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Paper text:
in a recent issue of critical care , pan and colleagues   report the largest study to date on blood plasma - type gelsolin ( pgsn ) as a promising biomarker in subarachnoid hemorrhage ( sah ) . in a cohort of 262
well characterized sah patients and 150 control subjects , pan and colleagues found that low blood pgsn ( compared to healthy controls ) is independently predictive of poor outcome or death .
a pgsn level < 63.3  mg / l has 80.8% sensitivity and 75.1% specificity in predicting poor neurologic outcome at 6  months .
they also found an important association between the level of gelsolin and severity of sah , as measured by world federation of neurosurgical societies and fisher grading scales .
there is growing interest in the potential neuroprotective properties of gelsolin , which has two distinct isoforms .
cytoplasmic gelsolin ( cgsn ) is intracellular and ubiquitously expressed by all tissues , while pgsn has a 23 amino acid moiety targeted for extracellular secretion .
though cgsn has been implicated in numerous biological processes , including cell motility , apoptosis , and phagocytosis , the function of pgsn remains largely unknown .
since pgsn can scavenge circulating actin and lipopolysaccharide , it is thought that pgsn may dampen the deleterious pro - inflammatory effects of these circulating inflammatory mediators .
animal data have suggested a neuroprotective role for gelsolin since gelsolin - null neurons enhance cell death and gelsolin - null mice have larger infarct sizes following ischemia .
subsequent experiments showed that local infusion of pgsn decreases infarct size after ischemia , suggesting pgsn has a pivotal role in stroke .
human data have consistently shown that pgsn is decreased in severe illnesses , including sepsis , and that lower blood pgsn is associated with higher mortality . in neurovascular disorders , pgsn is decreased in both blood and cerebral spinal fluid ( csf ) in sah , and decreased blood pgsn is independently associated with mortality after intracerebral hemorrhage and ischemic stroke .
however , the fact that pgsn is associated with a wide spectrum of illnesses raises the concern that blood pgsn depletion is a non - specific marker of disease severity .
indeed , sah is the only condition where pgsn has been identified in the csf compartment itself . in sah
, novel degraded pgsn fragments were also identified in the csf - likely resulting from active digestion by matrix metalloproteinases ( mmps ) , the elevation of which is associated with worse sah outcome . in their study ,
pan and colleagues very nicely demonstrated a dose - dependent effect of pgsn on sah disease severity - the lower the level of pgsn , the more severe the sah grade and the worse the clinical outcome .
previous research has shown pgsn to be present in the csf compartment in sah and that mmps may mediate the depletion of pgsn . taken together , these studies suggest that , in the case of sah , pgsn may be more than just a non - specific marker .
it may play an active mechanistic role in sah , and could potentially serve as a therapeutic target .
exactly how does blood pgsn affect sah outcome ? where is the source of pgsn in the csf
how does the pgsn - mmp pathway facilitate inflammation and injury in the central nervous system and blood ? further targeted mechanistic studies and collaborative multicenter translational and clinical studies are needed to answer these important questions .
indeed , pgsn may not only be a novel and important clinical biomarker for sah clinical outcome , but may also be a future potential target for treatment .
cgsn : cytoplamic gelsolin ; csf : cerebral spinal fluid ; mmp : matrix metalloproteinase ; pgsn : plasma - type gelsolin ; sah : subarachnoid hemorrhage .
there is growing interest in the potential neuroprotective properties of gelsolin . 
 in particular , plasma - type gelsolin ( pgsn ) can ameliorate deleterious inflammatory response by scavenging pro - inflammatory signals such as actin and lipopolysaccharide . in a recent issue of critical care , pan and 
 colleagues report an important association between pgsn and subarachnoid hemorrhage ( sah ) disease severity , and found pgsn to be a novel and promising biomarker for sah clinical outcome . 
 previous research shows pgsn may be actively degraded by neurovascular proteases such as matrix metalloproteinases in the cerebral spinal fluid of sah patients . taken together , these results suggest that pgsn is not only a novel marker of sah clinical outcome , but may also play an active mechanistic role in sah , and potentially serve as a future therapeutic target .