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Vinod Tewari

Vinod Tewari

Neuro Center, India

Title: The 10,000 fold effect of retrograde neurotransmission, a new concept for stroke revival: Use of intracarotid sodium nitroprusside

Biography

Biography: Vinod Tewari

Abstract

Background: rTPA showed level-1 benefi t in AIS. Intracarotid-sodium-nitroprusside (ICSNP)studied here for widetreatment- window and fast-recovery. 1. Retrograde-Neurotransmission-RNT (acute); Normal-impulse: At synaptic-level, glutamate-activates NMDA-receptors having nitric-oxide-synthetase (NOS) on post synaptic-neuron, for further propagation by calcium-calmodulin complex. Nitric-oxide (NO-produced-by-NOS) travels-backward across chemical-synapse (CS), binds NO-receptor/sGC of presynaptic-neuron, regulating anterograde-neurotransmission (ANT). Heme (ligand-binding-site) exhibits >10,000-fold higher affi nity for NO than for oxygen (10,000-fold-eff ect). Stroke: Normal synaptic-activity, ANT and RNT are absent. NO-donor (SNP) releases NO from NOS. NO travels backward across CS to bind heme of NO-receptor/sGC, generates Electrical-Impulse as in normal-ANT. Vasospasm (acute): Juxtrapenumbra- perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP-pathway. Long-Term Potentiation (LTP) chronic: Via NO–cGMP-pathway. Aims/Study design: To treat acute-stroke by RNT/vasodilatation and chronic-stroke by LTP. Case control prospective study. Materials & Methods: 200-patients (100-control and 100 patients ICSNP group). Mean time for superfusion was 9.5 days poststroke. Status was monitored by NIHSS, MRI and TCD. Results: Aft er 90-seconds in ICSNP group, mean change in NIHSS score decreased by 1.44-points/6.55%; aft er 2 hour, decreased by 1.16-points; aft er 24 hour, increased by 0.66-points/2.25%, compared to control-group increase of 0.7 points or 3.53%; at 7 days, 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points or 22.37%; at 2 months 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points or 8.78%. Conclusions: ICSNP is a swift -acting drug in the treatment of stroke, acting within 90 seconds on 9.5 post-stroke days with a small decrease aft er 24 hours then to normal in due course.