N-acetyl aspartate levels early after ischemic stroke accurately reflect long-term brain damage
Background: Estimation of brain damage following an ischemic stroke is most often performed within the first few days after the insult, where large amounts of oedematous fluid have accumulated. This can potentially hamper correct measurement of infarcted area, since oedema formation poorly reflects...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024002640 |
| _version_ | 1797328693481177088 |
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| author | Henrik Hasseldam Rune Skovgaard Rasmussen Henrik Hussein El Ali Flemming Fryd Johansen |
| author_facet | Henrik Hasseldam Rune Skovgaard Rasmussen Henrik Hussein El Ali Flemming Fryd Johansen |
| author_sort | Henrik Hasseldam |
| collection | DOAJ |
| description | Background: Estimation of brain damage following an ischemic stroke is most often performed within the first few days after the insult, where large amounts of oedematous fluid have accumulated. This can potentially hamper correct measurement of infarcted area, since oedema formation poorly reflects infarct size. This study presents a non-invasive, easily applicable and reliable method to accurately predict long-term evolution and late-stage infarction. Objective: We performed a longitudinal analysis of brain infarct evolution after MCAO in mice, in order to determine whether water-compensated N-Acetylaspartate (NAA) levels in the infarct area, measured 24 h after the insult, is a suitable marker for late-stage infarction and thereby prognosis. Methods: Twenty mice were divided into 4 groups and scanned longitudinally at different time-points after MCAO, followed by euthanisation for histology: Group 1) MRI/MRS at day 1 after MCAO (n = 4), Group 2) MRI/MRS at days 1 and 7 after MCAO (n = 5), Group 3) MRI/MRS at days 1, 7, and 14 after MCAO (n = 3), and Group 4) MRI/MRS at days 1, 7, 14, and 28 after MCAO (n = 4). At days 1, 7, 14, and 28, NAA levels were correlated with histological determination of neuronal death based on Nissl and H&E stainings. Results: Twenty-four hours after the insult, NAA levels in the infarcted area decreased by 35 %, but steadily returned to normal after 28 days. In the acute phases, NAA levels strongly correlated with loss of Nissl substance (r2 = −0.874, p = 0.002), whereas NAA levels in later stages reflect glial metabolism and tissue reorganisation. Most importantly, NAA levels 24 h after MCAO was highly correlated with late stage infarction at days 14 and 28 (r2 = 0.73, p = 0.01), in contrast to T2 (r2 = 0.06, p = 0.59). Conclusions: By using a fixed voxel, which is easily positioned in the affected area, it is possible to obtain reliable measures of the extent of neuronal loss at early time points independent of oedema and brain deformation. Importantly, NAA levels 24 h after MCAO accurately reflects late-stage infarction, suggesting that NAA is a useful prognostic biomarker early after an ischemic stroke. |
| first_indexed | 2024-03-08T06:56:21Z |
| format | Article |
| id | doaj.art-d63beff21a7c46f194bc0e5bd1ae23d9 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T06:56:21Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-d63beff21a7c46f194bc0e5bd1ae23d92024-02-03T06:36:40ZengElsevierHeliyon2405-84402024-01-01102e24233N-acetyl aspartate levels early after ischemic stroke accurately reflect long-term brain damageHenrik Hasseldam0Rune Skovgaard Rasmussen1Henrik Hussein El Ali2Flemming Fryd Johansen3University of Copenhagen, BRIC, 2200 Copenhagen, Denmark; Corresponding author. University of Copenhagen, BRIC, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.University of Copenhagen, BRIC, 2200 Copenhagen, DenmarkUniversity of Copenhagen, Department of Biomedical Sciences, 2200 Copenhagen, DenmarkUniversity of Copenhagen, BRIC, 2200 Copenhagen, DenmarkBackground: Estimation of brain damage following an ischemic stroke is most often performed within the first few days after the insult, where large amounts of oedematous fluid have accumulated. This can potentially hamper correct measurement of infarcted area, since oedema formation poorly reflects infarct size. This study presents a non-invasive, easily applicable and reliable method to accurately predict long-term evolution and late-stage infarction. Objective: We performed a longitudinal analysis of brain infarct evolution after MCAO in mice, in order to determine whether water-compensated N-Acetylaspartate (NAA) levels in the infarct area, measured 24 h after the insult, is a suitable marker for late-stage infarction and thereby prognosis. Methods: Twenty mice were divided into 4 groups and scanned longitudinally at different time-points after MCAO, followed by euthanisation for histology: Group 1) MRI/MRS at day 1 after MCAO (n = 4), Group 2) MRI/MRS at days 1 and 7 after MCAO (n = 5), Group 3) MRI/MRS at days 1, 7, and 14 after MCAO (n = 3), and Group 4) MRI/MRS at days 1, 7, 14, and 28 after MCAO (n = 4). At days 1, 7, 14, and 28, NAA levels were correlated with histological determination of neuronal death based on Nissl and H&E stainings. Results: Twenty-four hours after the insult, NAA levels in the infarcted area decreased by 35 %, but steadily returned to normal after 28 days. In the acute phases, NAA levels strongly correlated with loss of Nissl substance (r2 = −0.874, p = 0.002), whereas NAA levels in later stages reflect glial metabolism and tissue reorganisation. Most importantly, NAA levels 24 h after MCAO was highly correlated with late stage infarction at days 14 and 28 (r2 = 0.73, p = 0.01), in contrast to T2 (r2 = 0.06, p = 0.59). Conclusions: By using a fixed voxel, which is easily positioned in the affected area, it is possible to obtain reliable measures of the extent of neuronal loss at early time points independent of oedema and brain deformation. Importantly, NAA levels 24 h after MCAO accurately reflects late-stage infarction, suggesting that NAA is a useful prognostic biomarker early after an ischemic stroke.http://www.sciencedirect.com/science/article/pii/S2405844024002640MCAOMRINAAPrognostic markerinfarct maturation |
| spellingShingle | Henrik Hasseldam Rune Skovgaard Rasmussen Henrik Hussein El Ali Flemming Fryd Johansen N-acetyl aspartate levels early after ischemic stroke accurately reflect long-term brain damage Heliyon MCAO MRI NAA Prognostic marker infarct maturation |
| title | N-acetyl aspartate levels early after ischemic stroke accurately reflect long-term brain damage |
| title_full | N-acetyl aspartate levels early after ischemic stroke accurately reflect long-term brain damage |
| title_fullStr | N-acetyl aspartate levels early after ischemic stroke accurately reflect long-term brain damage |
| title_full_unstemmed | N-acetyl aspartate levels early after ischemic stroke accurately reflect long-term brain damage |
| title_short | N-acetyl aspartate levels early after ischemic stroke accurately reflect long-term brain damage |
| title_sort | n acetyl aspartate levels early after ischemic stroke accurately reflect long term brain damage |
| topic | MCAO MRI NAA Prognostic marker infarct maturation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024002640 |
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