In this study, we evaluated whether
propentofylline, a
methylxanthine derivative, modulates spinal glial activation and GABAergic inhibitory tone by modulation of
glutamic acid decarboxylase (GAD)(65), the
GABA synthase
enzyme, in the spinal dorsal horn following
spinal cord injury (SCI). Sprague-Dawley rats (225-250 g) were given a unilateral spinal transverse injury, from dorsal to ventral, at the T13 spinal segment. Unilateral spinal injured rats developed robust bilateral hindlimb
mechanical allodynia and hyperexcitability of spinal wide dynamic range (WDR) neurons in the lumbar enlargement (L4-L5) compared to
sham controls, which was attenuated by intrathecal (i.t.) administration of
GABA, dose-dependently (0.01, 0.1, 0.5 microg). Western blotting and immunohistochemical data demonstrated that the expression level of GAD(65)
protein significantly decreased on both sides of the lumbar dorsal horn (L4/5) after SCI (p<0.05). In addition, astrocytes and microglia showed
soma hypertrophy as determined by increased
soma area and increased GFAP and CD11b on both sides of the lumbar dorsal horn compared to
sham controls, respectively (p<0.05). Intrathecal treatment with
propentofylline (PPF 10 mM) significantly attenuated the astrocytic and microglial
soma hypertrophy and
mechanical allodynia (p<0.05). Additionally, the Western blotting and immunohistochemistry data demonstrated that i.t. treatment of PPF significantly prevented the decrease of GAD(65) expression in both sides of the lumbar dorsal horn following SCI (p<0.05). In conclusion, our present data demonstrate that
propentofylline modulates glia activation and GABAergic inhibitory tone by modulation of GAD(65)
protein expression following
spinal cord injury.