scholarly journals Changes in N-Acetyl-Aspartate Content during Focal and Global Brain Ischemia of the Rat

1995 ◽  
Vol 15 (4) ◽  
pp. 639-646 ◽  
Author(s):  
Thomas Nikolaj Sager ◽  
Henning Laursen ◽  
Anker Jon Hansen
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Brain Ischemia ◽  
Focal Ischemia ◽  
Artery Occlusion ◽  
Global Ischemia ◽  
Global Brain Ischemia ◽  
Global Brain ◽  
Cerebral Artery Occlusion

N-Acetyl-aspartate (NAA) is almost exclusively localized in neurons in the mature brain and might be used as a neuronal marker. It has been reported that the NAA content in human brain is decreased in neurodegenerative diseases and in stroke. Since the NAA content can be determined by nuclear magnetic resonance techniques, it has potential as a diagnostic and prognostic marker. The objective of this study was to examine the change of NAA content and related substances following cerebral ischemia and compare the results to the damage of the tissue. We used rats to study the changes of NAA, N-acetyl-aspartyl-glutamate (NAAG), glutamate, and aspartate contents over a time course of 24 h in brain regions affected by either permanent middle cerebral artery occlusion (focal ischemia) or decapitation (global ischemia). The decreases of NAA and NAAG contents following global brain ischemia were linear over time but significant only after 4 and 2 h, respectively. After 24 h, the levels of NAA and NAAG were 24 and 44% of control values, respectively. The concentration of glutamate did not change, whereas the aspartate content increased at a rate comparable with the rate of decrease of NAA content. This is consistent with NAA being preferentially degraded by the enzyme amidohydrolase II in global ischemia. In focal ischemia, there was a rapid decline of NAA within the first 8 h of ischemia followed by a slower rate of reduction. The reductions of NAA and NAAG contents in focal ischemia were significant after 4 and 24 h, respectively. After 24 h, the NAA and NAAG contents were 33 and 64% of control values, respectively. Also, the glutamate and aspartate contents exhibited significant decreases in focal ischemic tissue. Our studies show that NAA decreases during brain ischemia, the initial rate being faster in focal ischemia than in global ischemia. In rat transient focal ischemia, others have shown that a middle cerebral artery occlusion of 2- to 3-h duration is sufficient to produce an infarct that is similar in size to that following permanent occlusion for 24 h. The fact that we observed only a 10% decrease of NAA content 2 h after occlusion demonstrates that the NAA content of the tissue does not reflect neuronal viability. Thus, the incompetence with which ischemic/infarcted tissue removes NAA will lead to overestimation of the number of viable neurons in acute situations. Only when steady state prevails may [NAA] be used as a marker of viable nerve cells.

scholarly journals Endothelin Levels Increase in Rat Focal and Global Ischemia

1994 ◽  
Vol 14 (2) ◽  
pp. 337-342 ◽  
Author(s):  
F. C. Barone ◽  
M. Y.-T. Globus ◽  
W. J. Price ◽  
R. F. White ◽  
B. L. Storer ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Vascular Function ◽  
Tissue Injury ◽  
Extracellular Fluid ◽  
Artery Occlusion ◽  
Global Ischemia ◽  
Vessel Occlusion ◽  
Cerebral Artery Occlusion

Endothelin-1, a peptide exhibiting extremely potent cerebral vasoactive properties, is elevated in the cerebrospinal fluid after hemorrhagic stroke and implicated in cerebral vasospasm. The purpose of this study was to determine changes in endothelin in ischemic rat brain by assaying endothelin tissue and extracellular levels. Immunoreactive endothelin levels in ischemic brain tissue following permanent or transient focal ischemia produced by middle cerebral artery occlusion was determined. In addition, endothelin levels were assayed in striatal extracellular fluid collected by microdialysis before, during, and after global ischemia produced by two-vessel occlusion combined with hypotension. Twenty-four hours after the onset of permanent middle cerebral artery occlusion, the ischemic cortex level (0.58 ± 0.27 fmol/mg protein) of immunoreactive endothelin was significantly (p < 0.05) increased, by 100%, over that in the nonischemic cortex (0.29 ± 0.13 fmol/mg protein). Transient artery occlusion for 80 min with reperfusion for 24 h also resulted in a similar significant (p < 0.05) increase, 78%, in immunoreactive endothelin in the ischemic zone. Global forebrain ischemia significantly (p < 0.05) increased the level of immunoreactive endothelin collected in striatal microdialysis perfusate, from a basal level of 14.6 ± 6.7 to 26.5 ± 7.7 and 26.2 ± 7.4 amol/μl (i.e. 82 and 79%). These changes reflect the relative picomolar extracellular concentration increases during ischemia and following reperfusion, respectively. This is the first demonstration of elevated levels of endothelin in focal ischemic tissue and in the extracellular fluid in global ischemia and suggests a role of the peptide in ischemic and postischemic derangements of cerebral vascular function and tissue injury.

scholarly journals Transient Focal Ischemia Induces Extensive Temporal Changes in Rat Cerebral MicroRNAome

2009 ◽  
Vol 29 (4) ◽  
pp. 675-687 ◽  
Author(s):  
Ashuthosh Dharap ◽  
Kellie Bowen ◽  
Robert Place ◽  
Long-Cheng Li ◽  
Raghu Vemuganti
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Noncoding Rna ◽  
Critical Role ◽  
In Silico Analysis ◽  
Focal Ischemia ◽  
Artery Occlusion ◽  
Mirna Biogenesis ◽  
Cerebral Artery Occlusion

MicroRNAs (miRNAs) are ∼22 nucleotides long, noncoding RNAs that control cellular function by either degrading mRNAs or arresting their translation. To understand their functional significance in ischemic pathophysiology, we profiled miRNAs in adult rat brain as a function of reperfusion time after transient middle cerebral artery occlusion. Of the 238 miRNAs evaluated, 8 showed increased and 12 showed decreased expression at least at 4 out of 5 reperfusion time points studied between 3 h and 3 days compared with sham. Of those, 17 showed > 5 fold change. Bioinformatics analysis indicated a correlation between miRNAs altered to several mRNAs known to mediate inflammation, transcription, neuroprotection, receptors function, and ionic homeostasis. Antagomir-mediated prevention of mir-145 expression led to an increased protein expression of its downstream target superoxide dismutase-2 in the postischemic brain. In silico analysis showed sequence complementarity of eight miRNAs induced after focal ischemia to 877 promoters indicating the possibility of noncoding RNA-induced activation of gene expression. The mRNA expression of the RNases Drosha and Dicer, cofactor Pasha, and the pre-miRNA transporter exportin-5, which modulate miRNA biogenesis, were not altered after transient middle cerebral artery occlusion. Thus, the present studies indicate a critical role of miRNAs in controlling mRNA transcription and translation in the postischemic brain.

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