Cerebrospinal fluid activity of tissue plasminogen activator in patients with neurological diseases.

Abstract

Aim-To study cerebrospinal fluid (CSF) activity of tissue plasminogen activator (tPA) in patients with neurological diseases.Methods-CSF tPA and urokinase (uPA) activities were studied using an immunocapture assay and zymography in 44 patients with neurological disease and 20 reference subjects. The patient group comprised three patients with meningitis, 21 with encephalitis, nine with acute lymphoblastic (n = 7) and myeloid (n = 2) leukaemia, seven with multiple sclerosis, three with facial paresis, and one with polyradiculitis. Results-Raised tPA activities were observed in patients with multiple sclerosis, leukaemia and encephalitis. In contrast, there were no differences in the mean activities of tPA in patients with meningitis or other diseases compared with the reference subjects. The highest tPA activities were found in patients with multiple sclerosis. The mean activity in patients with leukaemia was higher than in those with meningitis and polyradiculitis, but not encephalitis and facial paresis. Although the CSF tPA activity correlated positively with age in reference subjects, no correlation was observed in patients. Samples were qualitatively screened for both tPA and uPA activity by zymography and positive samples were quantitated. Some of the samples had quantifiable levels of uPA activity: three of seven multiple sclerosis samples, 10 of 21 samples from patients with encephalitis and five of nine leukaemic samples. The highest activities were recorded in patients with leukaemia. uPA was not detected in the CSF of the patients with meningitis, facial paresis or polyradiculitis. Conclusions-Plasminogen activator activity can be measured reliably in CSF and the assessment of tPA activity may be useful for studying the pathogenesis of neurological diseases.

Tissue-Type Plasminogen Activator Crosses the Intact Blood-Brain Barrier by Low-Density Lipoprotein Receptor–Related Protein-Mediated Transcytosis

“…In control conditions, as reported previously, 25 tPA activity is higher in the CSF than in the plasma. We show that although plasmatic tPA activity was increased at 10 minutes after the end of the injection, it returned to basal levels after 1 hour (Table).…”

Stem Cells Downregulate the Elevated Levels of Tissue Plasminogen Activator in Rats After Spinal Cord Injury

“…Although this assay does not discriminate between uPA and tPA activity, uPA is unlikely to have contributed to the increased activity observed for two reasons: (1) we performed fibrin zymography with spinal cord tissue samples from various groups and noticed prominent bands only for tPA activity (Fig. 1b); and (2) earlier reports [49,50] have demonstrated that it is the activity of tPA rather than uPA that becomes upregulated. The data are presented as mean ± SD (n = 3).…”

Tissue-Type Plasminogen Activator Is a Regulator of Monocyte Diapedesis through the Brain Endothelial Barrier

“…For example, tPA mediates activation of microglia, the resident immune cells of the CNS, upon excitotoxic injury in the brain (20). In addition, in brains of MS patients, tPA is particularly associated with inflammatory cells in the perivascular compartment and high tPA activities in the circulation correlate with the disease progression (21)(22)(23). tPA activity is also increased in areas of inflammatory damage in the animal model of MS, experimental autoimmune encephalomyelitis (EAE) (24).…”