PMID- 9183363
OWN - NLM
STAT- MEDLINE
DCOM- 19970701
LR  - 20220408
IS  - 0039-2499 (Print)
IS  - 0039-2499 (Linking)
VI  - 28
IP  - 6
DP  - 1997 Jun
TI  - Nitric oxide synthase in models of focal ischemia.
PG  - 1283-8
AB  - BACKGROUND AND PURPOSE: Cessation of blood flow to the brain, for even a few 
      minutes, sets in motion a potential reversible cascade of events resulting in 
      neuronal cell death. Oxygen free radicals and oxidants appear to play an 
      important role in central nervous system injury after cerebral ischemia and 
      reperfusion. Recently, divergent roles for the newly identified neuronal 
      messenger molecule and oxygen radical, nitric oxide (NO), have been identified in 
      various models of cerebral ischemia. Because of the chemical and physical 
      properties of NO, the numerous physiological activities it mediates, and the lack 
      of specific agents to modulate the activity of the different isoforms of NO 
      synthase (NOS), reports regarding the role of NO in focal cerebral ischemia have 
      been confounding and often conflicting. Recent advances in pharmacology and the 
      development of transgenic knockout mice specific for the different isoforms of 
      NOS have advanced our knowledge and clarified the role of NO in cerebral 
      ischemia. METHODS: Animal models of focal ischemia employ occlusion of nutrient 
      cerebral vessels, most commonly the middle cerebral artery. Primary cortical 
      cultures are exposed to excitotoxic or ischemic conditions, and the activities of 
      NOS isoforms or NO production are evaluated. Transgenic mice lacking expression 
      of either the neuronal isoform of NOS (nNOS), the endothelial isoform of NOS 
      (eNOS), or the immunologic isoform of NOS (iNOS) have been examined in models of 
      excitotoxic injury and ischemia. RESULTS: Excitotoxic or ischemic conditions 
      excessively activate nNOS, resulting in concentrations of NO that are toxic to 
      surrounding neurons. Conversely, NO generated from eNOS is critical in 
      maintaining cerebral blood flow and reducing infarct volume. iNOS, which is not 
      normally present in healthy tissue, is induced shortly after ischemia and 
      contributes to secondary late-phase damage. CONCLUSIONS: Pharmacological and 
      genetic approaches have significantly advanced our knowledge regarding the role 
      of NO and the different NOS isoforms in focal cerebral ischemia. nNOS and iNOS 
      play key roles in neurodegeneration, while eNOS plays a prominent role in 
      maintaining cerebral blood flow and preventing neuronal injury.
FAU - Samdani, A F
AU  - Samdani AF
AD  - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, 
      MD 21287, USA.
FAU - Dawson, T M
AU  - Dawson TM
FAU - Dawson, V L
AU  - Dawson VL
LA  - eng
GR  - NS 01578/NS/NINDS NIH HHS/United States
GR  - NS 33142/NS/NINDS NIH HHS/United States
GR  - NS 33277/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*enzymology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase/*metabolism
RF  - 58
EDAT- 1997/06/01 00:00
MHDA- 1997/06/01 00:01
CRDT- 1997/06/01 00:00
PHST- 1997/06/01 00:00 [pubmed]
PHST- 1997/06/01 00:01 [medline]
PHST- 1997/06/01 00:00 [entrez]
AID - 10.1161/01.str.28.6.1283 [doi]
PST - ppublish
SO  - Stroke. 1997 Jun;28(6):1283-8. doi: 10.1161/01.str.28.6.1283.