IL-10 Overexpression Improves Cerebral Microcirculation and Attenuates Cerebral Vasospasm After Experimental SAH
BACKGROUND: Subarachnoid hemorrhage (SAH) induces inflammatory responses and subsequent immune cell activation, which may contribute in cerebral vasospasm, microcirculatory impairment and poor neurological outcomes. Although cerebral vasospasm has traditionally been considered a major cause of delayed cerebral ischemia after SAH, therapies targeting angiographic vasospasm have not consistently…
Subarachnoid hemorrhage (SAH) can lead to inflammation and immune cell activation, potentially resulting in cerebral vasospasm, microcirculatory impairment, and poor neurological outcomes. While targeting angiographic vasospasm has not consistently improved functional results, early inflammatory responses might contribute to these complications. This study aimed to determine if interleukin-10 (IL-10), an anti-inflammatory cytokine, could enhance outcomes in an experimental SAH model.
Mice were injected either with an adeno-associated virus encoding IL-10 (AAV/IL-10) or an AAV expressing green fluorescent protein (AAV/GFP) as control. Researchers assessed cerebral vasospasm, microcirculatory impairment, and cerebral perfusion using India ink angiography, measuring the sphenoidal segment of the middle cerebral artery (MCA), total length of cortical arteries, and cortical staining intensity, respectively.
Perivascular inflammatory cell infiltration and cytokine levels were examined via immunohistochemistry and ELISA. The therapeutic efficacy of the AAV/IL-10 vector was also evaluated when administered immediately after SAH.
IL-10 overexpression led to improved neurological outcomes after SAH and was linked to reduced cerebral vasospasm and microcirculatory impairment, as well as better preservation of cerebral perfusion. Additionally, it significantly decreased neutrophil and macrophage infiltration around the internal carotid artery and mitigated SAH-induced increases in IL-6 and matrix metalloproteinase-3 levels.
Mice treated with the AAV/IL-10 vector shortly after SAH exhibited notable improvements in neurological scores and cerebral perfusion.
These findings suggest that AAV-mediated IL-10 overexpression can enhance neurological outcomes after SAH, likely by dampening inflammatory responses, cerebral vasospasm, and microcirculatory impairment. The researchers conclude that IL-10-based anti-inflammatory therapy could be a promising strategy for treating SAH.
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