[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 287.9/RR3
Topic: C.07.b. Neurovascular unit
Title: Tissue inhibitor of metalloproteinases protect blood brain barrier disruption in focal
cerebral ischemia
Authors: *M. FUJIMOTO, Y. TAKAGI, N. HASHIMOTO, K. NOZAKI;
Kyoto Univ., kyoto, Japan
Abstract: Enhanced matrix metalloproteinases (MMPs) can cause vasogenic edema and
hemorrhagic transformation after cerebral ischemia, and affect the extent of ischemic injury. We
hypothesized that the endogenous MMP inhibitors, tissue inhibitor of MMPs (TIMPs), were
essential to protect against blood brain barrier (BBB) disruption after ischemia by regulating the
activities of MMPs. We confirmed the transition of MMP-2 and -9, and the TIMPs family after
30 min middle cerebral artery occlusion, and elucidated the function of TIMP-1 and -2 in focal
ischemia, using TIMP-1 -/- and TIMP2 -/- mice. TIMP-1 mRNA expression was gradually
increased until 24 h after reperfusion. In TIMP-1 -/- mice, MMP-9 protein expression and
gelatinolytic activity after cerebral ischemia were significantly more augmented than those in
WT mice, and were accompanied by exacerbated BBB disruption, neuronal apoptosis, and
ischemic injury. In contrast, TIMP-2 gene deletion mice exhibited no significant difference in
MMPs expression and degree of ischemic injury, despite an increased Evans blue leakage. These
results suggest that TIMP-1 inhibits MMP-9 activity and can play a neuroprotective role in
cerebral ischemia.
Disclosures: M. Fujimoto , None; Y. Takagi, None; N. Hashimoto, None; K. Nozaki, None.
Poster
287. Blood Brain Barrier and CSF
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 287.10/RR4
Topic: E.09.c. Blood brain barrier
Title: Critical role of brain temperature in regulating blood-brain barrier permeability
Authors: *E. A. KIYATKIN 1 , H. S. SHARMA 2 ;
1 Behavioral Neurosci Br., NIDA-IRP, NIH, DHHS, Baltimore, MD; 2 Univ. Hosp., Uppsala
University, Sweden