***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND AND PURPOSE Parenterally administered MgSO4 is neuroprotective in st and ard animal models of focal cerebral ischemia and in many other paradigms of brain injury . Previous small clinical trials in stroke patients have explored the safety and tolerability of different infusion regimens . This study was undertaken to optimize the regimen for a multicenter trial . METHODS Within 24 hours of the onset of clinical ly diagnosed stroke , patients were r and omized to receive placebo or one of three intravenous MgSO4 infusions : a loading infusion of 8 , 12 , or 16 mmol , followed by 65 mmol over 24 hours . Cardiovascular parameters , serum magnesium concentrations , and blood glucose concentrations were determined . Outcome at 30 and 90 days was recorded . RESULTS Twenty-five patients were recruited and treated at a mean time of 20 hours after stroke . No tolerability problems were identified . No effects of magnesium on heart rate , blood pressure , or blood glucose were evident . Serum magnesium concentrations rose to target levels most rapidly in the highest loading infusion group and were maintained in all groups for at least 24 hours . CONCLUSIONS MgSO4 infusions that rapidly elevate the serum magnesium concentration to potentially therapeutic levels are well tolerated and have no major hemodynamic effects in patients with acute stroke . The 16-mmol loading infusion achieved target serum concentrations most rapidly and has been chosen for further trials BACKGROUND AND PURPOSE We sought to evaluate the effects of the combination of cytidine-5'-diphosphocholine ( citicoline ) and thrombolysis on infa rct size , clinical outcome , and mortality in a rat embolic stroke model . METHODS Eighty-three Sprague-Dawley rats were embolized in the carotid territory with a single fibrin embolus and r and omly assigned to the following treatment groups : ( 1 ) control ( saline ) , ( 2 ) citicoline 250 mg/kg , ( 3 ) citicoline 500 mg/kg , ( 4 ) recombinant tissue plasminogen activator ( rtPA ) 5 mg/kg , ( 5 ) rtPA 5 mg/kg plus citicoline 250 mg/kg , and ( 6 ) rtPA 5 mg/kg plus citicoline 500 mg/kg . rtPA was administered as a continuous intravenous infusion over 45 minutes starting 45 minutes after embolization ; citicoline was given intraperitoneally 30 minutes and 24 , 48 , and 72 hours after embolization . At 96 hours , the brains were fixed and stained by hematoxylin-eosin , and infa rct volumes were measured . Neurological scores were determined daily . RESULTS The median infa rct size , measured as percentage of the affected hemisphere , in the control group was 37 % ( interquartile range , 26 % to 69 % ) compared with 22 % ( 5 % to 52 % ; P = NS ) in group 2 , 11 % ( 5 % to 34 % ; P = NS ) in group 3 , 24 % ( 12 % to 31 % ; P = NS ) in group 4 , 11 % ( 3 % to 22 % ; P=0.02 ) in the combined group 5 , and 19 % ( 9 % to 51 % ; P = NS ) in group 6 . The infa rct size was significantly reduced in the combined citicoline+rtPA-treated groups to a median of 13 % ( 5 % to 30 % ; P<0.01 ) . Citicoline 500 mg/kg and citicoline combined with rtPA also promoted functional recovery . CONCLUSIONS These results demonstrate that the combination of low-dose citicoline and rtPA significantly reduced infa rct size in this focal ischemia model A r and omized , placebo-controlled , double-blind study was performed as a pilot study to examine the benefit of the administration of magnesium sulfate given intravenously as a protective substance during the first 24 hours following a stroke . Patients who had cortical infa rct ion in the middle cerebral artery territory with moderate to severe neurologic deficits lasting for more than 15 minutes with onset less than 24 hours were included . The patients were treated with magnesium sulfate or placebo for 5 days and examined by a blinded investigator . Patients had follow-up for 30 days . The primary efficacy variable was the proportion