Depletion of Plasma Gelsolin in Patients with Tick-Borne Encephalitis and Lyme Neuroborreliosis

Abstract

Background/Aims: Cell damage during the course of inflammation results in cytoplasmic actin release, which if not eliminated by the extracellular actin scavenger system, composed of gelsolin and vitamin D binding protein, can cause dysfunction of hemostasis and toxicity towards surrounding cells. In this study, we test the hypothesis that an inflammatory reaction induced by central nervous system infections such as tick-borne encephalitis (TBE) or Lyme neuroborreliosis (LNB) will result in plasma gelsolin concentration changes in the blood and cerebrospinal fluid (CSF). Methods: Quantitative Western blot was used to determine gelsolin levels in 58 samples, which include: 29 patients without infection (diagnosed with conditions such as idiopathic cephalalgia, idiopathic Bell’s facial nerve palsy and ischialgia due to discopathy in which standard CSF diagnostic tests show no abnormalities), 12 patients diagnosed with TBE, and 17 patients diagnosed with LNB sub forma meningitis. Results and Conclusion: The gelsolin concentration in the blood of patients with TBE (163.2 ± 80.8 µg/ml) and LNB (113.6 ± 56.8 µg/ml) was significantly lower (p < 0.05 and p < 0.001, respectively) compared to the control group (226.3 ± 100.7 µg/ml). Furthermore, there was no statistically significant difference between the CSF gelsolin concentration in patients with TBE (3.9 ± 3.3 µg/ml), LNB (2.9 ± 1.2 µg/ml) and the control group (3.7 ± 3.3 µg/ml). An observed decrease in gelsolin concentration in the blood of TBE and LNB patients supports previous findings indicating the involvement of gelsolin in the pathophysiology of an inflammatory response. Therefore, evaluation of blood gelsolin concentration and administration of recombinant plasma gelsolin might provide a new tool to develop diagnostic and therapeutic strategies for TBE and LNB.

Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

“…A number of studies suggest the neuroprotective role of gelsolin and potential of hypogelsolinemia as a therapeutic target in the development for therapeutic interventions in some neurological illnesses, including ischemic stroke [ 133 ], Alzheimer’s disease [ 134 ], multiple sclerosis [ 67 ], tick-borne encephalitis and Lyme neuroborreliosis [ 66 ], and subarachnoid hemorrhage [ 135 ]. Furukawa et al and Endres et al, using gelsolin knock-out mice, demonstrated that gelsolin protects neurons against excitotoxic Ca 2+ overload via modulation of calcium influx through N-methyl-D-aspartate (NMDA) receptors and voltage-dependent Ca 2+ channels (VDCC) in hippocampal neurons.…”

Pathophysiological implications of actin-free Gc-globulin concentration changes in blood plasma and cerebrospinal fluid collected from patients with Alzheimer’s disease and other neurological disorders

“…The G-actin-gelsolin and G-actin-Gc-globulin complexes are primarily removed from the circulation by mononuclear phagocytes. 3,4 Low concentrations of Gc-globulin correspond to a poor prognostic outlook in acute liver failure, multiple organ dysfunction syndrome and sepsis. 5,6 Gc-globulin is also involved in the transport of vitamin D with its metabolites, fatty acids and endotoxins, functions in the activation of osteoclasts and macrophages, and serves as a chemotactic cue for leukocytes.…”

Increased levels of sphingosine-1-phosphate in cerebrospinal fluid of patients diagnosed with tick-borne encephalitis

“…These results suggest that the S1P pathway may partly govern the production of pro-inflammatory cytokines by astrocytes. Consequently, it is highly probable that the potential therapeutic effects of GSN (which has a significantly decreased concentration in the blood of TBE patients [ 45 ]) and FTY720P might be caused by modulation of S1P-mediated activation of astrocytes in the CNS. It was recently reported that FTY720 exposure might regulate specific neuroinflammatory responses by desensitizing astrocytes to external S1P [ 19 ].…”