α4 integrin is a regulator of leukocyte recruitment after experimental intracerebral hemorrhage

MD Hammond, WG Ambler, Y Ai, LH Sansing - Stroke, 2014 - Am Heart Assoc
MD Hammond, WG Ambler, Y Ai, LH Sansing
Stroke, 2014Am Heart Assoc
Background and Purpose—Intracerebral hemorrhage (ICH) is swiftly followed by an
inflammatory response. A key component of this response is the recruitment of leukocytes
into the brain, which promotes neurological injury in rodent models. However, the
mechanisms by which leukocytes transmigrate across the endothelium into the injured brain
are unclear. The present study examines leukocyte adhesion molecules (α4 integrin, L-
selectin, and αLβ2 integrin) on 4 leukocyte subtypes to determine which are important for …
Background and Purpose
Intracerebral hemorrhage (ICH) is swiftly followed by an inflammatory response. A key component of this response is the recruitment of leukocytes into the brain, which promotes neurological injury in rodent models. However, the mechanisms by which leukocytes transmigrate across the endothelium into the injured brain are unclear. The present study examines leukocyte adhesion molecules (α4 integrin, L-selectin, and αLβ2 integrin) on 4 leukocyte subtypes to determine which are important for leukocyte recruitment after ICH.
Methods
We used the blood injection mouse model of ICH, whereby 25 μL of blood was injected into the striatum. Flow cytometry was used to quantify leukocyte populations and adhesion molecule expression in brain and blood. An α4 integrin–blocking antibody was administered to evaluate the contribution of α4 integrin in leukocyte migration and neurological injury.
Results
α4 integrin was elevated on all leukocyte populations in brain after ICH, whereas L-selectin was unchanged and αLβ2 was increased only on T cells. Antagonism of α4 resulted in decreased leukocyte transmigration and lessened neurobehavioral disability.
Conclusions
α4 integrin is an important cell adhesion molecule involved in neuroinflammation after ICH.
Am Heart Assoc