The Role of Platelet Activation and Inflammation in Early Brain Injury Following Subarachnoid Hemorrhage.

Background: Early brain injury (EBI) following aneurysmal subarachnoid hemorrhage (SAH) is an important predictor of poor functional outcome, yet the underlying mechanism is not well understood. Animal studies suggest that platelet activation and inflammation with subsequent microthrombosis and ischemia may be a mechanism of EBI.

Methods: A prospective, hypothesis-driven study of spontaneous, SAH patients and controls was conducted.

Sexual dimorphism in gene expression after aneurysmal subarachnoid hemorrhage.

Background And Purpose: Inflammation and compromise in structure and function of cerebral parenchymal microvasculature begins early after subarachnoid hemorrhage (SAH). We recently found greater inflammation and greater vascular compromise in male than in female rats following SAH. In this study, we investigated whether this cross-sexual difference in pathology is reflected in expression levels of genes related to vascular inflammation and structural compromise.

Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice.

Stroke results in brain tissue damage from ischemia and oxidative stress. Molecular regulators of the protective versus deleterious cellular responses after cerebral ischemia remain to be identified. Here, we show that deletion of Smad1, a conserved transcription factor that mediates canonical bone morphogenetic protein (BMP) signaling, results in neuroprotection in an ischemia-reperfusion (I/R) stroke model.

The rat endovascular perforation model of subarachnoid hemorrhage.

The rat endovascular perforation model is considered the closest replica of human condition. Since its development, this model has been extensively used to study early brain injury after subarachnoid hemorrhage (SAH). However, like any other animal model, it has advantages and limitations.

Early events after aneurysmal subarachnoid hemorrhage.

The first 72 h after aneurysmal subarachnoid hemorrhage (SAH) is a critical period for the patient. Most of the deaths in the SAH patient population occur during this time, and a number of key events activate and trigger mechanisms that not only contribute to early brain injury but evolve over time and participate in the delayed complications. This review highlights the contribution of key events to the early brain injury and to overall outcome after SAH.

Rat endovascular perforation model.

Experimental animal models of aneurysmal subarachnoid hemorrhage (SAH) have provided a wealth of information on the mechanisms of brain injury. The rat endovascular perforation (EVP) model replicates the early pathophysiology of SAH and hence is frequently used to study early brain injury following SAH. This paper presents a brief review of historical development of the EVP model and details the technique used to create SAH and considerations necessary to overcome technical challenges.

Acute ischaemia after subarachnoid haemorrhage, relationship with early brain injury and impact on outcome: a prospective quantitative MRI study.

Objective: To determine if ischaemia is a mechanism of early brain injury at the time of aneurysm rupture in subarachnoid haemorrhage (SAH) and if early MRI ischaemia correlates with admission clinical status and functional outcome.

Methods: In a prospective, hypothesis-driven study patients with SAH underwent MRI within 0-3 days of ictus (prior to vasospasm) and a repeat MRI (median 7 days). The volume and number of diffusion weighted imaging (DWI) positive/apparent diffusion coefficient (ADC) dark lesions on acute MRI were quantitatively assessed.

Gender influences the initial impact of subarachnoid hemorrhage: an experimental investigation.

Aneurysmal subarachnoid hemorrhage (SAH) carries high early patient mortality. More women than men suffer from SAH and the average age of female SAH survivors is greater than that of male survivors; however, the overall mortality and neurological outcomes are not better in males despite their younger age. This pattern suggests the possibility of gender differences in the severity of initial impact and/or in subsequent pathophysiology.

Aneurysmal subarachnoid hemorrhage models: do they need a fix?

The discovery of tissue plasminogen activator to treat acute stroke is a success story of research on preventing brain injury following transient cerebral ischemia (TGI). That this discovery depended upon development of embolic animal model reiterates that proper stroke modeling is the key to develop new treatments. In contrast to TGI, despite extensive research, prevention or treatment of brain injury following aneurysmal subarachnoid hemorrhage (aSAH) has not been achieved.

Cerebral microvasculature is an early target of subarachnoid hemorrhage.

Most subarachnoid hemorrhage (SAH) patients exhibit clinical signs of cerebral ischemia at admission but no angiographic vasospasm. Consequently, the source of early cerebral ischemia is not understood. Parenchymal microvessels may contribute to early cerebral ischemia, but the low resolution of current imaging has prevented their analysis in SAH patients.

The importance of early brain injury after subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency that accounts for 5% of all stroke cases. Individuals affected are typically in the prime of their lives (mean age 50 years). Approximately 12% of patients die before receiving medical attention, 33% within 48 h and 50% within 30 days of aSAH.

Cell death starts early after subarachnoid hemorrhage.

Brain injury begins early after aneurysmal subarachnoid hemorrhage (SAH). Although cell death via apoptosis and necrosis is known to be present in brain 24 h after SAH, it is not known how soon after SAH cell death begins. We have previously described structural changes in rat brain microvessels 10 min after induction of SAH by endovascular puncture.

Reduction of neutrophil activity decreases early microvascular injury after subarachnoid haemorrhage.

