Experimental studies have shown that many chemotherapeutic agents, when administered peripherally and in clinically relevant dosages, are associated with adverse effects on neurobiology and cognition (including 5-fluorouracil, methotrexate, doxorubicin, paclitaxel, cisplatin, BCNU and cyclophosphamide).
Moreover, more recent evidence, including the study herein, has suggested that the majority of the stem cell-mediated therapeutic effects in inflammatory CNS disorders are possibly taking place peripherally, at the level of immune relevant anatomical site, such as secondary lymphoid organs [8], [9], [36].
In addition, extensive calcification may be dislodged peripherally to produce peripheral emboli.
Due to the side effects mediated by CB1 receptor, it is clinically relevant to focus on the peripherally restricted CB1 agonists [ 57] as well as on signaling through the CB2 receptor.
Methylphenidate and dexamphetamine are sympathomimetic agents thought to act both in the central nervous system (CNS) and peripherally by enhancing dopaminergic and noradrenergic transmission through blockade of relevant transporters [ 10].
While migraine can be induced by peripherally administered CGRP (intravenous) and can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown.
Since natural frequencies reflect relevant circuit properties, TMS-evoked EEG may radically extend the window opened by peripherally evoked MEPs.
This may be due to inaccurate determination of clinically relevant immune responder status by ex vivo assays, but could also reflect local inhibition of peripherally activated immune effectors at the tumor site.
Finally, in order to confirm that VDAC1 and Pttg1 may be useful as clinically relevant biomarkers reporting on neuronal vulnerability status in vivo, we assessed protein expression levels in peripherally accessible tissue (muscle) from pre/early-symptomatic (1 month old) Ppt1 −/− and wild-type littermate control mice (n = 4 mice per genotype; Fig. 8A).
Mr. Pulsoni, 55, is himself legally blind, unable to see peripherally.
