High fat diet accelerates and exacerbates microgliosis and neuronal damage/death in the somatosensory cortex after transient forebrain ischemia in gerbils

Won Joo Seo,Myoung Cheol Shin,Joon Ha Park,Tae-Kyeong Lee,Jun Hwi Cho,Yoonsoo Park,Yeon Ho Yoo,Ji Hyeon Ahn,Bora Kim,Jae-Chul Lee,Moo-Ho Won

doi:10.1186/s42826-020-00061-1

Abstract

Obesity has been known as an independent risk factor for stroke. Effects of high-fat diet (HFD)-induced obesity on neuronal damage in the somatosensory cortex of animal models of cerebral ischemia have not been studied yet. In this study, HFD-induced obesity was used to study the impact of obesity on neuronal damage/loss and microgliosis in the somatosensory cortex of a gerbil model of 5-min transient forebrain ischemia. We used gerbils fed normal diet (ND) and HFD and chronologically examined microgliosis (microglial cell activation) by ionized calcium-binding adapter molecule 1 (Iba-1) immunohistochemistry. In addition, we examined neuronal damage or death by using neuronal nuclear protein (NeuN, a neuronal marker) immunohistochemistry and Fluoro-Jade B (F-J B, a marker for neuronal degeneration) histofluorescence staining. We found that ischemia-induced microgliosis in ND-fed gerbils was increased from 2 days post-ischemia; however, ischemia-mediated microgliosis in HFD-fed gerbils increased from 1 day post-ischemia and more accelerated with time than that in the ND-fed gerbils. Ischemia-induced neuronal death/loss in the somatosensory cortex in the ND-fed gerbils was apparently found at 5 days post-ischemia. However, in the HFD-fed gerbils, neuronal death/loss was shown from 2 days post-ischemia and progressively exacerbated at 5 days post-ischemia. Our findings indicate that HFD can evoke earlier microgliosis and more detrimental neuronal death/loss in the somatosensory cortex after transient ischemia than ND evokes.

Highlights

Obesity caused by high-fat diet (HFD) is one of the most serious public health problems worldwide
Our findings indicate that HFD can evoke earlier microgliosis and more detrimental neuronal death/loss in the somatosensory cortex after transient ischemia than normal diet (ND) evokes
We recently reported that the level of blood glucose, triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels were significantly increased in this gerbil model of HFD [1]

Summary

Introduction

Obesity caused by high-fat diet (HFD) is one of the most serious public health problems worldwide. HFD fed rats and mice for 8–12 weeks profoundly increases cerebral infarction following transient focal cerebral ischemia [1, 8, 9, 14]. Transient ischemic insults in the brain causes neuronal damage and death in vulnerable regions and leads to severe neurologic impairments [15, 16]. Ischemia/ reperfusion injury following transient global cerebral ischemia is a major cause of neurologic abnormalities, including seizures, delirium, neurocognitive impairment, etc. It has been demonstrated that many regions of the brain are selectively vulnerable to transient global cerebral ischemia [18]. It has been reported that, in the somatosensory cortex, pyramidal cells in layer III and pyramidal cells in the upper part of layer VI are much more sensitive to ischemia than the other cortical neurons [19]. Somatosensory inputs control complex senses and complex movements, the somatosensory cortex is crucial in neural rehabilitation in patients with brain lesions [17, 19, 24, 25]

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