Hemorrhagic Transformation in Ischemic Stroke and the Role of Inflammation

Spronk, Elena; Sykes, Gina; Falcione, Sarina; Munsterman, Danielle; Joy, Twinkle; Kamtchum‐Tatuene, Joseph; Jickling, Glen C.

doi:10.3389/fneur.2021.661955

Cited by 114 publications

(103 citation statements)

References 137 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The sodium-potassium ATP pumps are disrupted as a result of the hypoxic environment, which causes a decrease in Adenosine triphosphate (ATP) concentrations [ 8 – 10 ]. The intracellular accumulation of Na+ causes cytotoxic edema in the brain leading to blood-brain barrier (BBB) disruption and the neurovascular unit composed of neurons, glia, endothelial cells, vascular smooth muscle, and immune cells [ 11 – 13 ]. Immune-mediated inflammatory response by activated neutrophils, reactive oxygen species produced by monocytes, and various types of matrix metalloproteinases contribute to this BBB disruption [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…The intracellular accumulation of Na+ causes cytotoxic edema in the brain leading to blood-brain barrier (BBB) disruption and the neurovascular unit composed of neurons, glia, endothelial cells, vascular smooth muscle, and immune cells [ 11 – 13 ]. Immune-mediated inflammatory response by activated neutrophils, reactive oxygen species produced by monocytes, and various types of matrix metalloproteinases contribute to this BBB disruption [ 13 – 15 ]. Other immune cells such as microglia and astrocytes along with endothelial cells also play major roles in the inflammatory response [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Immune-mediated inflammatory response by activated neutrophils, reactive oxygen species produced by monocytes, and various types of matrix metalloproteinases contribute to this BBB disruption [ 13 – 15 ]. Other immune cells such as microglia and astrocytes along with endothelial cells also play major roles in the inflammatory response [ 13 – 15 ]. Extravasation of blood and infiltration of inflammatory mediators such as cytokines and metalloproteinases into cerebral tissue are promoted by further damage to the endothelial layer of capillaries and increased permeability of the blood-brain barrier, resulting in HT [ 12 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…In a prospective study that consisted of 407 patients with ischemic strokes, researchers analyzed the frequency of spontaneous HT occurrence in relation to the infarcted area using CT and MRI techniques. Tan et al found that 50 patients (12.3%) suffered a spontaneous HT, with 66% of cases being HI and 34% being PH [ 13 ]. HT can present as asymptomatic or symptomatic, with severe neurological deficits due to profuse bleeding in the infarcted areas.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A Review of Risk Factors and Predictors for Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

Thomas

Plumber

Venkatapathappa

et al. 2021

International Journal of Vascular Medicine

View full text Add to dashboard Cite

Acute ischemic strokes (AIS) and hemorrhagic strokes lead to disabling neuropsychiatric and cognitive deficits. A serious and fatal complication of AIS is the occurrence of hemorrhagic transformation (HT). HT is cerebral bleeding that occurs after an ischemic event in the infarcted areas. This review summarises how specific risk factors such as demographic factors like age, gender, and race/ethnicity, comorbidities including essential hypertension, atrial fibrillation, diabetes mellitus, congestive heart failure, and ischemic heart disease along with predictors like higher NIHSS score, larger infarction size, cardioembolic strokes, systolic blood pressure/pulse pressure variability, higher plasma glucose levels, and higher body temperature during ischemic event, lower low-density lipoprotein and total cholesterol, early ischemic changes on imaging modalities, and some rare causes make an individual more susceptible to developing HT. We also discuss few other risk factors such as the role of blood-brain barrier, increased arterial stiffness, and globulin levels in patients postreperfusion using thrombolysis and mechanical thrombectomy. In addition, we discuss the implications of dual antiplatelet therapy and the length of treatment in reference to the incidence of developing HT. Current research into inflammatory mediators and biomarkers such as Cyclooxygenase-2, matrix metalloproteinases, and soluble ST2 and their potential role as treatment options for HT is also briefly discussed. Finally, this review calls for more research into use of dual antiplatelet and the timing of antiplatelet and anticoagulant use in reference to hemorrhagic transformation.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Review of Risk Factors and Predictors for Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