of patients reaching mild to moderate neurologic deficit on the Orgogozo scale ( 80 points ) and relative functional independence on the Barthel index ( 60 points ) . Orgogozo scale and Mathew scale values were obtained on admission and days 2 , 4 , 8 , and 30 after stroke . Barthel activities of daily living index and Rankin disability score were obtained on day 30 . Forty-one patients ( 22 given treatment and 19 given placebo )  demonstrated significant beneficial effects on the Orgogozo scale ( 84 ± 11 vs. 64 ± 10 , p < 0.0001 ) and ( 83 ± 14 vs. 70 ± 15 , p < 0.009 ) , respectively . At the end of 1-month follow-up , the Barthel ADL index was nonsignificantly higher and the Rankin disability score was marginally significantly lower in the magnesium-treated group ( 84 ± 26 vs. 71.8 ± 26 , p < 0.143 ) than in control subjects ( 2.3 ± 1.1 vs. 3 ± 1.3 , p < 0.077 ) . Intravenous magnesium sulfate had significant positive effect on the outcome in patients with acute stroke . Further studies on a larger scale are needed to confirm these findings BACKGROUND AND PURPOSE Based on neuroprotective efficacy in animal models , we evaluated the N-methyl D-aspartate antagonist Selfotel in patients with ischemic stroke , after doses up to 1.5 mg/kg were shown to be safe in phase 1 and phase 2a studies . METHODS Two pivotal phase 3 ischemic stroke trials tested the hypothesis , by double-blind , r and omized , placebo-controlled parallel design , that a single intravenous 1.5 mg/kg dose of Selfotel , administered within 6 hours of stroke onset , would improve functional outcome at 90 days , defined as the proportion of patients achieving a Barthel Index score of > /=60 . The trials were performed in patients aged 40 to 85 years with acute ischemic hemispheric stroke and a motor deficit . RESULTS The 2 trials were suspended on advice of the independent Data Safety Monitoring Board because of an imbalance in mortality after a total enrollment of 567 patients . The groups were well matched for initial stroke severity and time from stroke onset to therapy . There was no difference in the 90-day mortality rate , with 62 deaths ( 22 % ) in the Selfotel group and 49 ( 17 % ) in the placebo-treated group ( RR=1.3 ; 95 % CI 0.92 to 1.83 ; P=0.15 ) . However , early mortality was higher in the Selfotel-treated patients ( day 30 : 54 of 280 versus 37 of 286 ; P=0.05 ) . In patients with severe stroke , mortality imbalance was significant throughout the trial ( P=0.05 ) . CONCLUSIONS Selfotel was not an effective treatment for acute ischemic stroke . Furthermore , a trend toward increased mortality , particularly within the first 30 days and in patients with severe stroke , suggests that the drug might have a neurotoxic effect in brain ischemia The Intravenous Magnesium Efficacy in Acute Stroke ( IMAGES ) trial is a multicentre , r and omised , placebo-controlled trial of magnesium sulphate ( MgSO4 ) funded by the UK Medical Research Council . When complete , it will be the largest single neuroprotective study undertaken to date . Conscious patients presenting within 12 h of acute stroke with limb weakness are eligible . The primary outcome measure is combined death and disability as measured using the Barthel Index at 90-day follow up . By r and omizing 2700 patients , the study will have 84 % power to detect a 5.5 % absolute reduction in the primary end-point . By April 2000 , 86 centres were participating , with representation in Canada , USA , Europe , South America , Singapore and Australia . So far , 1206 patients have been r and omised , of whom 37 % were treated within 6 h. Overall 3-month mortality was 20 % and the primary outcome event rate was 43 % . The study is ongoing and centres worldwide are encouraged to participate Increasing evidence suggests a neuroprotective potential of magnesium sulfate ( MgSO4 ) . Only limited information about the passage of MgSO4 to the cerebrospinal fluid ( CSF ) is available in