Intra-arterial transplantation of neural stem cells improve functional recovery after transient ischemic stroke in adult rats

Abstract

OBJECTIVES: The neural stem cell transplantation has been proposed as alternative therapy to promote functional recovery after various neurological disorders. The aim of this study was to evaluate the effect of intra-arterial transplantation of adult neural stem cells on improving local brain ischemia injuries. MATERIALS AND METHODS: In this study, 32 male Wistar rats were used. Ischemia was induced using a middle cerebral artery obstruction with monofi lament nylon suture. Neural stem cells were isolated from subventricular zone of the rat brain. 24 hours after local ischemia, the cells were labeled with DiI and transplanted intra-articularly. Evaluation of neurological movement defi cits was performed using a neurological defi cit score. The transplanted neural stem cells differentiation into neurons and astrocytes was assessed by immunohistochemistry. RESULTS: The results indicated that lesion volumes in the ischemic control, PBS and the treatment groups were 31.5, 29.8 and 14.7 % respectively. Our results also showed that the number of eosinophilic neurons and also neurological impairment in the treatment group was signifi cantly reduced compared to the control and PBS groups. CONCLUSION: The results suggested that intra-arterial transplantation of neural stem cells 24 hours after ischemia, led to a decrease in the volume of brain ischemic lesion and improved neurological outcomes (Fig. 7, Ref. 23).

Intra-Arterial Stem Cell Transplantation in Experimental Stroke in Rats: Real-Time MR Visualization of Transplanted Cells Starting With Their First Pass Through the Brain With Regard to the Therapeutic Action

“…In contrast, Andres et al (2011) revealed simultaneous decrease of infarct size and neurological deficit at day 3 post-stroke in mice receiving mouse postnatal C-C chemokine receptor 2 (CCR2 + / +) NSC. Similar results were reported by Kondori et al (2020) after adult rat NSC transplantation. Though exact causes of the described differences are not clear, they are probably due to the variations of the properties of transplanted cells themselves that is related to their origin and culture conditions.…”

“…A number of preclinical studies have demonstrated that neural stem/precursor cells (NSC/NPC) derived from the other sources (from adult or fetal brain tissues, embryonic stem cells, induced pluripotent stem cells) have also promoted functional recovery after intra-arterial transplantation into animal models of stroke ( Andres et al, 2011 ; Doeppner et al, 2015 ; Rosenblum et al, 2015 ; Kondori et al, 2020 ). However, the extent of the positive effects have been somewhat different.…”

Recent Advances in Cell-Based Therapies for Ischemic Stroke

“…As shown in Table 2, many studies have assessed NSC transplantation to treat ischemic brain injury in animal models. The initial hypotheses were based on the assumption that NSCs would replace lost neurons and restore connections in neuronal circuitry [94][95][96][97][98][99][100][101][102][103][104][105][106]. Indeed, analysis of graft-derived neuronal cells using immuno-electron microscopy and electrophysiological recording demonstrated increased connectivity, showing that NSCs could develop into functioning neurons to contribute to improved recovery from stroke and brain injury in rats [107,108].…”

“…Although transplanted NSCs are expected to differentiate into various neural cells rather than other stem cells, it remains unclear to what extent this contributes to functional recovery. The current understanding is that transplanted NSCs likely prevent neuronal apoptosis, exert immunomodulatory effects inside and outside the brain, increase endogenous neuronal regeneration and angiogenesis, and inhibit glial scar formation mainly via paracrine and autocrine secretion of various neurotrophic factors rather than differentiation [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 109 , 110 ] ( Table 2 ).…”

Prospects of Therapeutic Target and Directions for Ischemic Stroke

“…To adequately investigate stem cell therapies for neurological diseases in preclinical studies, it is very important to develop imaging technologies that are able to evaluate disease progression by “chasing” (i.e., tracking or monitoring) transplanted stem cells in recipients. The pathology of stroke and regeneration by transplanted stem cells develop through either endogenous or exogenous mechanisms, which can be assessed using various imaging technologies, including traditional tissue staining, immunohistochemistry, autoradiography, electrophysiological analysis, and molecular biological methods [ 115 , 116 ].…”