Inflammatory Responses in the Secondary Thalamic Injury After Cortical Ischemic Stroke

Abstract

Stroke is one of the major causes of chronic disability worldwide and increasing efforts have focused on studying brain repair and recovery after stroke. Following stroke, the primary injury site can disrupt functional connections in nearby and remotely connected brain regions, resulting in the development of secondary injuries that may impede long-term functional recovery. In particular, secondary degenerative injury occurs in the connected ipsilesional thalamus following a cortical stroke. Although secondary thalamic injury was first described decades ago, the underlying mechanisms still remain unclear. We performed a systematic literature review using the NCBI PubMed database for studies that focused on the secondary thalamic degeneration after cortical ischemic stroke. In this review, we discussed emerging studies that characterized the pathological changes in the secondary degenerative thalamus after stroke; these included excitotoxicity, apoptosis, amyloid beta protein accumulation, blood-brain-barrier breakdown, and inflammatory responses. In particular, we highlighted key findings of the dynamic inflammatory responses in the secondary thalamic injury and discussed the involvement of several cell types in this process. We also discussed studies that investigated the effects of blocking secondary thalamic injury on inflammatory responses and stroke outcome. Targeting secondary injuries after stroke may alleviate network-wide deficits, and ultimately promote stroke recovery.

Characterization of the Blood Brain Barrier Disruption in the Photothrombotic Stroke Model

“…Re-openings of the BBB have been observed days to weeks following the initial ischemic injury in clinical and pre-clinical research ( Huang et al, 1999 ; Kassner and Merali, 2015 ; Merali et al, 2017 ). Moreover, enhanced permeability has also been observed in regions not directly affected by the initial stroke due to retrograde or anterograde pathway degeneration and the associated inflammatory reaction ( Ling et al, 2009 ; Li et al, 2011 ; Cao et al, 2020 ). Therefore, we aimed to characterize the spatiotemporal profile of BBB permeability up to 3 weeks following stroke.…”

“…Onset and duration of secondary injury-induced BBB leakage can vary between 3 days after stroke and may be detectable up to 6 months in rodents and 12 months in patients ( Cao et al, 2020 ).…”

Neuronal Loss after Stroke Due to Microglial Phagocytosis of Stressed Neurons

“…( 1) 'Selective neuronal loss' may occur in peri-infact areas 1-7 days after transient middle cerebral artery occlusion (MCAO) in rodent striatum (and to a lesser extent in the cortex), but may increase over the following weeks [4,[7][8][9][10][11][12][13]. (2) 'Secondary neurodegeneration' of the thalamus may occur 0.5-12 months after cortical stroke [2,3,14]. There may also be hippocampal neurodegeneration secondary to cortical infarcts [15] and neurodegeneration in the midbrain secondary to infarcts in the striatum [16][17][18].…”

Distinctive Mediating Effects of Subcortical Structure Changes on the Relationships Between Amyloid or Vascular Changes and Cognitive Decline

“…However, the development of lacunes in the thalamus may affect decreased thalamic volume changes because the thalamic region is vulnerable to developing lacunes ( 40 , 41 ). Alternatively, lacunes might disrupt the thalamocortical connectivity, which in turn leads to decreased thalamic volume through secondary degeneration, such as Wallerian degeneration or dying back phenomenon ( 42 ).…”