Abstract
Background: Stroke patients with diabetes suffer from higher mortality rate and worsened neurological outcome. However, the responses of immune system to cerebral ischemia in the setting of diabetes remain poorly understood.Methods: In this study, we investigated the temporal profile of leukocyte mobilization and brain infiltration following distal middle cerebral artery occlusion (dMCAO) in db/db mouse model of type 2 diabetes (T2D) and its db/+ normoglycemic controls.Results: We found a significant increase of brain-infiltrating CD4+ T cell at day 3 after dMCAO, and a delayed and dramatic increase of brain-infiltrating neutrophils, CD4+ T cells, CD8+ T cells, and B cells at day 7 after dMCAO in db/db mice vs. db/+ controls. Leukocyte subsets in the circulation and spleen were also measured, however, there is no significant difference between non-diabetic and diabetic groups. Furthermore, we identified an increased expression of activation marker CD69 in brain-infiltrating neutrophils, CD4+ T and CD8+ T cells, and IFN-γ in brain-infiltrating CD4+ T cells in db/db mice at day 7 after dMCAO.Conclusions: These findings for the first time demonstrate that cerebral ischemia induces a delayed and sustained augmentation of brain infiltration and activation of neutrophils and lymphocytes in type 2 diabetic mice and these altered immune responses might contribute to the severer brain tissue damage and worse neurological outcomes of diabetes stroke, which warrants further investigation.
Highlights
Stroke is a leading cause of death and long-term disability accompanied by a major economic and healthcare burden
Given that inflammation is a key participant in brain injury and recovery after ischemia, and that the immune system and its responses to injury is profoundly altered in diabetes, how the immune system respond to cerebral ischemia in the setting of diabetes remains a fundamental yet unanswered question
To explore the potential role of infiltrated leukocytes in the ischemic brain inflammation process of type 2 diabetes (T2D) stroke, for the first step, in this study we investigated the temporal profile of leukocyte mobilization and infiltration in adult db/db mice following distal middle cerebral artery occlusion (dMCAO)
Summary
Stroke is a leading cause of death and long-term disability accompanied by a major economic and healthcare burden. Among the prominent risk factors of stroke, diabetes mellitus (DM) has been linked to higher mortality rate and worsened neurological outcome in stroke patients [1,2,3]. 30% of stroke patients are diabetic [4, 5], the underlying mechanisms. Exacerbated Brain Inflammation in Diabetic Stroke responsible for the increased post-ischemic brain injury in subset of stroke patients remain poorly understood. 90% of DM patients suffer from type 2 diabetes (T2D). Stroke patients with diabetes suffer from higher mortality rate and worsened neurological outcome. The responses of immune system to cerebral ischemia in the setting of diabetes remain poorly understood
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