Yuan Shan1, Jun Hu1, Hua Lv1, Xiaoli Cui1, Wei Di2. 1. Department of Neurology, Shaanxi Provincial People's Hospital, No. 256 West Friendship Rd, Xi'an, China, 710068. 2. Department of Neurology, Shaanxi Provincial People's Hospital, No. 256 West Friendship Rd, Xi'an, China, 710068. Electronic address: slsdxw@163.com.
Abstract
BACKGROUND: Ischemic stroke is clearly affected by microRNAs (miRNAs) due to dysfunction of their regulatory networks. Our clinical data confirmed decreased miR-221 levels in plasma collected from patients with acute ischemia compared with plasma from healthy controls. Therefore, we further aimed to demonstrate the regulatory mechanisms by which miR-221 exerts its neuroprotective effects in acute ischemic brain injury. METHODS: Middle cerebral artery occlusion (MCAO) was used to establish focal cerebral ischemia in adult male C57BL/6 mice. A miR-221 mimic or a negative mimic control was injected by intracerebroventricular administration 24 h prior to MCAO. After 48 h, cerebral infarction volume and neurological scores were calculated, and to determine the extent of neuroprotection by miR-221, neurobehavioral tests were performed. Quantitative real-time PCR, ELISA, and flow cytometry were also performed to identify the expression of inflammation-related cytokines and chemokines as well as infiltration/activation of various immune cells in the brain. RESULTS: The results showed that MCAO mice treated with a miR-221 mimic exhibited significantly decreased cerebral infarction volume and increased amelioration of behavioral deficits. Moreover, the expression of proinflammatory cytokines (TNF-α, MCP-1, VCAM-1, and IL-6) and chemokines (CCL2 and CCL3) was significantly decreased in the miR-221 mimic-treated group. In addition, the flow cytometry data showed that macrophage infiltration and microglial activation were blocked by miR-221 treatment. CONCLUSION: our results indicate that miR-221 could decrease brain damage in the setting of acute ischemic stroke by inhibiting the proinflammatory response, which furthered our understanding of the molecular basis of miR-221 and provided a new potential therapeutic target for the treatment of ischemic stroke .
BACKGROUND:Ischemic stroke is clearly affected by microRNAs (miRNAs) due to dysfunction of their regulatory networks. Our clinical data confirmed decreased miR-221 levels in plasma collected from patients with acute ischemia compared with plasma from healthy controls. Therefore, we further aimed to demonstrate the regulatory mechanisms by which miR-221 exerts its neuroprotective effects in acute ischemic brain injury. METHODS: Middle cerebral artery occlusion (MCAO) was used to establish focal cerebral ischemia in adult male C57BL/6 mice. A miR-221 mimic or a negative mimic control was injected by intracerebroventricular administration 24 h prior to MCAO. After 48 h, cerebral infarction volume and neurological scores were calculated, and to determine the extent of neuroprotection by miR-221, neurobehavioral tests were performed. Quantitative real-time PCR, ELISA, and flow cytometry were also performed to identify the expression of inflammation-related cytokines and chemokines as well as infiltration/activation of various immune cells in the brain. RESULTS: The results showed that MCAOmice treated with a miR-221 mimic exhibited significantly decreased cerebral infarction volume and increased amelioration of behavioral deficits. Moreover, the expression of proinflammatory cytokines (TNF-α, MCP-1, VCAM-1, and IL-6) and chemokines (CCL2 and CCL3) was significantly decreased in the miR-221 mimic-treated group. In addition, the flow cytometry data showed that macrophage infiltration and microglial activation were blocked by miR-221 treatment. CONCLUSION: our results indicate that miR-221 could decrease brain damage in the setting of acute ischemic stroke by inhibiting the proinflammatory response, which furthered our understanding of the molecular basis of miR-221 and provided a new potential therapeutic target for the treatment of ischemic stroke .
Authors: Barend W Florijn; Roel Bijkerk; Nyika D Kruyt; Anton Jan van Zonneveld; Marieke J H Wermer Journal: Int J Mol Sci Date: 2021-11-02 Impact factor: 5.923
Authors: Sandy R Shultz; Caroline J Taylor; Riemke Aggio-Bruce; William T O'Brien; Mujun Sun; Adrian V Cioanca; George Neocleous; Georgia F Symons; Rhys D Brady; Anandwardhan A Hardikar; Mugdha V Joglekar; Daniel M Costello; Terence J O'Brien; Riccardo Natoli; Stuart J McDonald Journal: Biomark Insights Date: 2022-02-28