Gallic acid attenuates blood-spinal cord barrier disruption by
inhibiting Jmjd3 expression and activation after spinal cord injury
Abstract
Background and Purpose: After spinal cord injury (SCI), blood-spinal
cord barrier (BSCB) disruption results in secondary injury including
apoptotic cell death of neurons and oligodendrocytes, thereby leads to
permanent neurological deficits. Recently, we reported that the histone
H3K27me3 demethylase Jmjd3 plays a role in regulating BSCB integrity
after SCI. Here, we investigated whether gallic acid (GA), a natural
phenolic compound that is known to be anti-inflammatory, regulates Jmjd3
expression and activation, thereby attenuates BSCB disruption following
the inflammatory response and improves functional recovery after SCI.
Experimental Approach: Rats were contused at T9 and treated with GA (50
mg/kg) via intraperitoneal injection immediately, 6 h and 12 h after
SCI, and further treated for 7 d with the same dose once a day. To
elucidate the underlying mechanism, we evaluated Jmjd3 activity and
expression, and assessed BSCB permeability by Evans blue assay after
SCI. Key Results: GA significantly inhibited Jmjd3 expression and
activation after injury both in vitro and in vivo. GA also attenuated
the expression and activation of matrix metalloprotease-9, which is well
known to disrupt the BSCB after SCI. Consistent with these findings, GA
attenuated BSCB disruption and reduced the infiltration of neutrophils
and macrophages compared with the vehicle control. Finally, GA
significantly alleviated apoptotic cell death of neurons and
oligodendrocytes and improved behavior functions. Conclusions and
Implications: Based on these data, we propose that GA can exert a
neuroprotective effect by inhibiting Jmjd3 activity and expression
followed the downregulation of matrix metalloprotease-9, eventually
attenuating BSCB disruption after SCI.