PMID- 10629768
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 850
IP  - 1-2
DP  - 1999 Dec 11
TI  - Hydroxylamine attenuates the effects of simulated subarachnoid hemorrhage in the 
      rat brain and improves neurological outcome.
PG  - 225-33
AB  - Some of the neurological deficits that emerge after aneurysmal subarachnoid 
      hemorrhage (SAH) in humans are presumably caused by ischemic brain damage 
      consequential to SAH-induced delayed cerebral vasospasm. This vasospasm probably 
      results from an imbalance among vasoactive factors released from both the clot 
      formed by extravasated blood and adjacent tissues, and in particular from a 
      decrease in the endothelium-derived relaxing factor nitric oxide (NO). Brain 
      ischemia is also known to elevate brain production and deposition of 
      beta-amyloid, and to induce a delayed increase in total NO synthase (NOS) 
      activity due to induction of expression of so-called induced NOS isoform, 
      phenomena that may secondarily contribute to SAH-related brain damage. The aim of 
      this study was to investigate the effects of treatment with the intracellular NO 
      donor hydroxylamine on: (i) basilar arterial wall that remained in a direct 
      contact with the clot, (ii) formation of the beta-amyloid precursor protein 
      (beta-APP), (iii) total brain NOS activity, and (iv) neurological outcome in a 
      'two-hemorrhage' rat SAH model. Intraperitoneal (i.p.) administration of 0.18 
      mmol/kg hydroxylamine hydrochloride (12.5 mg/kg) twice daily for 7 days beginning 
      immediately after the first 'hemorrhage' (intracisternal blood injection) reduced 
      basilar arterial wall damage and attenuated post-SAH neurological deficit. It 
      also reduced the SAH-related increases in hippocampal and cortical beta-APP 
      immunoreactivities and hippocampal NOS activity measured 24 h after commencement 
      of the treatment. These results indicate that intracellular NO donors that yield 
      NO through the action of widely distributed enzymes in brain cells (cytochromes, 
      catalase) can attenuate detrimental effects of SAH.
FAU - Ryba, M S
AU  - Ryba MS
AD  - Laboratory of Experimental Pharmacology, Polish Academy of Sciences Medical 
      Research Centre, Warsaw, Poland.
FAU - Gordon-Krajcer, W
AU  - Gordon-Krajcer W
FAU - Walski, M
AU  - Walski M
FAU - Chalimoniuk, M
AU  - Chalimoniuk M
FAU - Chrapusta, S J
AU  - Chrapusta SJ
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Nitric Oxide Donors)
RN  - 2FP81O2L9Z (Hydroxylamine)
SB  - IM
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Brain/*pathology/ultrastructure
MH  - Brain Ischemia/drug therapy/physiopathology
MH  - Cerebral Arteries/drug effects/pathology/ultrastructure
MH  - Cerebral Cortex/pathology/ultrastructure
MH  - Cerebrovascular Circulation/drug effects
MH  - Female
MH  - Hippocampus/pathology/ultrastructure
MH  - Hydroxylamine/*therapeutic use
MH  - Male
MH  - Microscopy, Electron
MH  - Nitric Oxide Donors/*therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Subarachnoid Hemorrhage/*drug therapy/pathology/physiopathology
EDAT- 2000/01/12 00:00
MHDA- 2000/01/12 00:01
CRDT- 2000/01/12 00:00
PHST- 2000/01/12 00:00 [pubmed]
PHST- 2000/01/12 00:01 [medline]
PHST- 2000/01/12 00:00 [entrez]
AID - S0006-8993(99)02161-7 [pii]
AID - 10.1016/s0006-8993(99)02161-7 [doi]
PST - ppublish
SO  - Brain Res. 1999 Dec 11;850(1-2):225-33. doi: 10.1016/s0006-8993(99)02161-7.