Progressive Reparative Gliosis in Aged Hosts and Interferences with Neural Grafts in an Animal Model of Huntington's Disease

Abstract

1. Neural transplantation in Huntington's diseased patients is currently the only approach in the treatment of this neurodegenerative disorder. The clinical trial, unfortunately, includes only a small number of patients until now, since many important questions have not been answered yet. One of them is only mild to moderate improvement of the state in most of grafted patients. 2. We examined the morphological correlates in the response to intrastriatal grafting of fragments of foetal rat ventral mesencephalic tissue 1 month after transplantation in male Wistar rats within varying durations (from 2 to 38 weeks) of experimentally induced neurodegenerative process of the striatum (used as a model of Huntington's disease). Our goal was to determine the impact of advanced striatal damage and gliosis on the graft viability and host-graft integration. 3. The findings can be summarized as follows: The progressive reactive gliosis, which is not able to compensate continual reduction of the grey matter leading to an extensive atrophy of the striatum in a long-term lesions, results in formation of the compact glial network. This tissue cannot be considered the suitable terrain for successful graft development and formation of host-graft interconnections. 4. The progression of irreversible morphological changes in long-lasting neurodegenerative process within the striatum can be supposed one of the important factors, which may decrease our prospect of distinct improvement after neural grafting in patients in advanced stage of Huntington's disease, who still remain the leading group in clinical trials.

Transgenic Rat Model of Huntington’s Disease: A Histopathological Study and Correlations with Neurodegenerative Process in the Brain of HD Patients

“…The intensity and extent of the reactive gliosis are determined primarily by signals from damaged cells (e.g., [56, 57]). Up to now, the origin and the way by which the increased number of astrocytes appears in damaged CNS are not fully elucidated and still remain a matter of intensive debate.…”

Neuronal damage is much delayed and microgliosis is more severe in the aged hippocampus induced by transient cerebral ischemia compared to the adult hippocampus

“…Astrocytes play important roles in several processes, such as the regulation of ion homeostasis, neurotransmission and neuronal functions, in the central nervous system [1][2][3]. It has been known that astrocytes can promote synapse formation and maintain and modulate synaptic function [4].…”

Blueberry supplementation attenuates microglial activation in hippocampal intraocular grafts to aged hosts

“…Glial activation can be detrimental to neural cell survival in a number of transplantation paradigms, including animal models of spinal cord injury (Beattie 2004), Parkinson's Disease (Duan et al, 2000; Sortwell et al, 2001), and Huntington's disease (Mazurova et al, 2006; Johann et al, 2007). The activation of inflammatory processes in transplanted neural tissue is thought to stem, in part, from the introduction of foreign cells into a damaged, diseased, or dysfunctional environment, and is also thought to be aggravated by the surgical procedure itself (Bastian et al, 2008).…”