Withanolide a penetrates brain via intra-nasal administration and exerts neuroprotection in cerebral ischemia reperfusion injury in mice.

1. Withanolide A (WA), a major constituent phytochemical of the Ayurvedic herb Withania somnifera reportedly combats neurodegeneration in Alzheimer's disease and Parkinson's disease. But no study has yet reported the ability of WA in crossing the blood-brain barrier (BBB). The present study analyses the brain penetration ability of WA after intra-nasal administration and assesses its neuroprotective ability in cerebral ischemia-reperfusion injury in adult mice model.2. Brain penetration of WA after intranasal administration in cortex and cerebellum was assessed using HPLC-UV. Three different doses (1 mg/kg, 5 mg/kg and 10 mg/kg) of the phytochemical were used to study the neuroprotective ability of WA by evaluating the brain damage, changes in cerebral neurotransmitter levels and brain tissue morphology.3. Intranasal administration of the phytochemical facilitates its penetration in the cortex and cerebellum. Post-treatment with WA significantly reduced cerebral infarction, restored BBB disruption and cerebral oedema. The WA post-treatment also lowered the ischemia-induced elevated neurotransmitter and biochemical levels in brain compartments. The highest dose (10 mg/kg) of WA also markedly reduced the morphological damages, apoptotic and necrotic cell death in brain tissue occurring due to cerebral ischemia pathophysiology.4. Intra-nasal administration enables brain penetration of WA and allows the phytochemical to exert neuroprotective ability in the global cerebral ischemia model.

Prolactin attenuates global cerebral ischemic injury in rat model by conferring neuroprotection.

Primary Objective: Limited available therapeutics for ischemic stroke necessitate dire need of designing novel strategies for combating ischemic pathophysiological cascade among which neuroprotective strategies emerge as positive approaches. The neuropeptide prolactin is a pleiotropic hormone that affects various physiological conditions and reportedly combats neurotoxicity, neuronal stress and provides neuroprotection to hippocampal neurons in vitro.Research Design: The study explores the ability of prolactin in conferring neuroprotection in global cerebral ischemia in vivo and attempts to optimize the dose of prolactin which will be effective for the same.Methods and Procedure: Global cerebral ischemia was induced in male rats by bilateral common carotid occlusion (BCCAO) and different physiological and biochemical parameters were evaluated. Also, cerebral infarction and percentage of brain edema were measured.Results: The results revealed that prolactin significantly reduces cerebral infarct, brain water content and restores the physiological conditions like blood pressure, heart rate and cerebral blood flow. Also, prolactin markedly reduces the increased levels of the neurotransmitters (É£-aminobutyric acid and glutamate), cerebral calcium and nitrate in different brain compartments of ischemic rats.Conclusion: Prolactin is able to ameliorate ischemia-reperfusion injury in rat brain and might be a potent candidate for further neuro-therapeutics development.

Pharmacokinetics and brain penetration study of chlorogenic acid in rats.

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 tmax of 1 min similar to IV route after IN administration. The peak plasma concentration and AUC0-24 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 (AUCbrain, IN) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUCbrain, IV) 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.

Prolapsing cystitis cystica causing bladder outlet obstruction: An unusual complication.

Cystitis cystica (CC) is aproliferative disorder of bladder urothelium and usually subsides with medical therapy. However, this is not true for severe CC where surgical intervention is required to control breakthrough urinary tract infection (UTI). It may be mistaken as bladder neoplasm or posterior urethral valve, especially in children. Here, we report a case of CC in a 2-year-old boy where we had to excise the large pedunculated intravesical lesion to control breakthrough UTI and ongoing renal damage.

Changes in electrolyte concentrations alter the impedance during ischemia-reperfusion injury in rat brain.

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.

Neuroprotective effect of chlorogenic acid in global cerebral ischemia-reperfusion rat model.

The ischemic cascade is initiated in the hypoperfused region of the brain that leads to neuronal cell death. Identification of multi-target inhibitor against prominent molecular mediators of ischemic cascade might be a suitable strategy to combat cerebral ischemic stroke. The present study is designed to evaluate the neuroprotective efficacy of chlorogenic acid (CGA) in the global cerebral ischemic rat model. The effective dose of CGA was evaluated on the basis of reduction in cerebral infarction area percentage, Evans blue extravasation, and restoration of brain water content. The expression of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and caspase-3 was evaluated by immunohistochemistry and morphological and cellular alterations in the cortex were observed by brain histology. The level of glutamate, calcium, and nitrate in different regions of the brain, as well as cerebrospinal fluid (CSF), was evaluated. The level of calcium and nitrate was compared with ifenprodil-an antagonist of N-methyl-D-aspartate receptor (NMDAR) and 7-nitroindazole-an inhibitor of neuronal nitric oxide synthase (nNOS) respectively. Further, molecular docking was performed to compare the inhibition potential of CGA against NMDAR and nNOS with their inhibitors. Dose optimization results revealed that intranasal administration of CGA (10 mg/kg b.w.) significantly reduced the cerebral infarction area, Evans blue extravasation and restored the brain water content compared with ischemia group. It also significantly reduced the calcium, nitrate, and glutamate levels compared with ischemia group in the cortex, hippocampus cerebellum, and CSF. Immunohistochemical analysis revealed that CGA significantly reduced the expression of TNF-α, iNOS, and caspase-3 as compared with the ischemia group. In molecular docking study, CGA displayed similar binding interaction as that of Ifenprodil and 7-nitroindazole with NMDAR and nNOS respectively. The current findings suggest that the treatment with CGA confers neuroprotection in global ischemic insult by inhibiting and downregulating the different molecular markers of cerebral ischemia.

Isolated Mediastinal Pseudocyst of the Pancreas.

BACKGROUND: Mediastinal pancreatic pseudocyst is a rare complication of pancreatitis. CASE CHARACTERISTICS: An 8-year-old boy with chest pain and shortness of breath. Computed tomography of chest showed a cystic mass in the mediastinum. The cyst aspirate revealed high amylase and lipase levels, suggestive of pancreatic pseudocyst. OUTCOME: The patient gradually recovered after Roux-en-Y cystojejunostomy. MESSAGE: Cysto-jejunostomy is a viable treatment option for mediastinal pancreatic pseudocyst, especially with failure of medical therapy.