Thomas

Plumber

Venkatapathappa

et al. 2021

International Journal of Vascular Medicine

View full text Add to dashboard Cite

show abstract

“…The elevated BBB permeability persists in the subacute stage for 1–3 weeks and, to a lesser extent up to 6 weeks after stroke, spreading to its chronic period [ 42 ]. Prolonged BBB disfunction is believed to be associated with incomplete BBB recovery [ 58 ] due to activation of neuro- and angiogenesis [ 59 , 60 ]. Indeed, though the incidence of intracranial hemorrhage in stroke patients is highest during the first 30 days after stroke, it still remains higher than in the general population for at least one year thereafter [ 61 ].…”

Section: Blood–brain Barrier In Stroke and Its Response To Msc Transplantationmentioning

confidence: 99%

Cell Therapy of Stroke: Do the Intra-Arterially Transplanted Mesenchymal Stem Cells Cross the Blood–Brain Barrier?

Yarygin

Namestnikova

Sukhinich

et al. 2021

Cells

View full text Add to dashboard Cite

Animal model studies and first clinical trials have demonstrated the safety and efficacy of the mesenchymal stem cells’ (MSCs) transplantation in stroke. Intra-arterial (IA) administration looks especially promising, since it provides targeted cell delivery to the ischemic brain, is highly effective, and can be safe as long as the infusion is conducted appropriately. However, wider clinical application of the IA MSCs transplantation will only be possible after a better understanding of the mechanism of their therapeutic action is achieved. On the way to achieve this goal, the study of transplanted cells’ fate and their interactions with the blood–brain barrier (BBB) structures could be one of the key factors. In this review, we analyze the available data concerning one of the most important aspects of the transplanted MSCs’ action—the ability of cells to cross the blood–brain barrier (BBB) in vitro and in vivo after IA administration into animals with experimental stroke. The collected data show that some of the transplanted MSCs temporarily attach to the walls of the cerebral vessels and then return to the bloodstream or penetrate the BBB and either undergo homing in the perivascular space or penetrate deeper into the parenchyma. Transmigration across the BBB is not necessary for the induction of therapeutic effects, which can be incited through a paracrine mechanism even by cells located inside the blood vessels.

show abstract

Cerebral amyloid angiopathy and the immune system

Munsterman,

Falcione,

Long

et al. 2024

Alzheimer's & Dementia

Self Cite

View full text Add to dashboard Cite

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid protein in the walls of cerebral blood vessels. This deposition of amyloid causes damage to the cerebral vasculature, resulting in blood‐brain barrier disruption, cerebral hemorrhage, cognitive decline, and dementia. The role of the immune system in CAA is complex and not fully understood. While the immune system has a clear role in the rare inflammatory variants of CAA (CAA related inflammation and Abeta related angiitis), the more common variants of CAA also have immune system involvement. In a protective role, immune cells may facilitate the clearance of beta‐amyloid from the cerebral vasculature. The immune system can also contribute to CAA pathology, promoting vascular injury, blood‐brain barrier breakdown, inflammation, and progression of CAA. In this review, we summarize the role of the immune system in CAA, including the potential of immune based treatment strategies to slow vascular disease in CAA and associated cognitive impairment, white matter disease progression, and reduce the risk of cerebral hemorrhage.Highlights The immune system has a role in cerebral amyloid angiopathy (CAA) which is summarized in this review. There is an inflammatory response to beta‐amyloid that may contribute to brain injury and cognitive impairment. Immune cells may facilitate the clearance of beta‐amyloid from the cerebral vasculature. Improved understanding of the immune system in CAA may afford novel treatment to improve outcomes in patients with CAA.

show abstract

Hemorrhagic Transformation in Ischemic Stroke and the Role of Inflammation

Cited by 114 publications

References 137 publications

A Review of Risk Factors and Predictors for Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

A Review of Risk Factors and Predictors for Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

Cell Therapy of Stroke: Do the Intra-Arterially Transplanted Mesenchymal Stem Cells Cross the Blood–Brain Barrier?

Cerebral amyloid angiopathy and the immune system

Contact Info

Product

Resources

About