Hasseldam Henrik, Rasmussen Rune Skovgaard, El Ali Henrik Hussein, Johansen Flemming Fryd
University of Copenhagen, BRIC, 2200 Copenhagen, Denmark.
University of Copenhagen, Department of Biomedical Sciences, 2200 Copenhagen, Denmark.
Heliyon. 2024 Jan 6;10(2):e24233. doi: 10.1016/j.heliyon.2024.e24233. eCollection 2024 Jan 30.
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.
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.
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.
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 (r = -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 (r = 0.73, p = 0.01), in contrast to T2 (r = 0.06, p = 0.59).
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.
缺血性中风后脑损伤的评估通常在损伤后的头几天内进行，此时会积聚大量水肿液。这可能会妨碍对梗死面积的正确测量，因为水肿形成并不能很好地反映梗死大小。本研究提出了一种非侵入性、易于应用且可靠的方法，以准确预测长期演变和晚期梗死。
我们对小鼠大脑中动脉闭塞（MCAO）后脑梗死的演变进行了纵向分析，以确定损伤后24小时测量的梗死区域水补偿N-乙酰天门冬氨酸（NAA）水平是否是晚期梗死及预后的合适标志物。
将20只小鼠分为4组，并在MCAO后的不同时间点进行纵向扫描，随后安乐死进行组织学检查：第1组）MCAO后第1天进行MRI/MRS检查（n = 4），第2组）MCAO后第1天和第7天进行MRI/MRS检查（n = 5），第3组）MCAO后第1天、第7天和第14天进行MRI/MRS检查（n = 3），第4组）MCAO后第1天、第7天、第14天和第28天进行MRI/MRS检查（n = 4）。在第1天、第7天、第14天和第28天，基于尼氏染色和苏木精-伊红染色，将NAA水平与神经元死亡的组织学测定相关联。
损伤后24小时，梗死区域的NAA水平下降了35%，但在28天后稳步恢复正常。在急性期，NAA水平与尼氏物质的丧失密切相关（r = -0.874，p = 0.002），而后期的NAA水平反映了胶质细胞代谢和组织重组。最重要的是，与T2（r = 0.06，p = 0.59）相比，MCAO后24小时的NAA水平与第14天和第28天的晚期梗死高度相关（r = 0.73，p = 0.01）。
通过使用易于定位在受影响区域的固定体素，可以在早期时间点获得独立于水肿和脑变形的神经元损失程度的可靠测量值。重要的是，MCAO后24小时的NAA水平准确反映了晚期梗死，表明NAA是缺血性中风后早期有用的预后生物标志物。
