High salt and stroke

Background

High-salt intake is positively correlated with blood pressure, blood lipid concentration, circulating alarmins, and other factors leading to detrimental stroke prognosis.

 The habit of high-salt diet (HSD) has long been considered as a risk factor for acute ischemic stroke (AIS) [1–3].

 Therefore, salt restriction is widely accepted as a 

vital step in efficient lifestyle intervention to prevent new vascular events, especially AIS [4–6]. 

Nevertheless, in daily clinical practice, we found that it was not always practical for patients to change the long-established high-salt diet. Therefore, there is an unmet need to develop therapeutic strategies to tackle the already existing high salinity and the associated pathophysiology.

Macrophage, as an innate immune cell, has a high degree of parallelism and flexibility [7, 8].

 Macrophages could release multiple proinflammatory mediators or efficiently sweep cell debris and 

promote neural recovery. The phenotypic shift of macrophages depends largely on the cues of the microenvironment [9, 10].

 Recent research has elucidated that surplus dietary salt shifts macrophages/microglia towards the

 classical activated proinflammatory phenotype, which is often referred to as M1 [11]

, indicating that excessive salt intake breaks the M1/M2 macrophages balance and further aggravates the inflammatory response. In vivo, the proinflammatory property of macrophages in HSD-fed mice contributed to blood-brain barrier (BBB) disruption after stroke and exacerbated stroke outcomes [12].

 Efferocytosis represents a vital anti-inflammatory

 process of macrophages. Timely clearance of cell debris and cell corpses is essential for subsequent tissue reconstruction of lesions [9, 13, 14]. Nevertheless, the impact of HSD on phagocytic activity and the subsequent anti-inflammatory functions of macrophages remain elusive.

The current study investigated the impact of excessive salt intake on the efferocytic capacity of macrophages after ischemic stroke. Our data indicated that HSD downregulated the expression of the phagocytic molecule triggering receptor expressed on myeloid cells 2 (TREM2) in macrophages, thus impeding their debris clearing activities. Enhancement of TREM2 signaling in macrophages rescued the inflammation resolving functions and displayed delightful therapeutic effects. TREM2 could be a promising therapeutic target of AIS, especially in patients with un-converted HSD habits.

J Neuroinflammation. 2021 Apr 12;18:90. doi: 10.1186/s12974-021-02144-9

High-salt diet downregulates TREM2 expression and blunts efferocytosis of macrophages after acute ischemic stroke

Mengyan Hu 1,#, Yinyao Lin 1,#, Xuejiao Men 1,#, Shisi Wang 1, Xiaobo Sun 1, Qiang Zhu 1, Danli Lu 1, Sanxin Liu 1, Bingjun Zhang 1, Wei Cai 1,2,✉, Zhengqi Lu 1,✉