Glymphatic system in the thalamus, secondary degeneration area was severely impaired at 2nd week after transient occlusion of the middle cerebral artery in rats

Abstract

Background and objectivesThe glymphatic system is a recently discovered cerebrospinal fluid transport system and little is known about its dynamic changes after stroke. This study aimed to dynamically observe the structural and functional changes of the impaired glymphatic system in the thalamus after ischemic stroke by pathology and MRI.Materials and methodsIschemic stroke was induced by the middle cerebral artery occlusion (MCAO) model. A total of 20 Sprague-Dawley rats were randomly assigned into four groups: sham, MCAO 1 week, MCAO 2 week, and MCAO 2 month. All rats successively underwent neurological examination, dynamic contrast-enhanced MRI (DCE-MRI), and immunofluorescence staining. Immunofluorescence staining of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), ionized calcium-binding adaptor molecule 1 (Iba1), and beta-amyloid precursor protein (APP) were done in thalamus ventroposterior nucleus.ResultsThe astrocyte and microglial activation and the APP deposition in the MCAO 2 week group were the highest (P < 0.05 for all). The AQP4 polarization rates of the MCAO 2 week and 2 month groups were the lowest (P < 0.05 for all). Although there was no correlation between histological changes and MRI metrics in all four groups (P > 0.05 for all), the tendency of the APP deposition was nearly consistent with the one of the contrast agent retention in DCE-MRI.ConclusionThe glymphatic system in the thalamus was severely impaired at 2nd week after MCAO, and may be revealed by DCE-MRI. This study may provide a relevant theoretical basis for making a thorough inquiry of the mechanism of brain injury after stroke and clinical treatment of ischemic stroke and help readers appreciate the importance of DCE-MRI.

The glymphatic system: a new perspective on brain diseases

“…However, in recent years, Panoptic imaging of transparent mice has also been used to analyze the distribution of tracers in the brain ( Bèchet et al, 2020 ). Imaging in vivo is mainly utilized to observe the flow of CSF in the brain by injecting a CSF tracer into the cisterna magna and using two-photon fluorescence imaging (TPI) ( Iliff et al, 2013b ; Tithof et al, 2019 ), near-infrared fluorescence (NIRF) ( Myllylä et al, 2018 ), transcranial optical imaging ( Plog et al, 2018 ), magnetic resonance imaging(MRI) ( Bai et al, 2022 ; Li C. et al, 2022 ) and so on. TPI has high spatial resolution and can observe 240μm below the cortical surface, which is conducive to observing the diffusion of the CSF tracer along the outside of cortical surface arteries and penetrating arterioles ( Iliff et al, 2012 ).…”

The glymphatic system for neurosurgeons: a scoping review

“…Ischemic and hemorrhagic strokes have also been investigated in terms of their effect on the glymphatic system [25,[34][35][36][37][38][39][40][41][42][43][44][45][46]. See Supplemental Table 2 for an overview of the 14 included articles spanning 10 animal and 4 human studies.…”

“…In mice, middle carotid artery occlusion (MCAO) resulted in reduced parenchymal penetration of both fluorescent tracer and MRI contrast agent, along with an impairment of perivascular polarity of AQP4 and impairment of glymphatic system in thalamus [42,45]. The post-stroke edema was also investigated in mice, where intravenous and intracisternal administration of 22 Na and 3 H-mannitol revealed a predominant influx of CSF into the edematous tissue from the lateral ventricles, cisterna magna, and the PVS [35].…”

A bibliometric analysis of the glymphatic system in cognition from 2009 to 2023

“…Mouse models of cognitive dysfunction included APP/PS1 [28]. middle cerebral artery occlusion (MCAO) [29]. bilateral common carotid artery stenosis (BCAS) [30] and so on.…”