Microvascular platelet aggregation and thrombosis after subarachnoid hemorrhage: A review and synthesis.
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ABSTRACT:
SUBMITTER: Clarke JV
PROVIDER: S-EPMC7370365 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Endovascular techniques have proven beneficial in the treatment of aneurysmal subarachnoid hemorrhage (aSAH), but with high risk of arterial clotting, emboli and dissection. Platelet activation and alterations in hemostasis may contribute to these complications. We investigated platelet activation and aggregation pathways in aSAH patients who underwent endovascular treatment.Two blood samples were taken, in the early days after bleeding and during the period at risk of vasospasm. We studied platelet activation through the expression of GpIIbIIIa and P-selectin as well as aggregation rate in the presence of agonists. Platelets from aSAH patients were compared with those from orthopedic postoperative patients (POSTOP).Platelets in aSAH were initially spontaneously activated and remained so over time. aSAH platelets were further activated with rapid aggregation in the presence of agonists, particularly ADP, with behavior comparable to POSTOP platelets.aSAH platelets showed prolonged increases in activation and aggregation. Therapies targeting the ADP pathway might reduce the risk of clotting and ischemic events in this context among patients requiring multiple endovascular procedures.Not applicable.
| S-EPMC5924502 | biostudies-literature
Project description:Subarachnoid hemorrhage (SAH) is a devastating cerebral event caused by an aneurysmal rupture. In addition to neurological injury, SAH has significant effects on cardiac function and the peripheral microcirculation. Since these peripheral complications may exacerbate brain injury, the prevention and management of these peripheral effects are important for improving the overall clinical outcome after SAH. In this investigation, we examined the effects of SAH on cardiac function and vascular reactivity in a well-characterized blood injection model of SAH. Standard echocardiographic and blood pressure measurement procedures were utilized to assess cardiac function and hemodynamic parameters in vivo; we utilized a pressure myography approach to assess vascular reactivity in cremaster skeletal muscle resistance arteries ex vivo. We observed that elevated catecholamine levels in SAH stun the myocardium, reduce cardiac output and augment myogenic vasoconstriction in isolated cremaster arteries. These cardiac and vascular effects are driven by beta- and alpha-adrenergic receptor signaling, respectively. Clinically utilized adrenergic receptor antagonists can prevent cardiac injury and normalize vascular function. We found that tumor necrosis factor (TNF) gene deletion prevents the augmentation of myogenic reactivity in SAH: since membrane-bound TNF serves as a mechanosensor in the arteries assessed, alpha-adrenergic signaling putatively augments myogenic vasoconstriction by enhancing mechanosensor activity.
| S-EPMC7237757 | biostudies-literature
Project description:Background and purposeCircadian rhythms influence the extent of brain injury following subarachnoid hemorrhage (SAH), but the mechanism is unknown. We hypothesized that cerebrovascular myogenic reactivity is rhythmic and explains the circadian variation in SAH-induced injury.MethodsSAH was modeled in mice with prechiasmatic blood injection. Inducible, smooth muscle cell-specific Bmal1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1) gene deletion (smooth muscle-specific Bmal1 1 knockout [sm-Bmal1 KO]) disrupted circadian rhythms within the cerebral microcirculation. Olfactory cerebral resistance arteries were functionally assessed by pressure myography in vitro; these functional assessments were related to polymerase chain reaction/Western blot data, brain histology (Fluoro-Jade/activated caspase-3), and neurobehavioral assessments (modified Garcia scores).ResultsCerebrovascular myogenic vasoconstriction is rhythmic, with a peak and trough at Zeitgeber times 23 and 11 (ZT23 and ZT11), respectively. Histological and neurobehavioral assessments demonstrate that higher injury levels occur when SAH is induced at ZT23, compared with ZT11. In sm-Bmal1 KO mice, myogenic reactivity is not rhythmic. Interestingly, myogenic tone is higher at ZT11 versus ZT23 in sm-Bmal1 KO mice; accordingly, SAH-induced injury in sm-Bmal1 KO mice is more severe when SAH is induced at ZT11 compared to ZT23. We examined several myogenic signaling components and found that CFTR (cystic fibrosis transmembrane conductance regulator) expression is rhythmic in cerebral arteries. Pharmacologically stabilizing CFTR expression in vivo (3 mg/kg lumacaftor for 2 days) eliminates the rhythmicity in myogenic reactivity and abolishes the circadian variation in SAH-induced neurological injury.ConclusionsCerebrovascular myogenic reactivity is rhythmic. The level of myogenic tone at the time of SAH ictus is a key factor influencing the extent of injury. Circadian oscillations in cerebrovascular CFTR expression appear to underlie the cerebrovascular myogenic reactivity rhythm.
