Neuroinflammatory penumbra in Parkinson’s disease

V.V Ponomarev,N.E Aleinikava,V.A Bahamaz,T.Y Kuznetsova,A.V Boika,Z.A Hladkova,M.M Sialitski

doi:10.22141/2224-0713.17.5.2021.240918

Abstract

To date, the etiology and pathogenesis of Parkinson’s disease (PD) are not fully understood. In this publication, we present a critical review of the available international data on the involvement of inflammation processes in the etiopathogenesis of the disease in the context of our research results. The data obtained by us during modeling of parkinsonian syndrome of neuroinflammatory origin (lipopolysaccharide endotoxin was used) in laboratory rats (basic group, n = 21; control group, n = 7) indicate that intranasal administration of lipopolysaccharide in all three studied doses (1, 10 and 100 μg/kg/ml) seven days after the end of the experiment (21 injections) causes the same moderate morphological degenerative and inflammatory changes in the histostructure of the substantia nigra, extending to the striatum area (p > 0.05). This fact can be best explained by the all-or-none law. The staged, sequential transition of primary reversible (neuroinflammatory) pathomorphological changes to secondary irreversible (neurodegenerative) ones in PD, as well as secondary activation of microglia during neuronal degeneration, allows proposing the term “neuroinflammatory penumbra”, which will best help understand the pathogenesis of the disease and the development of therapies that change the course of Parkinson’s disease. Our data on the use of mesenchymal multipotent stromal cells in rats with neurotoxic (rotenone) parkinsonian syndrome (n = 10) and in PD individuals (n = 10) demonstrate a decrease in motor impairment, overall improvement of patients and an effect on laboratory parameters compared with control groups. We associate the early positive effect, observed already in the first week after the administration of mesenchymal multipotent stromal cells, with their paracrine action, including on the neuroinflammatory penumbra.

Highlights

Parkinson’s disease (PD) is one of the most common ones in neurological practice, which are traditionally attributed to the group of conformational pathology of the brain [1]
Etiologies of parkinsonism: pathomechanisms and clinical implications” [7] at the end of which the accumulated data in recent years indicated the role of infectious etiology in the development of parkinsonism and Parkinson’s disease, but the authors caution against the conclusion that all cases of PD are associated with increased inflammatory reactions and underlying chronic infection
Our data [12, 13] obtained by comparing the results of repeated laboratory studies of dopamine and homovanillic acid levels in the blood serum and cerebrospinal fluid of experimental animals on days 7 and 21 from the beginning of modeling parkinsonial syndrome of neuroinflammatory (LPS was used, n = 6) and neurotoxic origin showed progressive neurotransmitter deficiency in animals of both groups, which indicates the validity of the neuroinflammatory and neurotoxic models of parkinsonism used to study the pathogenesis of PD [14, 15]

Summary

Introduction

Parkinson’s disease (PD) is one of the most common ones in neurological practice, which are traditionally attributed to the group of conformational pathology of the brain (substantia nigra pars compacta) [1].

Results

Conclusion