Document Detail

Neuroprotective properties of different anesthetics on axotomized rat retinal ganglion cells in vivo.
MedLine Citation:
PMID:  14987467     Owner:  NLM     Status:  MEDLINE    
Following transection of the optic nerve (ON) in the adult rat, 85% of axotomized retinal ganglion cells (RGCs) undergo degeneration within 14 days. Here, we examined the effects of various anesthetic and analgesic compounds on the number of RGCs surviving ON lesion. Five different protocols for rodent anesthesia were used (A, chloral hydrate; B, chloral hydrate/carprofen; C, chloral hydrate/buprenorphine; D, ketamine/xylazine; E, fentanyl/medetomidin/midazolam), and the numbers of RGCs surviving 14 days after ON axotomy were compared to evaluate if the agents used may affect numbers of surviving RGCs. In many laboratories, rodent ON surgery is performed with chloral hydrate anesthesia, and this condition was used as baseline, with 343.7 +/- 29.1 RGCs/mm(2) surviving after 14 days. The addition of carprofen to chloral hydrate did not affect RGC numbers (382.7 +/- 15.2 RGCs/mm(2); n.s.), while chloral hydrate with buprenorphine (421.1 +/- 25.1 RGCs/mm(2); p < 0.05), ketamine and xylazine (403.6 +/- 36.1 RGCs/mm(2); p < 0.05), or fentanyl with medetomidine and midazolam (481.3 +/- 10.4 RGCs/mm(2); p < 0.05) all increased RGC survival. In a second series of experiments, ON axotomized rats were treated with an adenoviral vector expressing GDNF (Ad.GDNF) that rescues injured RGCs, to study if the anesthetics (A, B, E; see above) would influence the degree of RGC neuroprotection afforded by GDNF. Intravitreal injection of Ad.GDNF at a low titre rescued approximately 10% of RGCs that would have degenerated without treatment using either of the three different anesthesia protocols, yet GDNF did not exert synergistic neuroprotection with any of the anesthetics tested. Our results indicate that in combination carprofen and chloral hydrate, while affording safe and reliable anesthesia and analgesia for rat ON surgery, does not affect the numbers of surviving RGCs. Therefore, data obtained with this combination may be related to experimental data obtained previously with only chloral hydrate anesthesia. All other protocols afforded some degree of RGC neuroprotection that may be utilized for experimental therapies of neurodegeneration, yet needs to be taken into careful consideration when mechanisms of neurodegeneration or approaches towards neuroprotection of RGCs are examined.
Sidar Ozden; Stefan Isenmann
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurotrauma     Volume:  21     ISSN:  0897-7151     ISO Abbreviation:  J. Neurotrauma     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-02-27     Completed Date:  2004-05-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8811626     Medline TA:  J Neurotrauma     Country:  United States    
Other Details:
Languages:  eng     Pagination:  73-82     Citation Subset:  IM    
Neuroregeneration Laboratory, Department of Neurology, University of Jena, Jena, Germany.
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MeSH Terms
Anesthetics / pharmacology*
Blotting, Western
Caspase 3
Caspases / metabolism
Cell Death / drug effects,  physiology
Cell Survival / drug effects,  physiology
Drug Therapy, Combination
Gene Expression
Glial Cell Line-Derived Neurotrophic Factor
Nerve Growth Factors / genetics,  pharmacology
Neuroprotective Agents / pharmacology*
Optic Nerve / surgery*
Rats, Sprague-Dawley
Retinal Ganglion Cells / drug effects*
Reg. No./Substance:
0/Anesthetics; 0/Gdnf protein, rat; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/Nerve Growth Factors; 0/Neuroprotective Agents; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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