Translational stroke research
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Brain arteriovenous malformations (AVMs) are abnormal connections of arteries and veins, resulting in arteriovenous shunting of blood. Primary medical therapy is lacking; treatment options include surgery, radiosurgery, and embolization, often in combination. Judicious selection of AVM patients for treatment requires balancing risk of treatment complications against the risk of hemorrhage in the natural history course. This review focuses on the epidemiology, hemorrhage risk, and factors influencing risk of hemorrhage in the untreated natural course associated with sporadic brain AVM.
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Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. ⋯ Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.
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Transmigration of peripheral leukocytes to the brain is a major contributor to cerebral ischemic cell death mechanisms. Humanized partial major histocompatibility complex class II constructs (pMHC), covalently linked to myelin peptides, are effective for treating experimental stroke in males, but new evidence suggests that some inflammatory cell death mechanisms after brain injury are sex-specific. We here demonstrate that treatment with pMHC constructs also improves outcomes in female mice with middle cerebral artery occlusion (MCAO). ⋯ The number of calls was reduced in injured animals relative to pre-MCAO baseline regardless of RTL1000 treatment status. However, call duration was significantly improved by RTL1000 treatment, suggesting benefit to the animal's recovery of vocalization capability. We conclude that both the parent RTL1000 molecule and the novel non-polymorphic DRα1-MOG-35-55 construct were highly effective immunotherapies for treatment of transient cerebral ischemia in females.
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Systemic lupus erythematosus (SLE) is an autoimmune disease associated with significant morbidity, including premature cardiovascular disease, and mortality. Platelets bearing complement protein C4d (P-C4d) were initially determined to be specific for diagnosis of SLE and were later found to be associated with acute ischemic stroke in non-SLE patients. P-C4d may identify a subset of SLE patients with a worse clinical prognosis. ⋯ Specifically, P-C4d was associated with ischemic stroke (odds ratio 4.54, 95% CI 1.63-12.69, p = 0.004) after adjusting for age, ethnicity, and antiphospholipid antibodies. Platelet-C4d is associated with all-cause mortality and stroke in SLE patients. P-C4d may be a prognostic biomarker as well as a pathogenic clue that links platelets, complement activation, and thrombosis.
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Review
Smooth muscle phenotype switching in blast traumatic brain injury-induced cerebral vasospasm.
Due to increased survival rates among soldiers exposed to explosive blasts, blast-induced traumatic brain injury (bTBI) has become much more prevalent in recent years. Cerebral vasospasm (CVS) is a common manifestation of brain injury whose incidence is significantly increased in bTBI. CVS is characterized by initial vascular smooth muscle cell (VSMC) hypercontractility, followed by prolonged vessel remodeling and lumen occlusion, and is traditionally associated with subarachnoid hemorrhage (SAH), but recent results suggest that mechanical injury during bTBI can cause mechanotransduced VSMC hypercontractility and phenotype switching necessary for CVS development, even in the absence of SAH. Here, we review the mechanisms by which mechanical stimulation and SAH can synergistically drive CVS progression, complicating treatment options in bTBI patients.