Low‐Dose Interleukin‐2 Reverses Traumatic Brain Injury‐Induced Cognitive Deficit and Pain in a Murine Model

作者：Katherine Czerpaniak, Leandro Flores do Nascimento, Tingting Guo, Jintao Zhang, Xuemei Liu, Mojdeh Sarzaeim, Zachary D. Fine, Yu‐Qing Cao · 发表于：Annals of Neurology · 年份：2024 · DOI：10.1002/ana.26998 · 被引用次数：5 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、Neuroinflammation and Neurodegeneration Mechanisms、Migraine and Headache Studies

OBJECTIVE: Despite the high prevalence, mild traumatic brain injury (mTBI)-induced chronic headache and cognitive deficits are poorly understood and lack effective treatments. Low-dose interleukin-2 (LD-IL-2) treatment soon after mTBI or overexpressing IL-2 in brain astrocytes prior to injury protects mice from developing post-traumatic headache (PTH)-related behaviors and cognitive decline. The present study addresses a clinically relevant knowledge gap: whether LD-IL-2 treatment long after the initial injury is still effective for chronic PTH and cognitive deficits. METHODS: mTBI was induced by a noninvasive closed-head weight drop method. LD-IL-2 was administered 4-6 weeks post-mTBI to assess its effects on chronic PTH-related facial mechanical hypersensitivity as well as mTBI-induced impairment in novel object recognition and object location tests. Endogenous regulatory T (Treg) cells were depleted to investigate the mechanism of action of LD-IL-2. RESULTS: Delayed LD-IL-2 treatment abolished chronic PTH-related behaviors. It also completely reversed mTBI-induced cognitive impairment in both male and female mice. Treg cell depletion not only prolonged PTH-related behaviors but also abolished the effects of LD-IL-2. Interestingly, LD-IL-2 treatment significantly increased the number of Treg cells in dura but not in brain tissues. INTERPRETATION: These results suggest that the beneficial effects of LD-IL-2 treatment are mediated through the expansion of meningeal Treg cells...