Digoxin Ameliorates Glymphatic Transport and Cognitive Impairment in a Mouse Model of Chronic Cerebral Hypoperfusion / 神经科学通报·英文版

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.

Utilidad de la ecografía Doppler color en el seguimiento de la angioplastia carotídea / Doppler in Carotid Stent Follow-up

Los ataques cerebrovasculares (ACV), representan un problema mayor en salud y son una causa importante de discapacidad en todo el mundo. La estenosis u oclusión carotídea aterosclerótica causa alrededor del 20% de las isquemias cerebrovasculares.¹ Los ACV en los enfermos con estenosis carotídea se producen, en la mayoría de los casos, por la aparición de embolismos distales de trombo formado en la placa, oclusión trombótica aguda debido a rotura de la placa, o bien secundarios a las alteraciones hemodinámicas atribuibles a la estenosis, la cual produce disminución de la perfusión cerebral por el hipoflujo, en casos de estenosis críticas o suboclusivas. El tratamiento de la patología carotídea ha evolucionado de forma considerable a lo largo de los últimos años. Existen dos tratamientos invasivos para la estenosis carotídea significativa, que consisten en el abordaje quirúrgico con endarterectomía o tratamiento por vía percutánea con angioplastia y colocación de stent. En nuestra institución se realizaron, en el periodo comprendido entre marzo de 2013 y junio de 2017, aproximadamente 100 angioplastias carotídeas con colocación de stent. Todas fueron valoradas con ecografía Doppler color (EDC) al mes, a los seis meses y al año (en casos no complicados). En esta revisión bibliográfica es nuestra intención desarrollar las indicaciones, aplicaciones, hallazgos normales y patológicos en el examen de EDC en la evaluación de un paciente con stent carotídeo.

Acute stroke represents a major problem in health and is a major cause of disability worldwide. Atherosclerotic carotid stenosis or occlusion causes around 20% of cerebrovascular ischemias.¹ Stroke in patients with carotid stenosis occurs, in most cases, due to embolisms of thrombus formed in the plaque, acute thrombotic occlusion due to rupture of the plaque, or secondary to hemodynamic alterations, attributable to stenosis, which produces decreased cerebral perfusion by low flow, in cases of critical or sub occlusive stenosis. The treatment of carotid disease has evolved considerably over recent years. There are two invasive treatments for significant carotid stenosis, which consist of the surgical approach with endarterectomy or percutaneous treatment with angioplasty and stenting. In our institution, in the period between March 2013 and June 2017, ~100 carotid angioplasties with stent placement were performed. All were assessed with color Doppler ultrasound (DUS) at month, six months and one year (in non complicated cases). In this literature review it is our intention to develop the indications, applications, normal and pathological findings in the DUS examination in the evaluation of a patient with carotid stent.

Rescue Treatment with Intra-arterial Tirofiban Infusion and Emergent Carotid Stenting

Rapid arterial rethrombosis is associated with high-grade residual stenosis and usually occurs at the site of the initial occlusion, resulting in reocclusion of the recanalized artery. Platelets may play an active role in such rethrombosis after thrombolytic-induced clot lysis. Given that glycoprotein IIb/IIIa receptor blockers, like tirofiban, prevent thrombus formation by inhibiting the final common pathway of platelet aggregation, they may be helpful for treating rethrombosis after thrombolysis. A 64-year-old man presented with an acute ischemic stroke due to internal carotid artery (ICA) occlusion. The ICA was recanalized by intravenous thrombolysis but reoccluded shortly after recanalization. The reoccluded ICA was successfully recanalized using intra-arterial tirofiban. A carotid stent was subsequently inserted to relieve severe stenosis and to prevent recurrent stroke. Here, we report a case of rescue treatment of a successfully recanalized ICA by intra- arterial tirofiban. We suggest that rescue use of intra-arterial tirofiban may be effective and safe, especially in hemorrhage prone situations, due to the relatively lower dose of tirofiban compared with intravenous doses.

Enfermedad carotídea aterosclerosa y endarterectomía / Atherosclerotic carotid disease and endarterectomy

Se estima que aproximadamente la tercera parte de los infartos cerebrales están relacionados con embolismo de arteria a arteria, a su vez en relación directa con enfermedad aterosclerosa carotídea. La racionalidad de la endarterectomía carotídea se basa en la supuesta reducción del riesgo de EVC isquémico en pacientes con lesiones ateromatosas de la bifurcación carotídea (extracraneal), al realizar la reconstrucción de la arteria carótida interna y disecar por completo el ateroma, dejando la luz del vaso libre de restos del mismo. Como toda opción de tratamiento, el riesgo y el beneficio deben ser evaluados para conocer la bondad del recurso terapéutico. Resulta fundamental, por tanto, conocer el riesgo de EVC isquémico, que corre el paciente con lesión ateromatosa de la carótida cuando se le practica una endarterectomía, contrastándolo con el propio de seguir sólo un tratamiento médico (i.e, control de factores de riesgo y antiplaquetarios). Los estudios epidemiológicos primero, y los ensayos terapéuticos controlados y aleatorios después, han dejado en claro que los riesgos no son iguales para el paciente que nunca ha tenido un EVC en relación con la lesión carotídea aterosclerosa (sujetos asintomáticos), que para el sintomático. Por tanto, los beneficios y riesgos de la endarterectomía deben evaluarse de manera separada.