title: Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis.
abstract: BACKGROUND
  Progranulin (PGRN) is a fundamental neurotrophic factor, and is also involved in inflammation and wound repair. PGRN may have pro- or anti-inflammatory properties, depending upon proteolysis of the anti-inflammatory parent PGRN protein and the generation of pro-inflammatory granulin peptides.
  
  
  OBJECTIVE
  Our objectives were as follows: (1) to evaluate the presence and distribution of PGRN in multiple sclerosis (MS) brain tissue, correlating it with demyelination and inflammation; (2) to evaluate cerebrospinal fluid (CSF) PGRN concentrations in patients with MS and controls, in relationship to the clinical features of the disease.
  
  
  METHODS
  Our study involved the following: (1) neuropathological study of PGRN on post-mortem tissue of 19 MS and six control brains; (2) evaluation of PGRN CSF concentration in 40 MS patients, 15 non-inflammatory controls and five inflammatory controls (viral encephalitis).
  
  
  RESULTS
  In active demyelinating lesions, PGRN was expressed on macrophages/microglia. In the normal-appearing white matter (NAWM), expression of PGRN was observed on activated microglia. PGRN was expressed by neurons and microglia in cortical lesions and in normal-appearing cortex. No expression of PGRN was observed in controls, except on neurons. PGRN CSF concentrations were significantly higher in patients with relapsing-remitting MS during relapses and in progressive MS patients, compared with relapsing-remitting MS patients during remissions and with non-inflammatory controls.
  
  
  CONCLUSIONS
  PGRN is strongly expressed in MS brains, by macrophages/microglia in active lesions, and by activated microglia in the NAWM; PGRN CSF concentrations in MS are correspondingly increased in conditions of enhanced macrophage/microglia activation, such as during relapses and in progressive MS.
authors: Department of Neuroscience, AOU S. Giovanni Battista di Torino, Turin, Italy. vercellino@libero.it
authors: Marco
authors: M
authors: Vercellino
authors: Silvia
authors: S
authors: Grifoni
authors: Alberto
authors: A
authors: Romagnolo
authors: Silvia
authors: S
authors: Masera
authors: Alessandra
authors: A
authors: Mattioda
authors: Claudia
authors: C
authors: Trebini
authors: Carlotta
authors: C
authors: Chiavazza
authors: Laura
authors: L
authors: Caligiana
authors: Elisabetta
authors: E
authors: Capello
authors: Giovanni Luigi
authors: GL
authors: Mancardi
authors: Dario
authors: D
authors: Giobbe
authors: Roberto
authors: R
authors: Mutani
authors: Maria Teresa
authors: MT
authors: Giordana
authors: Paola
authors: P
authors: Cavalla