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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1996-11-13
pubmed:abstractText
Nitroxide stable radicals are unreactive toward most diamagnetic molecules, but readily undergo one-electron redox reactions with paramagnetic species such as free radicals and transition metals, thus serving as cell permeable antioxidants. The involvement of reactive oxygen species in the pathophysiology of neurotrauma has been well established. The neuroprotective properties of three nitroxides: 2,2,6,6-tetramethylpiperidine-1-N-oxyl (TPO), the hydrophilic analog: TPL, and its reduced form: TPH, were tested in a rat model of closed head injury (CHI). CHI was induced in ether anesthetized rats by a weight drop device and recovery was followed for up to 24 h. The "clinical status' was evaluated according to a "Neurological Severity Score' (NSS), at 1 h and 24 h, the difference between these scores, delta NSS, reflecting the extent of recovery. Edema was assessed by measurement of water content at 24 h. The integrity of the blood-brain barrier (BBB) was investigated using Evans Blue extravasation. TPL, TPH and TPO facilitated clinical recovery, the latter causing a more pronounced effect (delta NSS = 7.63 +/- 0.26 in treated rats vs 4.94 +/- 0.48 in control rats, P < 0.001). TPL was found to significantly reduce edema formation (80.13% +/- 0.26 vs 83.65% +/- 0.49, P < 0.001) and to ameliorate BBB disruption (P < 0.001). The therapeutic window of TPL was found to be in the range of 4 h after CHI. The mechanisms underlying the nitroxide neuroprotective activity presumably involve: (a) reoxidation of reduced transition metal ions; (b) a selective radical-radical reaction; and (c) catalytic removal of intracellular and extracellular .O2-. The results indicate that nitroxides could be used in neuroprotective treatment of CHI.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
717
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Cerebroprotective effect of stable nitroxide radicals in closed head injury in the rat.
pubmed:affiliation
Department of Pharmacology, Faculty of Medicine, Hebrew University, School of Pharmacy, Jerusalem, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't