Cerebrospinal fluid phospholipase A2 isoforms change in migraine

Objective To identify phospholipase A 2 (PLA 2 ) isoforms in human cerebrospinal fluid (CSF) and determine their changes in episodic migraine. Methods Lumbar CSF was subjected to shotgun sequencing using multidimensional LC/MS n . PLA 2 activity was determined in CSF using a liposomal fluorescent‐based activity assay in the presence or absence of PLA 2 inhibitors. PLA 2 activity was measured in paired CSF of migraine study participants in their well (H − ) compared to their headache state(H + ). Results Shotgun sequencing data revealed several PLA 2 isoforms in human lumbar CSF: groups X, XII, IV and VI PLA 2 in CSF. PLA 2 activity was significantly and reversibly inhibited by a sPLA 2 inhibitor (IC 50 =7.5 μM), and irreversibly inhibited by a cPLA 2 or iPLA 2 (IC 50 =10 μM). In paired migraine samples, V max and specific activity of PLA 2 activity was significantly higher in CSF from H + migraineurs compared with H − The Ca 2+ chelator, EDTA, only partially inhibited PLA 2 activity in CSF. Conclusions Shotgun sequencing and a combination of activity and inhibitor studies show that there are several PLA 2 isoforms in CSF: Ca 2+ dependent and Ca 2+ independent PLA 2 isoforms. In migraine, there is an increase in mainly the Ca 2+ dependent activity in H + compared with H − These data suggest that there is differential expression of PLA 2 isoforms in human CSF and these have different pathological roles. (Support: NIH, Norris Foundation).