| S-EPMC8700310 | biostudies-literature
Project description:Sixty-nine million people have a traumatic brain injury (TBI) each year, and TBI is the most common cause of subarachnoid hemorrhage (SAH). Traumatic SAH (TSAH) has been described as an adverse prognostic factor leading to progressive neurological deterioration and increased morbidity and mortality. A limited number of studies, however, evaluate recent trends in the diagnosis and management of SAH in the context of trauma. The objective of this scoping review was to understand the extent and type of evidence concerning the diagnostic criteria and management of TSAH. This scoping review was conducted following the Joanna Briggs Institute methodology for scoping reviews. The review included adults with SAH secondary to trauma, where isolated TSAH (iTSAH) refers to the presence of SAH in the absence of any other traumatic radiographic intracranial pathology, and TSAH refers to the presence of SAH with the possibility or presence of additional traumatic radiographic intracranial pathology. Data extracted from each study included study aim, country, methodology, population characteristics, outcome measures, a summary of findings, and future directives. Thirty studies met inclusion criteria. Studies were grouped into five categories by topic: TSAH associated with mild TBI (mTBI), n = 13), and severe TBI (n = 3); clinical management and diagnosis (n = 9); imaging (n = 3); and aneurysmal TSAH (n = 1). Of the 30 studies, two came from a low- and middle-income country (LMIC), excluding China, nearly a high-income country. Patients with TSAH associated with mTBI have a very low risk of clinical deterioration and surgical intervention and should be treated conservatively when considering intensive care unit admission. The Helsinki and Stockholm computed tomography scoring systems, in addition to the American Injury Scale, creatinine level, age decision tree, may be valuable tools to use when predicting outcome and death.
| S-EPMC8785754 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Depression is common and debilitating illness accompanying many neurological disorders including non-traumatic subarachnoid hemorrhage (SAH). The aim of this systematic review was to identify and critically appraise all published studies that have reported the frequency, severity and time course of depression after SAH, the factors associated with its development and the impact of depression on patients' quality of life after SAH. METHODS:The PubMed database was searched for studies published in English that recruited at least 40 patients (>18 years old) after SAH who were also diagnosed with depression. RESULTS:Altogether 55 studies covering 6,327 patients met study entry criteria. The frequency of depression ranged from 0% to 61.7%, with a weighted proportion of 28.1%. Depression remained common even several years after the index SAH. Depression after SAH was associated with female sex, premorbid depression, anxiety, substance use disorders or any psychiatric disorders, and coping styles. Comorbid cognitive impairment, fatigue, and physical disability also increased the risk of depression. Aneurysmal SAH and infarction may be related to depression as well. Depression reduces the quality of life and life satisfaction in patients after SAH. CONCLUSIONS:Depression is common after SAH and seems to persist. Further research is needed to clarify its time course and identify the neuroendocrine and neurochemical factors and brain circuits associated with the development of post-SAH depression. Randomized controlled treatment trials targeting SAH-related depression are warranted.
| S-EPMC7005349 | biostudies-literature
Project description:As the number of obese people is globally increasing, reports about the putative protective effect of obesity in life-threatening diseases, such as subarachnoid hemorrhage (SAH), are gaining more interest. This theory-the obesity paradox-is challenging to study, and the impact of obesity has remained unclear in survival of several critical illnesses, including SAH. Thus, we performed a systematic review to clarify the relation of obesity and SAH mortality. Our study protocol included systematic literature search in PubMed, Scopus, and Cochrane library databases, whereas risk-of-bias estimation and quality of each selected study were evaluated by the Critical Appraisal Skills Program and Cochrane Collaboration guidelines. A directional power analysis was performed to estimate sufficient sample size for significant results. From 176 reviewed studies, six fulfilled our eligibility criteria for qualitative analysis. One study found paradoxical effect (odds ratio, OR = 0.83 (0.74-0.92)) between morbid obesity (body mass index (BMI) > 40) and in-hospital SAH mortality, and another study found the effect between continuously increasing BMI and both short-term (OR = 0.90 (0.82-0.99)) and long-term SAH mortalities (OR = 0.92 (0.85-0.98)). However, according to our quality assessment, methodological shortcomings expose all reviewed studies to a high-risk-of-bias. Even though two studies suggest that obesity may protect SAH patients from death in the acute phase, all reviewed studies suffered from methodological shortcomings that have been typical in the research field of obesity paradox. Therefore, no definite conclusions could be drawn.
| S-EPMC7680302 | biostudies-literature
Project description:Background and purposeThe 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.MethodsSAH 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.ResultsT2* 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.ConclusionsSAH 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.
