Abstract:
The extracellular matrix (ECM) is important for both structural
integrity and functions of the brain. Matrix metalloproteinases
(MMPs) play major roles in ECM-remodeling under both
physiological and pathological conditions. Reversion-inducing
cysteine-rich protein with Kazal motifs (Reck) is a membraneanchored
MMP-regulator implicated in coordinated regulation
of pericellular proteolysis. Although patho-physiological
importance of MMPs and another group of MMP-regulators,
tissue inhibitor of metalloproteinases, in brain ischemia has
been demonstrated, little is known about the role of Reck in
this process. In this study, we found that Reck is up-regulated
in hippocampus and penumbra of subventricular zone after
transient cerebral ischemia in mice. Most of the Reck-positive
cells found at day 2 after ischemia are positive for Nestin as
well as Ki67 and localized to the CA2 region of the hippocampus.
At day 7 after ischemia, the Reck-positive cells
increased in number, extended processes, expressed the
reactive astrocyte marker GFAP and the neuronal marker
NF200, and were widely distributed in the hippocampus. In the
mutant mice carrying single functional Reck allele (Reck+/)),
tissue damage and cell death after cerebral ischemia were
augmented, the recovery of long-term potentiation in the
hippocampus was compromised, NR2C subunit of NMDA
receptor was up-regulated, gelatinolytic activity of MMPs were
up-regulated and laminin-immunoreactivity was reduced. Our
data implicate Reck in protection of ECM/tissue integrity and
promotion of functional recovery in the brain after transient
cerebral ischemia.
