Vinod Kumar Tewari1, Vivek Bhosale2, Rakesh Shukla3, Hari Kishan Das Gupta4. 1. Neurosurgeon, Department of Neurosurgery, Advance Neuro and General Hospital, Lucknow, Uttar Pradesh, India. 2. Scientist, Department of Clinical and Experimental Medicine, Sir-Central Drug Research Institute, Lucknow, Uttar Pradesh, India. 3. Chief Scientist and Head, Department of Pharmacology, CSIR-CDRI, Lucknow, Uttar Pradesh, India. 4. Mch Urologist Head, Department of Surgery, Jhalawar Medical College, Jhalawar, Rajasthan, India.
Abstract
INTRODUCTION: Ischemic stroke at later stages (>4.5 hour) have very few treatment options left. In those cases Nitric Oxide (NO) may provide promising results. NO is active in signaling pathways. Sodium Nitroprusside (SNP), a NO donor was tested earlier in rat Middle Cerebral Artery Occlusion (MCAO) model in early stages (5-60 minutes) and found useful but in delayed stroke cases (60-120 minutes) found useless. This was due to local inducible Nitric Oxide Synthase Enzyme (iNOS) and superoxide (causes destructive effect) formation which was skipped. AIM: To evaluate the effect of Intracarotid Sodium Nitroprusside (ICSNP) in MCAO rat model of ischemic stroke (I/R model) fifth post ischemic stroke day. MATERIALS AND METHODS: A total of 24 Sprague Dawley rats, weighing 250 gm to 280 gm, at CDRI-Lucknow, India were used. Rats were divided in three groups. Group A (n=4) were taken as sham with standard procedure but without any injection on fifth day, Group B (n=8) as control with injection of saline on fifth day and Group C (n=12) received SNP at dose of 3 mcg/kg/minute given directly in internal carotid artery via External Carotid Artery (ECA) with a modified intraluminal stump technique as Ischemia/Reperfusion (I/R) in ipsilateral MCAO at intracarotid artery region as a single dose therapy on fifth day and then wound was closed. Waited for full recovery for two hours, then neurobehavioural assessment scores were noted. Thereafter, the brains were quickly removed and sliced at 2 mm intervals. Animals showing no sign of neurological deficit, were excluded from the study. Tested animals were compared with control animals for neurological deficit, percentage of infarction by 2,3,5-Triphenyl Tetrazolium Chloride (TTC) staining, nNOS expression and scores were summed up. The statistical analysis was done by Newman-Keuls test, Graph Pad prism (version.5.0) and p<0.05 was considered statistically significant. RESULTS: ICSNP group (Group C) showed a good reduction in the cerebral infarction of 53.42% as compared to control (Group B). Group A mean change in Newman-Keuls test and Graph Pad prism (version.5.0) was showing increase of 1.44 points/6.55%, compared to Group B decrease of 0.7 points. A 60% decrease in ischemic zone noted in Group A. CONCLUSION: The use of single dose ICSNP is beneficial (53.42%) in fifth post stroke day.
INTRODUCTION:Ischemic stroke at later stages (>4.5 hour) have very few treatment options left. In those cases Nitric Oxide (NO) may provide promising results. NO is active in signaling pathways. Sodium Nitroprusside (SNP), a NO donor was tested earlier in ratMiddle Cerebral Artery Occlusion (MCAO) model in early stages (5-60 minutes) and found useful but in delayed stroke cases (60-120 minutes) found useless. This was due to local inducible Nitric Oxide Synthase Enzyme (iNOS) and superoxide (causes destructive effect) formation which was skipped. AIM: To evaluate the effect of Intracarotid Sodium Nitroprusside (ICSNP) in MCAOrat model of ischemic stroke (I/R model) fifth post ischemic stroke day. MATERIALS AND METHODS: A total of 24 Sprague Dawley rats, weighing 250 gm to 280 gm, at CDRI-Lucknow, India were used. Rats were divided in three groups. Group A (n=4) were taken as sham with standard procedure but without any injection on fifth day, Group B (n=8) as control with injection of saline on fifth day and Group C (n=12) received SNP at dose of 3 mcg/kg/minute given directly in internal carotid artery via External Carotid Artery (ECA) with a modified intraluminal stump technique as Ischemia/Reperfusion (I/R) in ipsilateral MCAO at intracarotid artery region as a single dose therapy on fifth day and then wound was closed. Waited for full recovery for two hours, then neurobehavioural assessment scores were noted. Thereafter, the brains were quickly removed and sliced at 2 mm intervals. Animals showing no sign of neurological deficit, were excluded from the study. Tested animals were compared with control animals for neurological deficit, percentage of infarction by 2,3,5-Triphenyl Tetrazolium Chloride (TTC) staining, nNOS expression and scores were summed up. The statistical analysis was done by Newman-Keuls test, Graph Pad prism (version.5.0) and p<0.05 was considered statistically significant. RESULTS:ICSNP group (Group C) showed a good reduction in the cerebral infarction of 53.42% as compared to control (Group B). Group A mean change in Newman-Keuls test and Graph Pad prism (version.5.0) was showing increase of 1.44 points/6.55%, compared to Group B decrease of 0.7 points. A 60% decrease in ischemic zone noted in Group A. CONCLUSION: The use of single dose ICSNP is beneficial (53.42%) in fifth post stroke day.
Authors: Hülya Bayir; Valerian E Kagan; Grigory G Borisenko; Yulia Y Tyurina; Keri L Janesko; Vincent A Vagni; Timothy R Billiar; Deborah L Williams; Patrick M Kochanek Journal: J Cereb Blood Flow Metab Date: 2005-06 Impact factor: 6.200