Downstream Microvascular Thrombosis in Cortical Venules Is an Early Response to Proximal Cerebral Arterial Occlusion

نویسندگان

  • Jean‐Philippe Desilles
  • Varouna Syvannarath
  • Lucas Di Meglio
  • Célina Ducroux
  • William Boisseau
  • Liliane Louedec
  • Martine Jandrot‐Perrus
  • Jean‐Baptiste Michel
  • Mikael Mazighi
  • Benoît Ho‐Tin‐Noé
چکیده

BACKGROUND Previous experimental studies have shown that downstream microvascular thromboinflammation is involved in brain damage from acute ischemic stroke. Using intravital microscopy, we investigated and characterized the sequence of downstream microvascular thromboinflammation in an ischemia/reperfusion acute ischemic stroke model. METHODS AND RESULTS Rats underwent transient monofilament middle cerebral artery (MCA) occlusion. Cerebral microcirculation in the MCA territory was exposed through a craniotomy and analyzed using real-time intravital imaging coupled with laser Doppler interferometry. Leukocytes, platelets, fibrinogen, and blood-brain barrier permeability were analyzed by intravenous injection of fluorescent antibodies and bovine serum albumin. MCA occlusion induced a sudden and profound drop in downstream microvascular blood flow associated with leukocyte margination in the venous compartment. Leukocyte margination fostered fibrinogen deposition and thrombosis in postcapillary venules. Either in venules or arterioles, blood flow was not fully restored after MCA recanalization. Furthermore, venular thrombi persisted despite MCA recanalization, and leukocyte extravasation continued to develop in venules in association with blood-brain barrier disruption. Finally, microhemorrhages were occasionally observed, colocalizing with thrombosed venules characterized by marked leukocyte margination. CONCLUSIONS We showed that microvascular thrombosis in transient monofilament MCA occlusion and blood-brain barrier disruption are initiated immediately after occlusion and are propagated through the venous compartment in close association with marginating leukocytes. MCA occlusion-induced downstream microvascular thromboinflammation response was responsible for incomplete reperfusion after MCA recanalization and delayed microhemorrhages.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Albumin therapy of transient focal cerebral ischemia: in vivo analysis of dynamic microvascular responses.

BACKGROUND AND PURPOSE To study whether intravascular or hemodynamic factors contribute to the marked neuroprotective effect of albumin therapy in focal cerebral ischemia, 2 complementary methods were applied: laser-scanning confocal microscopy (LSCM) and laser-Doppler perfusion imaging (LDPI). METHODS In the LSCM study, Sprague-Dawley rats were anesthetized with halothane/nitrous oxide, and ...

متن کامل

Differential role of von Willebrand factor and P-selectin on microvascular thrombosis in endotoxemia.

OBJECTIVE Endotoxin (lipopolysaccharide [LPS]) enhances microvascular thrombosis in mouse cremaster venules. Because von Willebrand factor (vWF) and P-selectin are suggested to mediate LPS-induced platelet-microvessel interactions, we determined whether vWF and P-selectin contribute to microvascular thrombosis in endotoxemia. METHODS AND RESULTS A light/dye-induced thrombosis model was used i...

متن کامل

Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke.

BACKGROUND AND PURPOSE Leukocytes contribute to cerebral ischemia-reperfusion injury. However, few experimental models examine both in vivo behavior of leukocytes and microvascular rheology after stroke. The purpose of the present study was to characterize patterns of leukocyte accumulation in the cerebral microcirculation and to examine the relationship between leukocyte accumulation and micro...

متن کامل

Comparison effect of pentobarbital sodium with chloral hydrate anesthesia on post-ischemic damage in an experimental model of focal cerebral ischemia

Introduction: Anesthetic agents, blood pressure, arterial pH and blood gases have found to influence on the pathophysiology of experimental stroke. Despite, there are very few comparative studies about effects of anesthetic agents in animal model of cerebral ischemia. Therefore, in this study, we investigated the effects of chloral hydrate and pentobarbital anesthesia, as comparative study, on...

متن کامل

Microvascular Thrombosis and GP IIb/IIIa Inhibition in Stroke

Treatment options in acute stroke are limited by a dearth of safe and effective regimens for recanalization of an occluded cerebrovascular tributary, as well as by the fact that patients present only after the occlusive event is established. We hypothesized that even if the site of major arterial occlusion is recanalized after stroke, microvascular thrombosis continues to occur at distal sites,...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2018