Ultra-Early Cerebral Thrombosis Formation After Experimental Subarachnoid Hemorrhage Detected on T2* Magnetic Resonance Imaging

Abstract

Background and Purpose: The mechanisms of brain damage during ultra-early subarachnoid hemorrhage (SAH) have not been well studied. The current study examined the SAH-induced hyperacute brain damage at 4 hours using magnetic resonance imaging and brain histology in a mouse model. Methods: SAH was induced by endovascular perforation in adult mice. First, adult male wild-type mice underwent magnetic resonance imaging T2 and T2* 4 hours after an endovascular perforation or a sham operation and were euthanized to assess brain histology. Second, male and female adult lipocalin-2 knockout mice had SAH. All animals underwent magnetic resonance imaging at 4 hours, and the brains were harvested for brain histology. Results: T2* hypointensity vessels were observed in the brain 4 hours after SAH in male wild-type mice. The numbers of T2*-positive vessels were significantly higher in SAH brains than in sham-operated mice. Brain histology showed thrombosis and erythrocyte plugs in the T2*-positive cerebral vessels which may be venules. The number of T2*-positive vessels correlated with SAH grade and the presence of T2 lesions. Brain thrombosis was also accompanied by albumin leakage and neuronal injury. LCN2 deficient male mice had lower numbers of T2*-positive vessels after SAH compared with wild-type male mice. Conclusions: SAH causes ultra-early brain vessel thrombosis that can be detected by T2* gradient-echo sequence at 4 hours after SAH. LCN2 deficiency decreased the number of T2*-positive vessels.

Cerebrospinal fluid hemoglobin drives subarachnoid hemorrhage-related secondary brain injury

“…For instance, recent studies indicate that microthrombi formation after aSAH contributes to the development of DCI and DIND. 47 , 48 CSF-Hb might be also involved in this, as endothelial NO scavenging by Hb has been shown to disinhibit platelet adhesion and aggregation. 49 – 51 In addition, there may be an indirect link to Hb-induced microvasospasms, 15 , 17 , 52 – 56 promoting the formation of microthrombi by resulting mechanical endothelial damage.…”

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage

“…In terms of the mechanisms for microcirculatory impairments, previous clinical and experimental studies revealed that microthrombosis and microvasospasm occurred during both the ultra-early and the subacute phase. 13,15,16,41,[53][54][55][56][57][58] Microthrombosis can be induced by systemic hypercoagulability, increased plateletactivation, endothelial cell damage, and microcirculatory stasis. [13][14][15][16][53][54][55][56][57][58][59][60][61][62][63] Microthrombosis can be induced by systemic hypercoagulability, increased plateletactivation, endothelial cell damage, and microcirculatory stasis.…”

“…DCI was defined as clinical deterioration of more than two points on the Glasgow Coma Scale (GCS), the development of new, focal neurological signs, or both, when the cause was felt to be ischemia attributable to vasospasm after other possible causes of worsening had been excluded. 41 All cerebral angiography was performed by flat panel DSA (AXIOM-Artiszee V R , Siemens Health Care). Using standard angiographic methods (transfemoral route) for all patients, image acquisition was performed via a 4 Fr catheter with the tip positioned at the C3-4 level.…”

Antiplatelet therapy for standalone coiling of ruptured intracranial aneurysms: a systematic review and meta-analysis

“…In the systemic system after aSAH, more specifically, activated platelet is associated with neuroinflammation, while the role is not yet fully understood 29 30. In CNS, recent studies found that ultra-early cerebral microthrombi that develop a few hours after experimental aSAH are likely due to inflammatory activation 31 32. Excessive inflammatory stimuli and mechanical forces that can be caused by endovascular procedures could result in pathological perturbation, impairing the normal activity of vascular endothelial cells and accelerating focal coagulation responses 33.…”