Background: Subarachnoid haemorrhage (SAH) elicits rapid pathological changes in the structure and function of parenchymal vessels (≤ 100 μm). The role of neutrophils in these changes has not been determined. This study investigates the role of neutrophils in early microvascular changes after SAH METHOD: Rats were either untreated, treated with vinblastine or anti-polymorphonuclear (PMN) serum, which depletes neutrophils, or treated with pyrrolidine dithiocarbamate (PDTC), which limits neutrophil activity.

Metamorphosis of subarachnoid hemorrhage research: from delayed vasospasm to early brain injury.

Delayed vasospasm that develops 3-7 days after aneurysmal subarachnoid hemorrhage (SAH) has traditionally been considered the most important determinant of delayed ischemic injury and poor outcome. Consequently, most therapies against delayed ischemic injury are directed towards reducing the incidence of vasospasm. The clinical trials based on this strategy, however, have so far claimed limited success; the incidence of vasospasm is reduced without reduction in delayed ischemic injury or improvement in the long-term outcome.

Nitric oxide in early brain injury after subarachnoid hemorrhage.

Nitric Oxide (NO) is the major regulator of cerebral blood flow. In addition, it inhibits platelet adherence and aggregation, reduces adherence of leukocytes to the endothelium, and suppresses vessel injury. NO is produced on demand by nitric oxide synthase and has a very short half life.

Early micro vascular changes after subarachnoid hemorrhage.

During the last decade much effort has been invested in understanding the events that occur early after SAH. It is now widely accepted that these early events not only participate in the early ischemic injury but also set the stage for the pathogenesis of delayed vasospasm. That early cerebral ischemia occurs after SAH is documented in both experimental SAH and in human autopsy studies; however, angiographic evidence for vasoconstriction early after SAH is lacking and the source of early ischemic injury is therefore unclear.

Luminal platelet aggregates in functional deficits in parenchymal vessels after subarachnoid hemorrhage.

The pathophysiology of early ischemic injury after aneurysmal subarachnoid hemorrhage (SAH) is not understood. This study examined the acute effect of endovascular puncture-induced SAH on parenchymal vessel function in rat, using intravascular fluorescent tracers to assess flow and vascular permeability and immunostaining to assess structural integrity and to visualize platelet aggregates. In sham-operated animals, vessels were well filled with tracer administered 10s before sacrifice, and parenchymal escape of tracer was rare.

Adenosine A(2A) receptors in early ischemic vascular injury after subarachnoid hemorrhage. Laboratory investigation.

Object: The role of adenosine A(2A) receptors in the early vascular response after subarachnoid hemorrhage (SAH) is unknown. In other forms of cerebral ischemia both activation and inhibition of A(2A) receptors is reported to be beneficial. However, these studies mainly used pharmacological receptor modulation, and most of the agents available exhibit low specificity.

Acute cerebral vascular injury after subarachnoid hemorrhage and its prevention by administration of a nitric oxide donor.

Object: Structural changes in brain parenchymal vessels occur within minutes after subarachnoid hemorrhage (SAH). These changes include platelet aggregation, activation of vascular collagenases, and destruction of perivascular collagen IV. Because collagen IV is an important component of the basal lamina, the authors attempted to further define changes in vascular structure (length and luminal diameter) and their relationship to vascular permeability immediately after SAH.

Mechanisms of acute brain injury after subarachnoid hemorrhage.

Brain injury after subarachnoid hemorrhage (SAH) is a biphasic event with an acute ischemic insult at the time of the initial bleed and secondary events such as cerebral vasospasm 3 to 7 days later. Although much has been learned about the delayed effects of SAH, less is known about the mechanisms of acute SAH-induced injury. Distribution of blood in the subarachnoid space, elevation of intracranial pressure, reduced cerebral perfusion and cerebral blood flow (CBF) initiates the acute injury cascade.

Acute microvascular platelet aggregation after subarachnoid hemorrhage.

Object: The mechanisms underlying acute cerebral ischemia after subarachnoid hemorrhage (SAH) are not well established. Platelets aggregate within major cerebral vessels hours after SAH, but this has not been studied in the microvasculature. Platelet aggregates within the microvasculature could mechanically obstruct the lumen and initiate events that injure vessel structure.

Acute alterations in microvascular basal lamina after subarachnoid hemorrhage.

Object: Aneurysmal subarachnoid hemorrhage (SAH) causes acute and delayed ischemic brain injuries. The mechanisms of acute ischemic injury following SAH are poorly understood, although an acute increase in microvascular permeability has been noted. The integrity of cerebral microvessels is maintained in part by components of basal lamina: collagen IV, elastin, lamina, and so forth.

Nitric oxide synthase in acute alteration of nitric oxide levels after subarachnoid hemorrhage.

Objective: Subarachnoid hemorrhage (SAH) is associated with acute decreases and subsequent recovery of cerebral nitric oxide (NO) levels, but the mechanisms of these alterations are not known. In this study, we measured NO synthase (NOS) protein and kinetics to determine its involvement in the alterations of cerebral NO levels after SAH.

Methods: The endovascular rat model of SAH was used.