Application of magnetic resonance to animal models of cerebral ischemia

Hoehn, Mathias; Nicolaij, K Klaas; Franke, Claudia; Sanden, van der Bpj

doi:10.1002/jmri.1213

Cited by 128 publications

(112 citation statements)

References 165 publications

(218 reference statements)

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…Ischemia and stroke-The current state of knowledge on the use of MRS to analyze changing NAA levels in experimental ischemia in animals has been reviewed (Demougeot et al, 2004;Hoehn et al, 2001). The use of MRS in medical diagnosis of human neurological disease has also been described (Danielsen and Ross, 1999;Gillard et al, 2005;Lin et al, 2005).…”

Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,229

1,126

View full text Add to dashboard Cite

The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

show abstract

Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,229

1,126

View full text Add to dashboard Cite

show abstract

“…Figure 5a,b shows the percentage LV and the (I/ C)ADC av values, respectively, as calculated from the ADC maps. Both LV and (I/C)ADC av were calculated for the treated and untreated groups 16 6 2 h and 28 days post-occlusion and were not calculated for day 8 time point due to the pseudo normalization that occur at this time point (18,21). Of interest, for both investigated indices (Fig.…”

Section: Naa Level From 1 H-mrsimentioning

confidence: 99%

“…MRI and MR spectroscopy (MRS) are widely used for investigating, in vivo, neurological disorders in general, and ischemic stroke in particular (17)(18)(19). The versatility of the MR technique enables noninvasive studying of not only the progression of neurological pathology during longitudinal follow-up, but also the evaluation of the pathophysiologic state of the studied tissue, without the need of animal sacrificing.…”

mentioning

confidence: 99%

Late stimulation of the sphenopalatine‐ganglion in ischemic rats: Improvement in N‐acetyl‐aspartate levels and diffusion weighted imaging characteristics as seen by MR

Bar‐Shir

Shemesh

Nossin-Manor

et al. 2010

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Purpose: To assess, by MR spectroscopy (MRS) and diffusion weighted imaging (DWI), the ability of electrical stimulation of the sphenopalatine ganglion (SPG) to augment stroke recovery in transient middle cerebral artery occluded (t-MCAO) rats, when treatment is started 18 6 2 h post-occlusion. Materials and Methods: 1 H-MRS imaging ( 1 H-MRSI) and DWI were used to evaluate ischemic brain tissue after SPG stimulation in rats subjected to 2 h of t-MCAO. Rats were examined by 1 H-MRSI, DWI, and behavioral tests at 16 6 2 h, 8 days, and 28 days post-MCAO.Results: N-Acetyl-aspartate (NAA) levels of the stimulated and control rats were the same 16 6 2 h post-MCAO (0.52 6 0.03, 0.54 6 0.03). At 28 days post-occlusion, NAA levels were significantly higher in the treated group (0.60 6 0.04) compared with those of the untreated animals (0.50 6 0.04; P < 0.05). This effect was more pronounced for regions with low NAA values (0.16 6 0.03) that changed to 0.32 6 0.03 (P ¼ 0.04) for the treated group and to 0.10 6 0.03 (P ¼ 0.20) for the controls. DWI data showed better ischemic tissue condition for the treated rats, but the measured parameters showed only a trend of improvement. The MR results were corroborated by behavioral examinations. Conclusion:Our findings suggest that SPG stimulation may ameliorate MR tissue characteristics following t-MCAO even if treatment is started 18 h post-occlusion.Key Words: Sphenopalatine ganglion (SPG); middle cerebral artery occlusion (MCAO); N-acetyl aspartate (NAA); MRI; MR spectroscopy (MRS)

show abstract

“…[13][14][15][16][17] However, under such heavy ischemic stresses that lead to overt vascular disruption, changes in these MRI parameters may be derived not only from the weakened BBB itself, but also from other ischemia-affected tissue/vascular conditions including cytotoxicity, inflammation, and edema formation. 3,18,19 Therefore, overly simplified dichotomous division of stroke cases according to the presence of apparent trans-BBB leakage does not definitively identify the causative factors in the BBB disruption. In this study of the WEI in transient ischemic mouse models, we theoretically validated the CBV and WEI quantification strategy using a computer simulation of a tissue model with a wide range of physiologic variables and also investigated the relation between the in vivo BBB integrity and the degree of CBV restoration.…”

Section: Introductionmentioning

confidence: 99%

Cerebral Blood Volume Affects Blood–Brain Barrier Integrity in an Acute Transient Stroke Model

Huang

Kim

Atochin

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Insufficient vascular reserve after an ischemic stroke may induce biochemical cascades that subsequently deteriorate the blood-brain barrier (BBB) function. However, the direct relationship between poor cerebral blood volume (CBV) restoration and BBB disruption has not been examined in acute stroke. To quantify BBB integrity at acute stages of transient stroke, in particular for cases in which extravasation of the standard contrast agent (Gd-DTPA) is not observed, we adopted the water exchange index (WEI), a novel magnetic resonance image-derived parameter to estimate the water permeability across the BBB. The apparent diffusion coefficient (ADC) and R 2 relaxation rate constant were also measured for outlining the tissue abnormality, while fractional CBV and WEI were quantified for assessing vascular alterations. The significantly decreased ADC and R 2 in the ischemic cortices did not correlate with the changes in CBV or WEI. In contrast, a strong negative correlation between the ipsilesional WEI and CBV was found, in which stroke mice were clustered into two groups: (1) high WEI and low CBV and (2) normal WEI and CBV. The low CBV observed for mice with a disrupted BBB, characterized by a high WEI, indicates the importance of CBV restoration for maintaining BBB stability in acute stroke.

show abstract

Application of magnetic resonance to animal models of cerebral ischemia

Cited by 128 publications

References 165 publications

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Late stimulation of the sphenopalatine‐ganglion in ischemic rats: Improvement in N‐acetyl‐aspartate levels and diffusion weighted imaging characteristics as seen by MR

Cerebral Blood Volume Affects Blood–Brain Barrier Integrity in an Acute Transient Stroke Model

Contact Info

Product

Resources

About