The present study has been designed to pharmacologically investigate the role of mast cell degranulation in ischemic preconditioning-induced reversal of global ischemia- and reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24 h was employed in present study to produce ischemia- and reperfusion-induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using Morris water-maze test. Rota-rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor coordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min (ischemic preconditioning) prevented markedly ischemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of memory and motor coordination. Sodium cromoglycate (10 mg/kg, i.p.), a mast cell stabilizer attenuated the neuroprotective effect of ischemic preconditioning. It is concluded that neuroprotective effect of ischemic preconditioning may be due to the degranulation of mast cells.
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.
The present study was designed to investigate the effect of diethyl dithiocarbamic acid sodium salt trihydrate (DDA), a selective inhibitor of nuclear factor-kappa-B, on the development of morphine dependence in a mouse model of naloxone-induced opioid withdrawal syndrome. Morphine (5 mg/kg, intraperitoneally) was administered twice daily for a period of 5 days, after which a single injection of naloxone (8 mg/kg, intraperitoneally) precipitated an opioid withdrawal syndrome in mice. Behavioral observations were made for a period of 30 min immediately after naloxone treatment. Withdrawal syndrome was quantitatively assessed in terms of withdrawal severity score and the frequency of jumping, rearing, forepaw licking, and circling. DDA markedly and dose-dependently (P<0.01) attenuated the morphine-naloxone-induced experimental opioid withdrawal syndrome. However, DDA administration did not alter locomotor activity, thus ruling out any sedative action of DDA per se. Further, DDA pretreatment did not alter the acute analgesic effect of morphine. The results suggest that nuclear factor-kappa-B is involved in the development of opioid dependence and the precipitation of its withdrawal syndrome, and thus, may serve as a viable pharmacological target to tackle the problem of opioid addiction.
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