to investigate the effect of piracetam on morphine/ buprenorphine-induced antinociception in rats and effect of piracetam on morphine or minoxidil induced relaxation in KCl-precontracted isolated rat aortic ring preparation. Nociceptive threshold was measured by the tail flick test in rats. The cumulative dose responses of morphine or minoxidil were recorded in KCl-precontracted isolated rat aortic ring preparation. Piracetam attenuated buprenorphine-induced antinociception in rats. Piracetam significantly reduced the morphine and minoxidil induced relaxation in KCl precontracted isolated rat aortic ring preparation suggesting that piracetam interferes with opioid receptor and ATP-sensitive potassium channel (KATP) opener mediated responses in vitro. Thus, it may be suggested that piracetam attenuates opioid effects by an opioid receptor-KATP channel linked mechanism

Remote ischaemic preconditioning and prevention of cerebral injury

247-252Bilateral carotid artery occlusion of 10 min followed by reperfusion for 24 hr was employed in present study to produce ischaemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Short-term memory was evaluated using elevated plus maze. Inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired short-term memory, motor co-ordination and lateral push response. A preceding episode of mesenteric artery occlusion for 15 min and reperfusion of 15 min (remote mesenteric ischaemic preconditioning) prevented markedly ischaemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of short-term memory, motor coordination and lateral push response. Glibenclamide (5 mg/kg, iv) a KATP channel blocker and caffeine (7 mg/kg, iv) an adenosine receptor blocker attenuated the neuroprotective effect of remote mesenteric ischaemic preconditioning. It may be concluded that neuroprotective effect of remote mesenteric ischaemic preconditioning may be due to activation of adenosine receptors and consequent activation of KATP channels in mice

Tobacco Use: A Major Risk Factor of Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (sICH) is one of the deadliest subtypes of stroke, and no treatment is currently available. One of the major risk factors is tobacco use. In this article, we review literature on how tobacco use affects the risk of sICH and also summarize the known effects of tobacco use on outcomes following sICH. Several studies demonstrate that the risk of sICH is higher in current cigarette smokers compared to non-smokers. The literature also establishes that cigarette smoking not only increases the risk of sICH but also increases hematoma growth, results in worse outcomes, and increases the risk of death from sICH. This review also discusses potential mechanisms activated by tobacco use which result in an increase in risk and severity of sICH. Exploring the underlying mechanisms may help alleviate the risk of sICH in tobacco users as well as may help better manage tobacco user sICH patients

Ischemic brain injury in diabetes and endoplasmic reticulum stress

Diabetes is a widespread disease characterized by high blood glucose levels due to abnormal insulin activity, production, or both. Chronic diabetes causes many secondary complications including cardiovascular disease: a life-threatening complication. Cerebral ischemia-related mortality, morbidity, and the extent of brain injury are high in diabetes. However, the mechanism of increase in ischemic brain injury during diabetes is not well understood. Multiple mechanisms mediate diabetic hyperglycemia and hypoglycemia-induced increase in ischemic brain injury. Endoplasmic reticulum (ER) stress mediates both brain injury as well as brain protection after ischemia-reperfusion injury. The pathways of ER stress are modulated during diabetes. Free radical generation and mitochondrial dysfunction, two of the prominent mechanisms that mediate diabetic increase in ischemic brain injury, are known to stimulate the pathways of ER stress. Increased ischemic brain injury in diabetes is accompanied by a further increase in the activation of ER stress. As there are many metabolic changes associated with diabetes, differential activation of the pathways of ER stress may mediate pronounced ischemic brain injury in subjects suffering from diabetes. We presently discuss the literature on the significance of ER stress in mediating increased ischemia-reperfusion injury in diabetes. [Display omitted] •The mechanism of increased ischemic brain injury in diabetes is not well understood.•Endoplasmic reticulum (ER) stress is an important mechanism of ischemic brain injury.•The pathways of ER stress are modulated during diabetes.•Diabetic increase in ischemic injury occurs along with enhanced ER stress activation.•ER stress activation may mediate pronounced ischemic brain injury in diabetes