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1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles-Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path. 2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10 mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method. 3. The study observes that CGA is rapidly absorbed in plasma with t of 1 min similar to IV route after IN administration. The peak plasma concentration and AUC are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route. 4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360 min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUC) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUC) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders.

Objective: Ischemic stroke is a major cause of death and disability worldwide. Nowadays, electrical impedance spectroscopy is an emerging tool to differentiate between normal and stroke conditions. Approach: In this study, changes in the bio-impedance spectroscopy using a two-electrode method with varying frequencies from 100 to 35 kHz have been assessed in a model of global cerebral ischemia in anesthetized rats during normal, occlusion and reperfusion conditions. Global cerebral ischemia was induced by bilateral common carotid artery occlusion for 40 min following 40 min of reperfusion. The concentration of sodium, potassium, calcium and chloride ions in the whole rat brain was determined by electrolyte analyzer. For the interpretation of in vivo results, changes in electrical impedance with varying concentrations of sodium, potassium and calcium ions in artificial cerebrospinal fluid (aCSF) were also observed using the bio-impedance spectroscopy method. Main results: The in vivo bio-impedance analysis suggests that the impedance is consistently increased during occlusion as compared to the normal condition. The in vitro study revealed that the impedance escalates with an increase in the concentration of potassium and calcium ions and reduces with an increase in the concentration of sodium ions in aCSF. A further electrolyte analysis suggested that the level of sodium and chloride ions is significantly decreased and the level of calcium and potassium is significantly increased during occlusion as compared to the normal condition. Significance: These findings suggest that the increase in impedance during occlusion may be due to changes in the ionic concentration of the rat brain. The above in vivo and in vitro studies successfully demonstrated and interrelated the change in impedance with corresponding changes in ionic concentration.

Evaluation of Low Doses of Neostigmine for Reversal of Residual NeuromuscularBlockade 2/5

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