neurosurgical patients . However , with regard to the clinical relevance of magnesium 's neuroprotective properties , quantitative data about its CSF passage are needed . The present study aims to assess the amount and the time course of magnesium 's CSF passage in neurosurgical patients . To this end , 20 patients undergoing general anesthesia for neurosurgery and needing CSF drainage were included . Patients received an i.v . bolus of 60 mg/kg MgSO4 . The increase in plasma and CSF magnesium concentration were measured 30 , 90 , and 240 min after the end of the MgSO4 infusion . These values were compared with the baseline levels taken before the start of the MgSO4 infusion . Thus , each patient served as his or her own control . Values are expressed as means + /- SD . The plasma magnesium levels were measured as follows : baseline , 0.74 + /- 0.12 mM ; at 30 min , 1.24 + /- 0.1 mM ( p < 0.01 ) ; at 90 min , 0.95 + /- 0.15 mM ( p < 0.01 ) , and at 240 min , 0.82 + /- 0.14 mM ( p < 0.05 ) . The CSF magnesium levels were measured as follows : baseline , 0.95 + /- 0.11 mM ; at 30 min , 1.00 + /- 0.15 mM ( NS ) ; at 90 min , 1.10 + /- 0.17 mM ( p < 0.01 ) ; and at 240 min , 1.13 + /- 0.19 mM ( p < 0.001 ) . We concluded that a bolus of 60 mg/kg of MgSO4 leads at least after 90 min to a significant increase in the CSF magnesium concentration . Moreover , the increase in plasma and CSF magnesium concentration is not parallel . Thus , plasma magnesium concentration can not be used to predict the changes in CSF concentrations Recent brain research proposes that , during ischemia , synaptically released excitatory amino acid neurotransmitters accumulate at toxic concentrations with ensuing neuronal death . Their action is mediated by the receptor subtype N-methyl-D-aspartate ( NMDA ) . The protective effect of NMDA receptor blockade with intrathecal MgSO4 and MK-801 was investigated during spinal cord ischemia induced by aortic occlusion of 12 minutes . Male Sprague-Dawley rats , 250 - 300 g , underwent intrathecal administration of 20 microL of normal saline ( SA n = 16 ) , MgSO4 1 M ( MG n = 16 ) , or MK-801 , 25 mM solutions ( MK n = 16 ) in a r and omized order . After 2 hours , the animals underwent occlusion of the thoracic aorta and subclavian arteries for 12 min . An additional control group ( CO n = 16 ) underwent occlusion for 12 minutes , without intrathecal injection . The animals were scored according to their functional performance ( LS = lesion score ) each day for four days by a blinded observer . Mean LS were calculated for each group at a given day . Treatment and control groups were not different at day 1 ( P = 0.302 ) . Group MG was improved from groups SA ( P = < 0.0039 ) and CO ( P = < 0.0048 ) at day 4 . This study demonstrates that although intrathecal NMDA receptor blockade with MgSO4 or MK-801 does not prevent  paraplegia due to spinal cord ischemia in the rat , it could however influence the rate of recovery after ischemic injury Magnesium ( Mg ) has shown the ability to inhibit arterial thrombus formation in some experimental animal studies . This effect may be due to an inhibition of platelet reactivity as in vitro studies have demonstrated that Mg inhibits platelet aggregation . In order to evaluate the in vivo effect of Mg in humans measurements of platelet activity , fibrinolytic activity , as well as measurements of prostacyclin ( PGI2 ) , and nitric oxide ( NO ) release were performed after infusion of magnesium sulphate ( MgSO4 ) in healthy volunteers . In a placebo controlled , cross-over study in 14 healthy male subjects , 8 mmol MgSO4 was given as an intravenous 
    Output:
    
Systemically administered magnesium at doses that double physiological serum concentration significantly reduces infa rct volume in animal models of stroke , with a window of up to six hours after onset and favourable dose-response characteristics when compared with previously tested neuroprotective agents .