The Role of Microclot Formation in an Acute Subarachnoid Hemorrhage Model in the Rabbit

Abstract

Background. Microvascular dysfunction and microthrombi formation are believed to contribute to development of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH). Objective. This study aimed to determine (i) extent of microthrombus formation and neuronal apoptosis in the brain parenchyma using a blood shunt SAH model in rabbits; (ii) correlation of structural changes in microvessels with EBI characteristics. Methods. Acute SAH was induced using a rabbit shunt cisterna magna model. Extent of microthrombosis was detected 24 h post-SAH (n = 8) by fibrinogen immunostaining, compared to controls (n = 4). We assessed apoptosis by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) in cortex and hippocampus. Results. Our results showed significantly more TUNEL-positive cells (SAH: 115 ± 13; controls: 58 ± 10; P = 0.016) and fibrinogen-positive microthromboemboli (SAH: 9 ± 2; controls: 2 ± 1; P = 0.03) in the hippocampus after aneurysmal SAH. Conclusions. We found clear evidence of early microclot formation in a rabbit model of acute SAH. The extent of microthrombosis did not correlate with early apoptosis or CPP depletion after SAH; however, the total number of TUNEL positive cells in the cortex and the hippocampus significantly correlated with mean CPP reduction during the phase of maximum depletion after SAH induction. Both microthrombosis and neuronal apoptosis may contribute to EBI and subsequent DCI.

The Rabbit Shunt Model of Subarachnoid Haemorrhage

“…The anatomy, adhesions in the subarachnoid space and cerebroventricular system in rabbits are largely different from that of humans [44]. During acute blood shunt-induced SAH [31,45,32]. Unpublished data of recent experimental studies suggest that there is no correlation between increase in ICP and amount of blood distributed in the subarachnoid space.…”

“…These severe pathophysiological disturbances and their subsequent consequences cause early microclot formation, significant damage to the hippocampus, basal cortex and cerebral vasculature 24 h after shunt-induced SAH and triggers marked basilar artery vasoconstriction 72 h after initial bleeding [45,32,31]. Pathophysiological events caused by shunt-induced SAH are summarised in Table 2 and Fig.…”

Predictive value of plasma fibrinogen levels for outcome of aneurysmal subarachnoid haemorrhage during the first week of illness

“…Platelet aggregates are found in the major cerebral arteries within two hours of experimental SAH [35]. The elevation of fibrinogen might represent microclot formation within 24 h after SAH [36]. This might be one reason for the beneficial effect of nimodipine [37], which may improve recovery from ischaemia by increasing fibrinolytic activity [38].…”

The Role of Sartans in the Treatment of Stroke and Subarachnoid Hemorrhage: A Narrative Review of Preclinical and Clinical Studies

“…LS, an already well-established antihypertensive drug in daily clinical practice and well examined in preclinical and clinical settings of ischemic stroke, shows promising results by attenuating cerebral inflammation and restoring cerebral autoregulation [64,105,[122][123][124][125]. Facing preclinical aSAH research, beneficial effects of Sartans have been shown.…”