De Michele Manuela, Amisano Paolo, Schiavo Oscar G, Cammisotto Vittoria, Carnevale Roberto, Forte Maurizio, Picchio Vittorio, Ciacciarelli Antonio, Berto Irene, Angeloni Ugo, Pugliese Silvia, Toni Danilo, Lorenzano Svetlana
Stroke Unit, Umberto I Hospital, Emergency Department, Sapienza University, 00185 Rome, Italy.
Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy.
Int J Mol Sci. 2024 Dec 7;25(23):13180. doi: 10.3390/ijms252313180.
Perihematomal hypoperfusion may lead to ischemic damage during intraparenchymal cerebral hemorrhage (ICH), resulting in worse prognosis. We aimed to (1) investigate the relationship between serum biomarkers related to oxidative stress and vasoactive substances and the occurrence of hypoperfusion and ischemic perihematomal lesions in ICH and (2) evaluate their correlation with the volumetric evolution of the hematoma and perihematomal edema. We enrolled 28 patients affected by ICH. Blood samples were collected at three different time points from symptom onset: T0, T1, and T2 (admission, 12-24 h, and 48-72 h, respectively), to measure endothelin-1 (ET-1), nitrites/nitrates (NO), soluble nicotinamide adenine dinucleotide 2 (NOX2)-derived peptide (sNOX2-dp), and asymmetric dimethylarginine (ADMA). Patients underwent brain MRI with perfusion study at T1 and MRI without perfusion at T2. 12 patients had ischemic perihematomal lesions at T1. A higher sNOX2-dp concentration at T0 was observed in patients with ischemic perihematomal lesions compared to those without ( = 0.051) and with a more severe perihematomal edema at T2 ( = 0.011). The ischemic perihematomal lesions development was also associated with an increased hematoma volume ( < 0.005), perilesional edema ( = 0.046), and greater midline shift ( = 0.036). ET-1 values at T1 were inversely correlated with hemorrhage volume at T2 (ρ = -0.717, = 0.030). NOX2 activation may have a role in the development of ischemic perihematomal lesions. The association between higher ET-1 values and a lower hemorrhage volume could be related to the ET-1 vasoconstriction action on the ruptured vessel wall.
脑出血周围低灌注可能在脑实质内出血（ICH）期间导致缺血性损伤，从而导致更差的预后。我们旨在：（1）研究与氧化应激和血管活性物质相关的血清生物标志物与ICH中低灌注和血肿周围缺血性病变发生之间的关系；（2）评估它们与血肿体积演变和血肿周围水肿的相关性。我们纳入了28例ICH患者。从症状发作起在三个不同时间点采集血样：T0、T1和T2（分别为入院时、12 - 24小时和48 - 72小时），以测量内皮素-1（ET-1）、亚硝酸盐/硝酸盐（NO）、可溶性烟酰胺腺嘌呤二核苷酸2（NOX2）衍生肽（sNOX2-dp）和不对称二甲基精氨酸（ADMA）。患者在T1时接受脑MRI灌注研究，在T2时接受无灌注的MRI检查。12例患者在T1时有血肿周围缺血性病变。与无缺血性血肿周围病变的患者相比，有缺血性血肿周围病变的患者在T0时sNOX2-dp浓度更高（P = 0.051），且在T2时血肿周围水肿更严重（P = 0.011）。血肿周围缺血性病变的发展还与血肿体积增加（P < 0.005）、病灶周围水肿（P = 0.046）和更大的中线移位（P = 0.036）相关。T1时的ET-1值与T2时的出血量呈负相关（ρ = -0.717，P = 0.030）。NOX2激活可能在血肿周围缺血性病变的发展中起作用。较高的ET-1值与较低的出血量之间的关联可能与ET-1对破裂血管壁的血管收缩作用有关。