| S-EPMC7902437 | biostudies-literature
Project description:Aneurysmal subarachnoid hemorrhage (SAH) is a worldwide health burden with high fatality and permanent disability rates. The overall prognosis depends on the volume of the initial bleed, rebleeding, and degree of delayed cerebral ischemia (DCI). Cardiac manifestations and neurogenic pulmonary edema indicate the severity of SAH. The International Subarachnoid Aneurysm Trial (ISAT) reported a favorable neurological outcome with the endovascular coiling procedure compared with surgical clipping at the end of 1 year. The ISAT trial recruits were primarily neurologically good grade patients with smaller anterior circulation aneurysms, and therefore the results cannot be reliably extrapolated to larger aneurysms, posterior circulation aneurysms, patients presenting with complex aneurysm morphology, and poor neurological grades. The role of hypothermia is not proven to be neuroprotective according to a large randomized controlled trial, Intraoperative Hypothermia for Aneurysms Surgery Trial (IHAST II), which recruited patients with good neurological grades. Patients in this trial were subjected to slow cooling and inadequate cooling time and were rewarmed rapidly. This methodology would have reduced the beneficial effects of hypothermia. Adenosine is found to be beneficial for transient induced hypotension in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. The neurological benefit of pharmacological neuroprotection and neuromonitoring is not proven in patients undergoing clipping of aneurysms. DCI is an important cause of morbidity and mortality following SAH, and the pathophysiology is likely multifactorial and not yet understood. At present, oral nimodipine has an established role in the management of DCI, along with maintenance of euvolemia and induced hypertension. Following SAH, hypernatremia, although less common than hyponatremia, is a predictor of poor neurological outcome.
| S-EPMC4463029 | biostudies-other
Project description:Interleukin 6 (IL-6) is a prominent proinflammatory cytokine. Neuroinflammation in general, and IL-6 signaling in particular, appear to play a major role in the pathobiology and pathophysiology of aneurysm formation and aneurysmal subarachnoid hemorrhage (SAH). Most importantly, elevated IL-6 CSF (rather than serum) levels appear to correlate with delayed cerebral ischemia (DCI, "vasospasm") and secondary ("vasospastic") infarctions. IL-6 CSF levels may also reflect other forms of injury to the brain following SAH, i.e., early brain damage and septic complications of SAH and aneurysm treatment. This would explain why many researchers have found an association between IL-6 levels and patient outcomes. These findings clearly suggest CSF IL-6 as a candidate biomarker in SAH patients. However, at this point, discrepant findings in variable study settings, as well as timing and other issues, e.g., defining proper clinical endpoints (i.e., secondary clinical deterioration vs. angiographic vasospasm vs. secondary vasospastic infarct) do not allow for its routine use. It is also tempting to speculate about potential therapeutic measures targeting elevated IL-6 CSF levels and neuroinflammation in SAH patients. Corticosteroids and anti-platelet drugs are indeed used in many SAH cases (not necessarily with the intention to interfere with detrimental inflammatory signaling), however, no convincing benefit has been demonstrated yet. The lack of a robust clinical perspective against the background of a relatively large body of data linking IL-6 and neuroinflammation with the pathophysiology of SAH is somewhat disappointing. One underlying reason might be that most relevant studies only report correlative data. The specific molecular pathways behind elevated IL-6 levels in SAH patients and their various interactions still remain to be delineated. We are optimistic that future research in this field will result in a better understanding of the role of neuroinflammation in the pathophysiology of SAH, which in turn, will translate into the identification of suitable biomarkers and even potential therapeutic targets.
| S-EPMC8073154 | biostudies-literature
Project description:Background and objectiveAstrocytes play an important role in healthy brain function, including the development and maintenance of blood-brain barrier (BBB), structural support, brain homeostasis, neurovascular coupling and secretion of neuroprotective factors. Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH) including neuroinflammation, glutamate toxicity, brain edema, vasospasm, BBB disruption, cortical spreading depolarization (SD).MethodsWe searched PubMed up to 31 May, 2022 and evaluated the articles for screening and inclusion for subsequent systemic review. We found 198 articles with the searched terms. After exclusion based on the selection criteria, we selected 30 articles to start the systemic review.Key content and findingsWe summarized the response of astrocytes induced by SAH. Astrocytes are critical for brain edema formation, BBB reconstruction and neuroprotection in the acute stage of SAH. Astrocytes clear extracellular glutamate by increasing the uptake of glutamate and Na+/K+ ATPase activity after SAH. Neurotrophic factors released by astrocytes contribute to neurological recovery after SAH. Meanwhile, Astrocytes also form glial scars which hinder axon regeneration, produce proinflammatory cytokines, free radicals, and neurotoxic molecules.ConclusionsPreclinical studies showed that therapeutic targeting the astrocytes response could have a beneficial effect in ameliorating neuronal injury and cognitive impairment after SAH. Clinical trials and preclinical animal studies are still urgently needed in order to determine where astrocytes stand in various pathway of brain damage and repair after SAH and, above all, to develop therapeutic approaches which benefit patient outcomes.
| S-EPMC10170286 | biostudies-literature