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An improved method of transcutaneous cisterna magna puncture for cerebrospinal fluid sampling in rats.
MedLine Citation:
PMID:  23000275     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A simple, reproducible and chronic technique of cerebrospinal fluid (CSF) collection in rats was developed by direct cisterna magna (CM) puncture utilizing stereotaxic apparatus. CSF collection apparatus was constructed using 1mL syringe, silicone tubing, 21G disposable needle and water. Animal was placed on an elevated platform over stereotaxic apparatus base and puncture site was identified with the aid of stereotaxic co-ordinates. The volume of CSF collected varied from 100-180μL with mean CSF volume of 150μL. Neurological deficits were recorded according to the modified Bederson's scoring system 24h post CSF collection and differential cell count in CSF samples was performed. Animals continued to be normal with regular feed intake and gained body weight (∼24%) even after repeated sampling for four weeks and showed no severe neurological deficits (mean Bederson score<1 for four weeks). Neuropharmacokinetic data for Phenytoin sodium, MS 275 and Valproic acid (VPA) demonstrated CSF uptake with CSF(AUC)/Plasma(AUC) ratio (K(p), (CSF)) of 0.09, 0.01 and 0.33, respectively. This model exemplifies the 3R's of animal use and has been successfully implemented at Orchid Chemicals and Pharmaceuticals Limited for lead optimization of CNS penetrating HDAC inhibitors.
Authors:
Mahamad Yunnus A Mahat; N Fakrudeen Ali Ahamed; S Chandrasekaran; Sridharan Rajagopal; Shridhar Narayanan; Narayanan Surendran
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-19
Journal Detail:
Title:  Journal of neuroscience methods     Volume:  -     ISSN:  1872-678X     ISO Abbreviation:  J. Neurosci. Methods     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905558     Medline TA:  J Neurosci Methods     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Department of DMPK, Pre-Formulation and Bioanalytical, Drug Discovery Research, R & D Center, Orchid Chemicals and Pharmaceuticals Limited, Sozhanganallur, Chennai-600119. Tamil Nadu, India.
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