Brain Disorders & Therapy

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

Global Summit on Stroke

August 03-05, 2015 Birmingham, UK

Vinod Tewari

Scientific Tracks Abstracts: Brain Disord Ther

Abstract:

Background: rTPA showed level-1 benefit 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 affinity for NO than for oxygen (10,000-fold-effect).
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: After 90-seconds in ICSNP group, mean change in NIHSS score decreased by 1.44-points/6.55%; after 2 hour,
decreased by 1.16-points; after 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 after 24 hours then to normal in due course.