  The role of neuro-inflammation in diverse, acute and chronic brain
pathologies is being increasingly recognized. Neuro-inflammation is accompanied
by increased levels of both pro- and anti-inflammatory cytokines; these have
deleterious as well as protective/reparative effects. Inflammation has varying
effects on neurogenesis and is a subject of intense contemporary interest. We
show that TNF-alpha and IFN-gamma, used concomitantly, cause apoptosis of adult
rat hippocampal progenitor/stem cells in vitro as detected by the TUNEL and MTT
assays on time scales of several hours. We have coupled Raman spectroscopy to
an optical trap to probe early changes of apoptosis in single, live neural stem
cells that have been treated with pro-inflammatory cytokines, TNF-alpha and
IFN-gamma. Changes caused by inflammation-induced denaturation of DNA are
observed in the Raman spectra that correspond to very early stages of
apoptosis, occurring on very fast time scales: as short as 10 minutes. Addition
of the anti-inflammatory cytokine IL-10 either 10-30 min before or 10-30 min
after treatment with TNF-alpha and IFN-gamma reverses the changes
substantially. Our findings imply that inflammation can induce very rapid
changes leading to cell death but that these are reversible, in the early
stages at least.
