Characterization of Inflammation in Delayed Cortical Transplantation

Abstract

We previously reported that embryonic motor cortical neurons transplanted 1-week after lesion in the adult mouse motor cortex significantly enhances graft vascularization, survival, and proliferation of grafted cells, the density of projections developed by grafted neurons and improves functional repair and recovery. The purpose of the present study is to understand the extent to which post-traumatic inflammation following cortical lesion could influence the survival of grafted neurons and the development of their projections to target brain regions and conversely how transplanted cells can modulate host inflammation. For this, embryonic motor cortical tissue was grafted either immediately or with a 1-week delay into the lesioned motor cortex of adult mice. Immunohistochemistry (IHC) analysis was performed to determine the density and cell morphology of resident and peripheral infiltrating immune cells. Then, in situ hybridization (ISH) was performed to analyze the distribution and temporal mRNA expression pattern of pro-inflammatory or anti-inflammatory cytokines following cortical lesion. In parallel, we analyzed the protein expression of both M1- and M2-associated markers to study the M1/M2 balance switch. We have shown that 1-week after the lesion, the number of astrocytes, microglia, oligodendrocytes, and CD45+ cells were significantly increased along with characteristics of M2 microglia phenotype. Interestingly, the majority of microglia co-expressed transforming growth factor-β1 (TGF-β1), an anti-inflammatory cytokine, supporting the hypothesis that microglial activation is also neuroprotective. Our results suggest that the modulation of post-traumatic inflammation 1-week after cortical lesion might be implicated in the improvement of graft vascularization, survival, and density of projections developed by grafted neurons.

Nalbuphine Alleviates Inflammation by Down-regulating NF-κB in an Acute Inflammatory Visceral Pain Rat Model

“…The white matter is composed of oligodendrocyte precursor cells (OPCs), oligodendrocytes, astrocytes, and microglia [55]. Macrophage/microglia are extensively involved in the process of in ammatory response in the central nervous system [56,57]. Our results also suggested that spinal macrophage/microglia are also involved in the development of in ammatory visceral pain.…”

Better Outcomes with Intranigral versus Intrastriatal Cell Transplantation: Relevance for Parkinson’s Disease

“…Different activation statuses of microglial cells can promote either neurotoxicity or neuroprotection [ 97 , 99 , 100 ]. In our study, we found that most of the activated microglial cells expressed a pro-inflammatory marker in host tissue surrounding and within the intrastriatal grafts to a greater extent than the intranigral grafts.…”

Axonal Extensions along Corticospinal Tracts from Transplanted Human Cerebral Organoids

“…However, the mechanism through which the host brain 1 week after the resection supports cell survival and axonal extension is unknown. Previous studies suggest that the secretion of pro-angiogenic factors by cells surrounding the lesion ( Skold et al., 2005 ) or the modulation of inflammatory responses ( Ballout et al., 2019 ; Liauw et al., 2008 ) are candidates. It is reported that transplantation with 1-week delay provided a transient increase in graft vascularization 4 days after the transplantation ( Peron et al., 2017 ).…”

“…We found that 10w-organoids, which are in the CPN-generating stage, have a lower risk of graft overgrowth. In previous studies describing the transplantation of embryonic cerebral cortex, E14-E15 mice, which corresponds to the CPN-generating stage, were used as the grafts (Ballout et al, 2016(Ballout et al, , 2019Gaillard et al, 2004Gaillard et al, , 2007Peron et al, 2017), which would explain why graft overgrowth did not become a problem in those studies.…”